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Sample records for antiretroviral naive persons

  1. Factors influencing medication adherence beliefs and self-efficacy in persons naive to antiretroviral therapy: a multicenter, cross-sectional study.

    Science.gov (United States)

    Reynolds, Nancy R; Testa, Marcia A; Marc, Linda G; Chesney, Margaret A; Neidig, Judith L; Smith, Scott R; Vella, Stefano; Robbins, Gregory K

    2004-06-01

    It is widely recognized that adherence to antiretroviral therapy is critical to long-term treatment success, yet rates of adherence to antiretroviral medications are frequently subtherapeutic. Beliefs about antiretroviral therapy and psychosocial characteristics of HIV-positive persons naive to therapy may influence early experience with antiretroviral medication adherence and therefore could be important when designing programs to improve adherence to antiretroviral therapy. As part of a multicenter AIDS Clinical Trial Group (ACTG 384) study, 980 antiretroviral-naive subjects (82% male, 47% White, median age 36 years, and median CD4 cell count 278 cells/mm3) completed a self-administered questionnaire prior to random treatment assignment of initial antiretroviral medications. Measures of symptom distress, general health and well-being, and personal and situational factors including demographic characteristics, social support, self-efficacy, depression, stress, and current adherence to (nonantiretroviral) medications were recorded. Associations among variables were explored using correlation and regression analyses. Beliefs about the importance of antiretroviral adherence and ability to take antiretroviral medications as directed (adherence self-efficacy) were generally positive. Fifty-six percent of the participants were "extremely sure" of their ability to take all medications as directed and 48% were "extremely sure" that antiretroviral nonadherence would cause resistance, but only 37% were as sure that antiretroviral therapy would benefit their health. Less-positive beliefs about antiretroviral therapy adherence were associated with greater stress, depression, and symptom distress. More-positive beliefs about antiretroviral therapy adherence were associated with better scores on health perception, functional health, social-emotional-cognitive function, social support, role function, younger age, and higher education (r values = 0.09-0.24, all p < .001). Among

  2. Does short-term virologic failure translate to clinical events in antiretroviral-naive patients initiating antiretroviral therapy in clinical practice?

    NARCIS (Netherlands)

    Mugavero, M.J.; May, M.; Harris, R.; Saag, M.S.; Costagliola, D.; Egger, M.; Phillips, A.; Gunthard, H.F.; Dabis, F.; Hogg, R.; Wolf, F. de; Fatkenheuer, G.; Gill, M.J.; Justice, A.; Monforte, A. D'Arminio; Lampe, F.; Miro, J.M.; Staszewski, S.; Sterne, J.A.

    2008-01-01

    OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naive patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between Jan

  3. Reconstitution of naive T cells during antiretroviral treatment of HIV-infected adults is dependent on age

    NARCIS (Netherlands)

    Cohen Stuart, James; Hamann, Dörte; Borleffs, Jan; Roos, Marijke; Miedema, Frank; Boucher, Charles; de Boer, Rob

    2002-01-01

    OBJECTIVE: To determine the influence of age on the regeneration rate of naive and memory T cells in the blood of 45 adults on highly active antiretroviral therapy (HAART). METHODS: The age of the patients ranged from 25 to 57 years. Naive cells were defined as CD45RA+CD27+. Cells negative for CD45R

  4. The naive CD4+ count in HIV-1-infected patients at time of initiation of highly active antiretroviral therapy is strongly associated with the level of immunological recovery

    DEFF Research Database (Denmark)

    Michael, OG; Kirk, O; Mathiesen, Lars Reinhardt

    2002-01-01

    Current antiretroviral therapy can induce considerable, sustained viral suppression followed by immunological recovery, in which naive CD4 + cells are important. Long-term immunological recovery was investigated during the first 3 y of highly active antiretroviral therapy (HAART) in 210 HIV-1...... was sustained. There was no association between plasma viral load and the increase in naive CD4 + cell count. Importantly, baseline naive CD4 + cell count was significantly associated with the change in naive CD4 + cell count, suggesting that the naive cell count at baseline does influence the immunological...

  5. Short Communication: Transmitted HIV Drug Resistance in Antiretroviral-Naive Pregnant Women in North Central Nigeria

    Science.gov (United States)

    Sagay, Atiene S.; Chaplin, Beth; Chebu, Philippe; Musa, Jonah; Okpokwu, Jonathan; Hamel, Donald J.; Pam, Ishaya C.; Agbaji, Oche; Samuels, Jay; Meloni, Seema; Sankale, Jean-Louis; Okonkwo, Prosper; Kanki, Phyllis

    2014-01-01

    Abstract The World Health Organization (WHO) recommends periodic surveillance of transmitted drug resistance (TDR) in communities in which antiretroviral therapy (ART) has been scaled-up for greater than 3 years. We conducted a survey of TDR mutations among newly detected HIV-infected antiretroviral (ARV)-naive pregnant women. From May 2010 to March 2012, 38 ARV-naive pregnant women were recruited in three hospitals in Jos, Plateau state, north central Nigeria. Eligible subjects were recruited using a modified version of the binomial sequential sampling technique recommended by WHO. HIV-1 genotyping was performed and HIV-1 drug resistance mutations were characterized according to the WHO 2009 surveillance drug resistance mutation (SDRM) list. HIV subtypes were determined by phylogenetic analysis. The women's median age was 25.5 years; the median CD4+ cell count was 317 cells/μl and the median viral load of 16 was 261 copies/ml. Of the 38 samples tested, 34 (89%) were successfully genotyped. The SDRM rate was <5% for all ART drug classes, with 1/34 (2.9%) for NRTIs/NNRTIs and none for protease inhibitors 0/31 (0%). The specific SDRMs detected were M41L for nucleoside reverse transcriptase inhibitors (NRTIs) and G190A for nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIV-1 subtypes detected were CRF02_AG (38.2%), G′ (41.2%), G (14.7%), CRF06-CPX (2.9%), and a unique AG recombinant form (2.9%). The single ARV-native pregnant woman with SDRMs was infected with HIV-1 subtype G′. Access to ART has been available in the Jos area for over 8 years. The prevalence of TDR lower than 5% suggests proper ART administration, although continued surveillance is warranted. PMID:24164431

  6. Risk of discontinuation of nevirapine due to toxicities in antiretroviral-naive and -experienced HIV-infected patients with high and low CD4+ T-cell counts

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Staszewski, Schlomo; Weber, Rainer;

    2007-01-01

    It is unknown whether the increased risk of toxicities in antiretroviral-naive HIV-infected patients initiating nevirapine-based (NVPc) combination antiretroviral therapy (cART) with high CD4+ T-cell counts is also observed when NVPc is initiated in cARTexperienced patients.......It is unknown whether the increased risk of toxicities in antiretroviral-naive HIV-infected patients initiating nevirapine-based (NVPc) combination antiretroviral therapy (cART) with high CD4+ T-cell counts is also observed when NVPc is initiated in cARTexperienced patients....

  7. Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.

    Science.gov (United States)

    Pérez, Lissette; Kourí, Vivian; Alemán, Yoan; Abrahantes, Yeisel; Correa, Consuelo; Aragonés, Carlos; Martínez, Orlando; Pérez, Jorge; Fonseca, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Dekeersmaeker, Nathalie; Imbrechts, Stijn; Beheydt, Gertjan; Vinken, Lore; Soto, Yudira; Álvarez, Alina; Vandamme, Anne-Mieke; Van Laethem, Kristel

    2013-06-01

    In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the

  8. Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults : 48-week results from the antiretroviral regimen evaluation study (ARES)

    NARCIS (Netherlands)

    Lowe, SH; Wensing, AMJ; Hassink, EAM; ten Kate, RW; Richter, C; Schreij, G; Koopmans, PP; Juttmann, J.; van der Tweel, I.; Lange, JMA; Borleffs, JCC

    2005-01-01

    Background: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. Method: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida

  9. Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults: 48-week results from the Antiretroviral Regimen Evaluation Study (ARES).

    NARCIS (Netherlands)

    Lowe, S.H.; Wensing, B.M.; Hassink, E.A.M.; Kate, R.W. ten; Richter, C.; Schreij, G.; Koopmans, P.P.; Juttmann, J.R.; Tweel, I. van de; Lange, J.M.A.; Borleffs, J.C.

    2005-01-01

    BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. METHOD: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida

  10. Renal function, urinalysis abnormalities and correlates among HIV-infected Cameroonians naive to antiretroviral therapy.

    Science.gov (United States)

    FolefackKaze, Francois; Kengne, Andre-Pascal; Pefura Yone, Eric Walter; NdamFemben, Nelly Sandra; Ashuntantang, Gloria

    2013-11-01

    As per guidelines and recommendations, screening for renal diseases should be performed at the time of diagnosis of human immuno-deficiency virus (HIV) infection; however, this remains largely unimplemented in many settings across Sub-Saharan Africa. We evaluated the renal function, urinalysis abnormalities and their correlates in HIV-infected individuals who were naïve to highly active antiretroviral therapy (HAART). This was a cross-sectional study of 2 months' duration involving 104 HIV-infected outpatients naive to HAART (71 women, 68%) attending the HIV clinic of the Yaoundé General Hospital in Cameroon. Renal and urinalysis parameters were measured and the Student t-test and Fischer exact test were used to compare the groups of participants. The mean age and CD4 count were, respectively, 35 ± 10.7 years and 305 ± 202/mL. Fifty-six (54%) patients presented with stages 3 and 4 of HIV infection. Forty-three (41%) patients had urinalysis abnormalities, including proteinuria (36%), leukocyturia (13%) and hematuria (12%). Proteinuria was associated with increased age, advanced stage of HIV infection, decreased CD4 count, hematuria and renal failure (P HIV infection, respectively (P = 0.04). The mean estimated glomerular filtration (eGFR) rate was 100.2 ± 32.7 mL/min; three (3%) patients had renal failure (eGFR patients had reduced kidney function 60 ≤eGFR ≤90 mL/min. There was a high prevalence of decreased kidney function and proteinuria among Cameroonian HIV-infected patients naïve to HAART. Indicators of the severity of HIV infection, including advanced stage and low CD4 count, were associated with urinalysis abnormalities.

  11. Low immunologic response to highly active antiretroviral therapy in naive vertically human immunodeficiency virus type 1-infected children with severe immunodeficiency.

    Science.gov (United States)

    Resino, Salvador; Alvaro-Meca, Alejandro; de José, Maria Isabel; Martin-Fontelos, Pablo; Gutiérrez, Maria Dolores Gurbindo; Léon, Juan Antonio; Ramos, José Tomás; Ciria, Luis; Muñoz-Fernández, Maria Angeles

    2006-04-01

    We conducted a retrospective study to analyze the CD4 recovery of naive vertically human immunodeficiency virus-infected children with severe immunodeficiency who were followed up during at least 4 years of receiving highly active antiretroviral therapy (HAART). Children with baseline CD4 of or =25% after the 4th year on HAART. We conclude that starting HAART after severe immunosuppression of naive HIV-infected children may not be effective for recovery of normal %CD4.

  12. Factors associated with short-term changes in HIV viral load and CD4+ cell count in antiretroviral-naive individuals

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2014-01-01

    OBJECTIVES: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4(+) cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression. DESIGN: An observational cohort...

  13. Tissue-resident macrophages can contain replication-competent virus in antiretroviral-naive, SIV-infected Asian macaques

    Science.gov (United States)

    DiNapoli, Sarah R.; Ortiz, Alexandra M.; Wu, Fan; Matsuda, Kenta; Hirsch, Vanessa M.; Knox, Kenneth

    2017-01-01

    SIV DNA can be detected in lymphoid tissue–resident macrophages of chronically SIV-infected Asian macaques. These macrophages also contain evidence of recently phagocytosed SIV-infected CD4+ T cells. Here, we examine whether these macrophages contain replication-competent virus, whether viral DNA can be detected in tissue-resident macrophages from antiretroviral (ARV) therapy–treated animals and humans, and how the viral sequences amplified from macrophages and contemporaneous CD4+ T cells compare. In ARV-naive animals, we find that lymphoid tissue–resident macrophages contain replication-competent virus if they also contain viral DNA in ARV-naive Asian macaques. The genetic sequence of the virus within these macrophages is similar to those within CD4+ T cells from the same anatomic sites. In ARV-treated animals, we find that viral DNA can be amplified from lymphoid tissue–resident macrophages of SIV-infected Asian macaques that were treated with ARVs for at least 5 months, but we could not detect replication-competent virus from macrophages of animals treated with ARVs. Finally, we could not detect viral DNA in alveolar macrophages from HIV-infected individuals who received ARVs for 3 years and had undetectable viral loads. These data demonstrate that macrophages can contain replication-competent virus, but may not represent a significant reservoir for HIV in vivo.

  14. Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8+ T Cells

    Directory of Open Access Journals (Sweden)

    Kellie N. Smith

    2016-05-01

    Full Text Available Curing HIV-1 infection will require elimination of persistent cellular reservoirs that harbor latent virus in the face of combination antiretroviral therapy (cART. Proposed immunotherapeutic strategies to cure HIV-1 infection include enhancing lysis of these infected cells by cytotoxic T lymphocytes (CTL. A major challenge in this strategy is overcoming viral immune escape variants that have evaded host immune control. Here we report that naive CD8+ T cells from chronic HIV-1-infected participants on long-term cART can be primed by dendritic cells (DC. These DC must be mature, produce high levels of interleukin 12p70 (IL-12p70, be responsive to CD40 ligand (CD40L, and be loaded with inactivated, autologous HIV-1. These DC-primed CD8+ T cell responders produced high levels of gamma interferon (IFN-γ in response to a broad range of both conserved and variable regions of Gag and effectively killed CD4+ T cell targets that were either infected with the autologous latent reservoir-associated virus or loaded with autologous Gag peptides. In contrast, HIV-1-specific memory CD8+ T cells stimulated with autologous HIV-1-loaded DC produced IFN-γ in response to a narrow range of conserved and variable Gag peptides compared to the primed T cells and most notably, displayed significantly lower cytolytic function. Our findings highlight the need to selectively induce new HIV-1-specific CTL from naive precursors while avoiding activation of existing, dysfunctional memory T cells in potential curative immunotherapeutic strategies for HIV-1 infection.

  15. Efficacy, Safety and Pharmacokinetics of Once-Daily Saquinavir Soft-Gelatin Capsule/Ritonavir in Antiretroviral-Naive, HIV-Infected Patients

    OpenAIRE

    Julio, Montaner SG; Schutz, Malte; Schwartz, Robert; Jayaweera, Dushyantha T; Burnside, Alfred F; Walmsley, Sharon; Saag, Michael S.

    2006-01-01

    Context Once-daily HIV treatment regimens are being used in clinical practice with the objective of improving patient acceptance and adherence. Objective To evaluate the efficacy and safety of saquinavir-soft-gelatin capsule (SGC)/ritonavir combination (1600 mg/100 mg) vs efavirenz (600 mg) both once daily and combined with 2 nucleoside analogs twice daily. Setting Twenty-six centers in the United States, Canada, and Puerto Rico. Patients A total of 171 antiretroviral naive HIV-infected indiv...

  16. Efficacy, Safety and Pharmacokinetics of Once-Daily Saquinavir Soft-Gelatin Capsule/Ritonavir in Antiretroviral-Naive, HIV-Infected Patients

    OpenAIRE

    Julio SG Montaner; Schutz Malte; Schwartz Robert; Jayaweera Dushyantha T; Burnside Alfred F; Walmsley Sharon; Saag Michael S

    2006-01-01

    Abstract Context Once-daily HIV treatment regimens are being used in clinical practice with the objective of improving patient acceptance and adherence. Objective To evaluate the efficacy and safety of saquinavir-soft-gelatin capsule (SGC)/ritonavir combination (1600 mg/100 mg) vs efavirenz (600 mg) both once daily and combined with 2 nucleoside analogs twice daily. Setting Twenty-six centers in the United States, Canada, and Puerto Rico. Patients A total of 171 antiretroviral naive HIV-infec...

  17. Genotypic Characterization of Human Immunodeficiency Virus Type 1 Derived from Antiretroviral Therapy-Naive Individuals Residing in Sorong, West Papua.

    Science.gov (United States)

    Witaningrum, Adiana Mutamsari; Kotaki, Tomohiro; Khairunisa, Siti Qamariyah; Yunifiar M, Muhammad Qushai; Indriati, Dwi Wahyu; Bramanthi, Rendra; Nasronudin; Kameoka, Masanori

    2016-08-01

    Papua and West Papua provinces have the highest prevalence rate of human immunodeficiency virus type 1 (HIV-1) infection in Indonesia; however, data on the molecular epidemiology of HIV-1 are limited. We conducted a genotypic study on HIV-1 genes derived from antiretroviral therapy-naive individuals residing in Sorong, West Papua. HIV-1 genomic fragments were amplified from 43 peripheral blood samples, and sequencing analysis of the genes was carried out. Of the 43 samples, 41 protease (PR), 31 reverse transcriptase (RT), 26 gag, and 25 env genes were sequenced. HIV-1 subtyping revealed that CRF01_AE (48.8%, 21/43) and subtype B (41.9%, 18/43) were the major subtypes prevalent in the region, whereas other recombinant forms were also detected. Major drug resistance-associated mutations for PR inhibitors were not detected; however, mutations for the RT inhibitors, A62V and E138A, appeared in a few samples, indicating the possible emergence of transmitted HIV-1 drug resistance in Sorong, West Papua.

  18. Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs

    DEFF Research Database (Denmark)

    Kolte, L.; Gaardbo, J.C.; Skogstrand, K.;

    2009-01-01

    This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive...

  19. Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.

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    Hubert Barennes

    Full Text Available INTRODUCTION: In resource limited settings, patients entering an antiretroviral therapy (ART program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. METHODS: This retrospective study, conducted in 2010-2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia assessed virological failure (VF rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF (>1,000 copies/ml underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. RESULTS: On a total of 209 patients, 164 (78.4% were naive and 45 (21.5% were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30-194 and 279 cells/mm3 (IQR: 103-455 (p<0.001, respectively. Twenty seven patients (12.9% exhibited VF (95% CI: 8.6-18.2%, including 10 naive (10/164, 6.0% and 17 pre-treated (17/45, 37.8% patients (p<0.001. Among these viremic patients, twenty-two (81.4% were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3% harbored ≥1 drug resistance mutations (DRMs whereas 3 (all belonging to pre-treated patients harbored wild-types viruses. The most frequent DRMs were M184V (86.3%, K103N (45.5% and thymidine analog mutations (TAMs (40.9%. Two (13.3% pre-treated patients harbored viruses that showed a multi-nucleos(tide resistance including Q151M, K65R, E33A/D, E44A/D mutations. CONCLUSION: In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre

  20. Personality matters: individual variation in reactions of naive bird predators to aposematic prey.

    Science.gov (United States)

    Exnerová, Alice; Svádová, Katerina Hotová; Fucíková, Eva; Drent, Pieter; Stys, Pavel

    2010-03-01

    Variation in reactions to aposematic prey is common among conspecific individuals of bird predators. It may result from different individual experience but it also exists among naive birds. This variation may possibly be explained by the effect of personality--a complex of correlated, heritable behavioural traits consistent across contexts. In the great tit (Parus major), two extreme personality types have been defined. 'Fast' explorers are bold, aggressive and routine-forming; 'slow' explorers are shy, non-aggressive and innovative. Influence of personality type on unlearned reaction to aposematic prey, rate of avoidance learning and memory were tested in naive, hand-reared great tits from two opposite lines selected for exploration (slow against fast). The birds were subjected to a sequence of trials in which they were offered aposematic adult firebugs (Pyrrhocoris apterus). Slow birds showed a greater degree of unlearned wariness and learned to avoid the firebugs faster than fast birds. Although birds of both personality types remembered their experience, slow birds were more cautious in the memory test. We conclude that not only different species but also populations of predators that differ in proportions of personality types may have different impacts on survival of aposematic insects under natural conditions.

  1. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1

    DEFF Research Database (Denmark)

    Raffi, François; Babiker, Abdel G; Richert, Laura;

    2014-01-01

    BACKGROUND: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. METHODS: Between August, 2010, and...

  2. Effect of Micronutrient and Probiotic Fortified Yogurt on Immune-Function of Anti-Retroviral Therapy Naive HIV Patients  

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    J. Dik F. Habbema

    2011-10-01

    Full Text Available Background: Micronutrient supplementation has been shown to reduce the progression of HIV but does not have an effect on the intestinal barrier or the intestinal microbiota of HIV patients. Studies have suggested that probiotics could potentially complement micronutrients in preserving the immune-function of HIV patients. Objective: Assess the impact of micronutrient supplemented probiotic yogurt on the immune function of HIV patients. Design: We performed a randomized, double blind, controlled trial with CD4 count as primary outcome among HIV patients naïve to anti-retroviral treatment. Secondary outcomes included hematological parameters, incidence of diarrhea and clinical symptoms. A total of 112 HIV patients were randomized to receive a micronutrient fortified yogurt with (n = 55 or without additional probiotic Lactobacillus rhamnosus GR-1 (n = 57 for four weeks. Results: An average decline in CD4 count of −70 cells/μL (95% CI: −154 to −15 was observed in the micronutrient, probiotic group versus a decrease of −63 cells/μL (95% CI: −157 to −30 in the micronutrient control group (p = 0.9. Additional probiotic supplementation was well tolerated and not associated with adverse events. No difference between groups was detected in incidence of diarrhea or clinical symptoms. An improvement of hemoglobin levels was observed for all subjects, based upon a mean difference from baseline of 1.4 g/L (SD = 6 (p = 0.02. Conclusion: The addition of probiotics to a micronutrient fortified yogurt was well tolerated by HIV patients but was not associated with a further increase in CD4 count after one month.

  3. Identification of Immunogenic Cytotoxic T Lymphocyte Epitopes Containing Drug Resistance Mutations in Antiretroviral Treatment-Naive HIV-Infected Individuals.

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    Juan Blanco-Heredia

    Full Text Available Therapeutic HIV vaccines may prove helpful to intensify antiretroviral treatment (ART efficacy and may be an integral part of future cure strategies.We examined IFN-gamma ELISpot responses to a panel of 218 HIV clade B consensus-based HIV protease-reverse transcriptase peptides, designed to mimic previously described and predicted cytotoxic T lymphocyte epitopes overlapping drug resistance (DR positions, that either included the consensus sequence or the DR variant sequence, in 49 ART-naïve HIV-infected individuals. Next generation sequencing was used to assess the presence of minority DR variants in circulating viral populations.Although a wide spectrum of differential magnitudes of response to DR vs. WT peptide pairs was observed, responses to DR peptides were frequent and strong in the study cohort. No difference between the median magnitudes of response to DR vs. WT peptides was observed. Interestingly, of the 22 peptides that were recognized by >15% of the participants, two-thirds (64% corresponded to DR peptides. When analysing responses per peptide pair per individual, responses to only WT (median 4 pairs/individual or DR (median 6 pairs/individual were more common than responses to both WT and DR (median 2 pairs/individual; p<0.001. While the presence of ELISpot responses to WT peptides was frequently associated with the presence of the corresponding peptide sequence in the patient's virus (mean 68% of cases, responses to DR peptides were generally not associated with the presence of DR mutations in the viral population, even at low frequencies (mean 1.4% of cases; p = 0.0002.Our data suggests that DR peptides are frequently immunogenic and raises the potential benefit of broadening the antigens included in a therapeutic vaccine approach to immunogenic epitopes containing common DR sequences. Further studies are needed to assess the quality of responses elicited by DR peptides.

  4. Efficacy, Safety and Pharmacokinetics of Once-Daily Saquinavir Soft-Gelatin Capsule/Ritonavir in Antiretroviral-Naive, HIV-Infected Patients

    Directory of Open Access Journals (Sweden)

    Julio Montaner SG

    2006-05-01

    Full Text Available Abstract Context Once-daily HIV treatment regimens are being used in clinical practice with the objective of improving patient acceptance and adherence. Objective To evaluate the efficacy and safety of saquinavir-soft-gelatin capsule (SGC/ritonavir combination (1600 mg/100 mg vs efavirenz (600 mg both once daily and combined with 2 nucleoside analogs twice daily. Setting Twenty-six centers in the United States, Canada, and Puerto Rico. Patients A total of 171 antiretroviral naive HIV-infected individuals were enrolled in a 48-week, phase 3, open-label, randomized study. Main Outcome Measure Proportion of patients with HIV-RNA levels Results In the primary intent-to-treat population at week 48, 51% (38/75 and 71% (55/77 of patients in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, achieved HIV-RNA suppression P = .5392, 95% 1-sided confidence interval [CI] = -33.5%. In the on-treatment (OT population, 73% (38/52 and 93% (54/58 of patients in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, had effective viral suppression P = .5015, 95% 1-sided CI = -33.4%. Mean CD4+ cell counts increased by 239 and 204 cells/microliters (mcL, in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, in the OT analysis (P = .058. Both regimens were reasonably well tolerated, although more gastrointestinal adverse events were reported with saquinavir-SGC/ritonavir. Pharmacokinetic profiles in 6 patients showed an observed median Cmin at 24 hours of 429 ng/mL (range, 68-1750 ng/mL. Conclusion Once-daily efavirenz was statistically superior to once-daily saquinavir-SGC/ritonavir. Gastrointestinal adverse effects were commonly associated with treatment failure in the saquinavir-SGC/ritonavir arm of the study.

  5. Personality matters: individual variation in reactions of naive bird predators to aposematic prey

    NARCIS (Netherlands)

    Exnerová, A.; Hotova Svadova, K.; Fucikova, E.; Drent, P.; Stys, P.

    2010-01-01

    Variation in reactions to aposematic prey is common among conspecific individuals of bird predators. It may result from different individual experience but it also exists among naive birds. This variation may possibly be explained by the effect of personality—a complex of correlated, heritable behav

  6. Antidepressant Treatment and Adherence to Antiretroviral Medications among Privately Insured Persons with HIV/AIDS

    OpenAIRE

    Akincigil, Ayse; Wilson, Ira; Walkup, James T.; Michele J Siegel; Huang, Cecilia; Crystal, Stephen

    2011-01-01

    In order to examine relationships between depression treatments (antidepressant and/or psychotherapy utilization) and adherence to antiretroviral therapy (ART), we conducted a retrospective analysis of medical and pharmacy insurance claims for privately insured persons living with HIV/AIDS (PLWHA) diagnosed with depression (n=1,150). Participants were enrolled in 80 insurance plans from all 50 states. Adherence was suboptimal. Depression treatment initiators were significantly more likely to ...

  7. Renal function declines more in tenofovir- than abacavir-based antiretroviral therapy in low-body weight treatment-naive patients with HIV infection.

    Directory of Open Access Journals (Sweden)

    Takeshi Nishijima

    Full Text Available OBJECTIVE: To compare the rate of decline of renal function in tenofovir- and abacavir-based antiretroviral therapy (ART in low-body weight treatment-naïve patients with HIV infection. DESIGN: We conducted a single-center retrospective cohort study of 503 Japanese patients who commenced on either tenofovir- or abacavir-based initial ART. METHODS: The incidence of renal dysfunction, defined as more than 25% fall in estimated glomerular filtration rate (eGFR from the baseline, was determined in each group. The effect of tenofovir on renal dysfunction was estimated by univariate and multivariate Cox hazards models as the primary exposure. Changes in eGFR until 96 weeks were estimated in both groups with a repeated measures mixed model. RESULTS: The median body weight of the cohort was 64 kg. The estimated incidence of renal dysfunction in the tenofovir and the abacavir arm was 9.84 per 100 and 4.55 per 100 person-years, respectively. Tenofovir was significantly associated with renal dysfunction by univariate and multivariate analysis (HR = 1.747; 95% CI, 1.152-2.648; p = 0.009 (adjusted HR = 2.080; 95% CI, 1.339-3.232; p68 kg: adjusted HR = 0.997; 95%CI, 0.318-3.121; p = 0.995. The fall in eGFR was significantly greater in the tenofovir arm than the abacavir arm after starting ART (p = 0.003. CONCLUSION: The incidence of renal dysfunction in low body weight patients treated with tenofovir was twice as high as those treated with abacavir. Close monitoring of renal function is recommended for patients with small body weight especially those with baseline body weight <60 kg treated with tenofovir.

  8. Response to combination antiretroviral therapy: variation by age

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    OBJECTIVE: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. SUBJECTS:: Forty-nine thousand nine hundred and twenty-one antiretroviral......-naive individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and immunological...

  9. Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Cambiano, Valentina; Miners, Alec;

    2014-01-01

    BACKGROUND: With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial...

  10. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study

    DEFF Research Database (Denmark)

    Lundgren, Jens; Emery, Sean; Neuhaus, Jacqueline A;

    2008-01-01

    BACKGROUND: The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group...

  11. Antiretroviral Agents Used by HIV-Uninfected Persons for Prevention: Pre- and Postexposure Prophylaxis

    Science.gov (United States)

    Grant, Robert M.

    2010-01-01

    Prophylactic use of antimicrobial agents and microbicides has been proven for many infections, including surgical, gastrointestinal, upper respiratory, and meningococcal infections. Antiretroviral therapy for pregnant women prevents mother-to-child transmission of human immunodeficiency virus (HIV), which has become rare in settings where access to therapy is widespread. Postexposure prophylaxis after needlestick injury or significant sexual exposure is recommended on the basis of animal studies and case-control observational studies, although use of these interventions is limited to those who recognize exposure, have access, and have the power to use the interventions. Clinical trials are evaluating whether regular or preexposure use of antiretroviral therapy provides additional protection for persons at high risk of infection who are also offered standard prevention care, including HIV testing, counseling, condoms, and management of sexually transmitted infections. Trials are evaluating topical or oral use. Concerns have arisen with regard to optimal dosing strategies, costs, access, drug resistance, risk behavior, and the role of communities. Future implementation, if warranted, will be guided by the results of clinical trials in progress and engagement of communities exposed to HIV. PMID:20397962

  12. Antidepressant treatment and adherence to antiretroviral medications among privately insured persons with HIV/AIDS.

    Science.gov (United States)

    Akincigil, Ayse; Wilson, Ira B; Walkup, James T; Siegel, Michele J; Huang, Cecilia; Crystal, Stephen

    2011-11-01

    In order to examine relationships between depression treatments (antidepressant and/or psychotherapy utilization) and adherence to antiretroviral therapy (ART), we conducted a retrospective analysis of medical and pharmacy insurance claims for privately insured persons living with HIV/AIDS (PLWHA) diagnosed with depression (n = 1,150). Participants were enrolled in 80 insurance plans from all 50 states. Adherence was suboptimal. Depression treatment initiators were significantly more likely to be adherent to ART than the untreated. We did not observe an association between psychotherapy utilization and ART adherence, yet given the limitations of the data (e.g., there is no information on types of psychological treatment and its targets), the lack of association should not be interpreted as lack of efficacy.

  13. HIV-1 transmission patterns in antiretroviral therapy-naive, HIV-infected North Americans based on phylogenetic analysis by population level and ultra-deep DNA sequencing.

    Directory of Open Access Journals (Sweden)

    Lisa L Ross

    Full Text Available Factors that contribute to the transmission of human immunodeficiency virus type 1 (HIV-1, especially drug-resistant HIV-1 variants remain a significant public health concern. In-depth phylogenetic analyses of viral sequences obtained in the screening phase from antiretroviral-naïve HIV-infected patients seeking enrollment in EPZ108859, a large open-label study in the USA, Canada and Puerto Rico (ClinicalTrials.gov NCT00440947 were examined for insights into the roles of drug resistance and epidemiological factors that could impact disease dissemination. Viral transmission clusters (VTCs were initially predicted from a phylogenetic analysis of population level HIV-1 pol sequences obtained from 690 antiretroviral-naïve subjects in 2007. Subsequently, the predicted VTCs were tested for robustness by ultra deep sequencing (UDS using pyrosequencing technology and further phylogenetic analyses. The demographic characteristics of clustered and non-clustered subjects were then compared. From 690 subjects, 69 were assigned to 1 of 30 VTCs, each containing 2 to 5 subjects. Race composition of VTCs were significantly more likely to be white (72% vs. 60%; p = 0.04. VTCs had fewer reverse transcriptase and major PI resistance mutations (9% vs. 24%; p = 0.002 than non-clustered sequences. Both men-who-have-sex-with-men (MSM (68% vs. 48%; p = 0.001 and Canadians (29% vs. 14%; p = 0.03 were significantly more frequent in VTCs than non-clustered sequences. Of the 515 subjects who initiated antiretroviral therapy, 33 experienced confirmed virologic failure through 144 weeks while only 3/33 were from VTCs. Fewer VTCs subjects (as compared to those with non-clustering virus had HIV-1 with resistance-associated mutations or experienced virologic failure during the course of the study. Our analysis shows specific geographical and drug resistance trends that correlate well with transmission clusters defined by HIV sequences of similarity

  14. Effect of granulocyte colony-stimulating factor (G-CSF) in human immunodeficiency virus-infected patients: increase in numbers of naive CD4 cells and CD34 cells makes G-CSF a candidate for use in gene therapy or to support antiretroviral therapy

    DEFF Research Database (Denmark)

    Nielsen, S D; Afzelius, P; Dam-Larsen, S

    1998-01-01

    The potential of granulocyte colony-stimulating factor (G-CSF) to mobilize CD4 cells and/or CD34 cells for use in gene therapy or to support antiretroviral therapy was examined. Ten human immunodeficiency virus-infected patients were treated with G-CSF (300 microg/day) for 5 days. Numbers of CD4....... Furthermore, the fraction of naive CD4 cells increased. These findings have implications for the design of immunotherapy or gene therapy protocols....

  15. Randomized, double-blind trial comparing indinavir alone, zidovudine alone and indinavir plus zidovudine in antiretroviral therapy-naive hiv-infected individuals with CD4 cell counts between 50 and 250/mm3

    Directory of Open Access Journals (Sweden)

    LEWI David S.

    2000-01-01

    Full Text Available Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h, zidovidine alone (200 mg q8h or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0.0001. Over a median follow-up of 52 weeks (up to 99 weeks, percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.

  16. Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naive to Antiretroviral Therapy: A Pilot Randomized Trial.

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    Sergio Serrano-Villar

    2016-01-01

    Full Text Available Whether initiation of antiretroviral therapy (ART regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6, lipoteichoic acid (LTA, soluble CD14 (sCD14 and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively, with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease

  17. Prevalence of Hypertension in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART Compared with HAART-Naive Patients at the Limbe Regional Hospital, Cameroon.

    Directory of Open Access Journals (Sweden)

    Christian Akem Dimala

    Full Text Available Highly active antiretroviral therapy (HAART has greatly reduced the morbidity and mortality of HIV/AIDS patients but has also been associated with increased metabolic complications and cardiovascular diseases. Data on the association between HAART and hypertension (HTN in Africa are scarce.Primarily to compare the prevalence of HTN in HIV/AIDS patients on HAART and HAART-naïve patients in Limbe, Cameroon; and secondarily to assess other socio-demographic and clinical factors associated with HTN in this population.A cross-sectional study was conducted at the Limbe Regional Hospital HIV treatment center between April and June 2013, involving 200 HIV/AIDS patients (100 on first-line HAART regimens for at least 12 months matched by age and sex to 100 HAART-naïve patients. HTN was defined as a systolic blood pressure (BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg.The prevalence of HTN in patients on HAART was twice (38%; 95% CI: 28.5-48.3 that of the HAART-naïve patients (19%; 95% CI, 11.8-28.1, p = 0.003. In multivariate analyses adjusted for age, gender, smoking, family history of HTN, and BMI-defined overweight, HAART was associated with HTN, the adjusted odds ratio of the HAART-treated versus HAART-naïve group was 2.20 (95% CI: 1.07-4.52, p = 0.032. HTN was associated with older age and male gender, in the HAART group and with BMI-defined overweight in the HAART-naïve group.The prevalence of hypertension in HIV/AIDS patients in Limbe stands out to be elevated, higher in patients on HAART compared to those not on treatment. Blood pressure and cardiovascular risk factors should be routinely monitored. Other factors such as diet, weight control and physical exercise should also be considered.

  18. Longitudinal Analysis of CCR5 and CXCR4 Usage in a Cohort of Antiretroviral Therapy-Naive Subjects with Progressive HIV-1 Subtype C Infection.

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    Martin R Jakobsen

    Full Text Available HIV-1 subtype C (C-HIV is responsible for most HIV-1 cases worldwide. Although the pathogenesis of C-HIV is thought to predominantly involve CCR5-restricted (R5 strains, we do not have a firm understanding of how frequently CXCR4-using (X4 and R5X4 variants emerge in subjects with progressive C-HIV infection. Nor do we completely understand the molecular determinants of coreceptor switching by C-HIV variants. Here, we characterized a panel of HIV-1 envelope glycoproteins (Envs (n = 300 cloned sequentially from plasma of 21 antiretroviral therapy (ART-naïve subjects who experienced progression from chronic to advanced stages of C-HIV infection, and show that CXCR4-using C-HIV variants emerged in only one individual. Mutagenesis studies and structural models suggest that the evolution of R5 to X4 variants in this subject principally involved acquisition of an "Ile-Gly" insertion in the gp120 V3 loop and replacement of the V3 "Gly-Pro-Gly" crown with a "Gly-Arg-Gly" motif, but that the accumulation of additional gp120 "scaffold" mutations was required for these V3 loop changes to confer functional effects. In this context, either of the V3 loop changes could confer possible transitional R5X4 phenotypes, but when present together they completely abolished CCR5 usage and conferred the X4 phenotype. Our results show that the emergence of CXCR4-using strains is rare in this cohort of untreated individuals with advanced C-HIV infection. In the subject where X4 variants did emerge, alterations in the gp120 V3 loop were necessary but not sufficient to confer CXCR4 usage.

  19. The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults

    Science.gov (United States)

    Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H.; García, Felipe.; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L.; Mounzer, Karam; Swindells, Susan; Baxter, John D.; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François

    2016-01-01

    Abstract The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): −0.088; 0.235]), or F4/AS01B_3 and control group (−0.096 log10 copies/mL [97.5% CI: −0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4+ T-cell responses, but did not reduce HIV-1 VL, impact CD4+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events. PMID:26871794

  20. HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes.

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    Yaxelis Mendoza

    Full Text Available The use of antiretroviral therapy in HIV infected subjects prevents AIDS-related illness and delayed occurrence of death. In Panama, rollout of ART started in 1999 and national coverage has reached 62.8% since then. The objective of this study was to determine the level and patterns of acquired drug resistance mutations of clinical relevance (ADR-CRM and surveillance drug resistance mutations (SDRMs from 717 HIV-1 pol gene sequences obtained from 467 ARV drug-experienced and 250 ARV drug-naïve HIV-1 subtypes B infected subjects during 2007-2013, respectively. The overall prevalence of SDRM and of ADR-CRM during the study period was 9.2% and 87.6%, respectively. The majority of subjects with ADR-CRM had a pattern of mutations that confer resistance to at least two classes of ARV inhibitors. The non-nucleoside reverse transcriptase inhibitor (NNRTI mutations K103N and P225H were more prevalent in both ARV drug-naïve and ARV drug-experienced subjects. The nucleoside reverse transcriptase inhibitor (NRTI mutation M184V was more frequent in ARV drug-experienced individuals, while T215YFrev and M41L were more frequent in ARV drug-naïve subjects. Prevalence of mutations associated to protease inhibitors (PI was lower than 4.1% in both types of subjects. Therefore, there is a high level of resistance (>73% to Efavirenz/Nevirapine, Lamivudine and Azidothymidine in ARV drug-experienced subjects, and an intermediate to high level of resistance (5-10% to Efavirenz/Nevirapine in ARV drug-naïve subjects. During the study period, we observed an increasing trend in the prevalence of ADR-CRM in subjects under first-line schemes, but not significant changes in the prevalence of SDRM. These results reinforce the paramount importance of a national surveillance system of ADR-CRM and SDRM for national management policies of subjects living with HIV.

  1. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons

    DEFF Research Database (Denmark)

    Kovari, Helen; Sabin, Caroline A; Ledergerber, Bruno;

    2016-01-01

    Background.  Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods.  Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without...... a consistent association between tenofovir and cLEE emerging within the first 2 years after drug initiation. This novel tenofovir-cLEE signal should be further investigated....

  2. Effect of granulocyte colony-stimulating factor (G-CSF) in human immunodeficiency virus-infected patients: increase in numbers of naive CD4 cells and CD34 cells makes G-CSF a candidate for use in gene therapy or to support antiretroviral therapy

    DEFF Research Database (Denmark)

    Nielsen, S D; Afzelius, P; Dam-Larsen, S;

    1998-01-01

    The potential of granulocyte colony-stimulating factor (G-CSF) to mobilize CD4 cells and/or CD34 cells for use in gene therapy or to support antiretroviral therapy was examined. Ten human immunodeficiency virus-infected patients were treated with G-CSF (300 microg/day) for 5 days. Numbers of CD4....... Furthermore, the fraction of naive CD4 cells increased. These findings have implications for the design of immunotherapy or gene therapy protocols....... and CD34 cells were measured. To examine the numbers of naive and memory type CD4 cells, CD4 cell coexpression of CD45RA and CD45RO was measured. Functionality of mobilized CD4 cells was examined by use of the proliferation assay and interleukin-2 ELISA. The number of CD34 cells increased from 1.50 to 20...

  3. Decrease in immune activation in HIV-infected patients treated with highly active antiretroviral therapy correlates with the function of hematopoietic progenitor cells and the number of naive CD4+ cells

    DEFF Research Database (Denmark)

    Nielsen, S D; Sørensen, T U; Ersbøll, A K;

    2000-01-01

    determined. During the study period, the naive CD4+ count and the cloning efficiency increased significantly. Immune activation was found in HIV-infected patients and decreased during HAART. The level of immune activation correlated negatively with both the naive CD4+ count and the function of progenitor...... cells. A negative correlation was found between apoptosis and the naive CD4+ count. Alterations in cytokine production during HAART or correlation between cytokine production and the naive CD4+ count or the cloning efficiency of progenitor cells were not detected. In conclusion, immune activation in HIV...

  4. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Weber, Rainer; Reiss, Peter;

    2003-01-01

    OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...... to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs......, a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral...

  5. Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons

    DEFF Research Database (Denmark)

    Ryom, Lene; Lundgren, Jens Dilling; De Wit, Stéphane

    2016-01-01

    cohort study. METHODS: Data collection on adverse events of anti-HIV drugs study (D:A:D) participants were followed until the first of ESLD (variceal bleeding, hepatic encephalopathy, hepatorenal syndrome or liver transplantation), HCC (histology or α-fetoprotein along with imaging), death, 6 months...... after last visit or 1 February 2014. Associations between ESLD/HCC and cumulative use of individual antiretrovirals were investigated using Poisson regression adjusting for potential confounders. RESULTS: During a median follow-up of 8.4 years, 319 ESLD/HCC cases occurred [incidence 1.01/1000 person...

  6. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Weber, Rainer; Reiss, Peter;

    2003-01-01

    to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs...... of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated total cholesterol level. CONCLUSION: HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially......OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...

  7. Antiretroviral drug-related liver mortality among HIV-positive persons in the absence of hepatitis B or C virus coinfection

    DEFF Research Database (Denmark)

    Kovari, Helen; Sabin, Caroline A; Ledergerber, Bruno;

    2013-01-01

    Liver diseases are the leading causes of death in human immunodeficiency virus (HIV)-positive persons since the widespread use of combination antiretroviral treatment (cART). Most of these deaths are due to hepatitis C (HCV) or B (HBV) virus coinfections. Little is known about other causes...

  8. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function : the D:A:D study

    NARCIS (Netherlands)

    Ryom, Lene; Mocroft, Amanda; Kirk, Ole; Worm, Signe W; Kamara, David A; Reiss, Peter; Ross, Michael; Fux, Christoph A; Morlat, Philippe; Moranne, Olivier; Smith, Colette; Lundgren, Jens D; Schölvinck, Elisabeth H.

    2013-01-01

    BACKGROUND: Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown. METHODS: D:A:D study participants with an estimated glomerul

  9. Predictors of adherence to antiretroviral therapy among HIV-infected persons: a prospective study in Southwest Ethiopia

    Directory of Open Access Journals (Sweden)

    Girma Belaineh

    2008-07-01

    Full Text Available Abstract Background The devastating impact of AIDS in the world especially in sub-Saharan Africa has led to an unprecedented global effort to ensure access to antiretroviral (ARV drugs. Given that medication-taking behavior can immensely affect an individual's response; ART adherence is now widely recognized as an 'Achilles heel' for the successful outcome. The present study was undertaken to investigate the rate and predictors of adherence to antiretroviral therapy among HIV-infected persons in southwest Ethiopia. Methods The study was conducted in the antiretroviral therapy unit of Jimma University Specialized Hospital. A prospective study was undertaken on a total of 400 HIV infected person. Data were collected using a pre-tested interviewer-administered structured questionnaire at first month (M0 and third month (M3 follow up visits. Results A total of 400 and 383 patients at baseline (M0 and at follow up visit (M3 respectively were interviewed. Self-reported dose adherence in the study area was 94.3%. The rate considering the combined indicator (dose, time and food was 75.7%. Within a three month follow up period, dose adherence decreased by 2% and overall adherence rate decreased by more than 3%. Adherence was common in those patients who have a social support (OR, 1.82, 95%CI, 1.04, 3.21. Patients who were not depressed were two times more likely to be adherent than those who were depressed (OR, 2.13, 95%CI, 1.18, 3.81. However, at the follow up visit, social support (OR, 2.42, 95%CI, 1.29, 4.55 and the use of memory aids (OR, 3.29, 95%CI, 1.44, 7.51 were found to be independent predictors of adherence. The principal reasons reported for skipping doses in this study were simply forgetting, feeling sick or ill, being busy and running out of medication in more than 75% of the cases. Conclusion The self reported adherence rate was high in the study area. The study showed that adherence is a dynamic process which changes overtime and cannot

  10. Micronutrient deficiency and treatment adherence in a randomized controlled trial of micronutrient supplementation in ART-naive persons with HIV.

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    Louise Balfour

    Full Text Available INTRODUCTION: The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection. OBJECTIVE: We planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions. METHODS: Participants receive eight capsules twice daily of 1 high-dose or 2 RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS and short-term recall HIV Adherence Treatment Scale (HATS. RESULTS: Prior micronutrient supplementation (within 30 days was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%80% in 75% of participants. CONCLUSION: Micronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00798772.

  11. Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study

    DEFF Research Database (Denmark)

    Lodwick, Rebecca K; Sabin, Caroline A; Porter, Kholoud;

    2010-01-01

    Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries....

  12. Associations between 25-hydroxyvitamin D and immunologic, metabolic, inflammatory markers in treatment-naive HIV-infected persons: the ANRS CO9 «COPANA» cohort study.

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    Camille Legeai

    Full Text Available OBJECTIVES: Low 25(OHD has been associated with dyslipidemia, insulin resistance and inflammation in both general and HIV-infected (mostly treated populations. We investigated these associations in antiretroviral-naïve HIV-infected persons. DESIGN: We measured plasma 25(OHD, metabolic, immunologic and inflammatory markers in 355 persons (204 Whites, 151 Blacks at enrollment in the ANRS COPANA cohort. METHODS: 25(OHD levels were categorized <10 ng/mL (severe deficiency and <20 ng/mL (deficiency. Statistical analyses were adjusted for sampling season, ethnicity and the interaction between season and ethnicity. RESULTS: 25(OHD insufficiency (<30 ng/mL, deficiency (<20 ng/mL and severe deficiency (<10 ng/mL were highly prevalent (93%, 67% and 24% of patients, respectively. Blacks had significantly lower 25(OHD than Whites (median: 13 vs. 17 ng/mL, P<0.001, with markedly less pronounced seasonal variation. Smoking and drinking alcohol were associated with having a 25 OHD level<10 ng/mL. In patients with 25(OHD<10 ng/mL, the proportion of persons with a CD4 count<100/mm(3 was higher than in patients with 25(OHD≥10 ng/mL (18.8% vs. 10.7%, P = 0.04. Persons with 25 OHD<10 ng/mL had higher levels of hsCRP (1.60 mg/L [IQR: 0.59-5.76] vs. 1.27 mg/L [0.58-3,39], P = 0.03 and resistin (16.81 ng/L [IQR: 13.82-25.74] vs. 11.56 ng/L [IQR: 8.87-20.46], P = 0.02, and, among Blacks only, sTNFR2 (2.92 ng/mL [2.31-4.13] vs. 2.67 ng/mL, [1.90-3.23], P = 0.04. The strength and significance of the association between CD4<100/mm(3 and 25 OHD<10 ng/mL were reduced after adjustment on sTNFR1, sTNFR2, and hsCRP levels. In multivariate analysis, a CD4 count <100/mm(3, resistin concentration and smoking were independently associated with 25(OHD<10 ng/mL. CONCLUSIONS: Severe vitamin D deficiency was associated with low CD4 counts and increased markers of inflammation in ARV-naïve HIV-infected persons.

  13. In vivo mitochondrial function in HIV-infected persons treated with contemporary anti-retroviral therapy: a magnetic resonance spectroscopy study.

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    Brendan A I Payne

    Full Text Available Modern anti-retroviral therapy is highly effective at suppressing viral replication and restoring immune function in HIV-infected persons. However, such individuals show reduced physiological performance and increased frailty compared with age-matched uninfected persons. Contemporary anti-retroviral therapy is thought to be largely free from neuromuscular complications, whereas several anti-retroviral drugs previously in common usage have been associated with mitochondrial toxicity. It has recently been established that patients with prior exposure to such drugs exhibit irreversible cellular and molecular mitochondrial defects. However the functional significance of such damage remains unknown. Here we use phosphorus magnetic resonance spectroscopy ((31P-MRS to measure in vivo muscle mitochondrial oxidative function, in patients treated with contemporary anti-retroviral therapy, and compare with biopsy findings (cytochrome c oxidase (COX histochemistry. We show that dynamic oxidative function (post-exertional ATP (adenosine triphosphate resynthesis was largely maintained in the face of mild to moderate COX defects (affecting up to ∼10% of fibers: τ½ ADP (half-life of adenosine diphosphate clearance, HIV-infected 22.1±9.9 s, HIV-uninfected 18.8±4.4 s, p = 0.09. In contrast, HIV-infected patients had a significant derangement of resting state ATP metabolism compared with controls: ADP/ATP ratio, HIV-infected 1.24±0.08×10(-3, HIV-uninfected 1.16±0.05×10(-3, p = 0.001. These observations are broadly reassuring in that they suggest that in vivo mitochondrial function in patients on contemporary anti-retroviral therapy is largely maintained at the whole organ level, despite histochemical (COX defects within individual cells. Basal energy requirements may nevertheless be increased.

  14. Immunological profile in persons under antiretroviral therapy in a rural Nigerian hospital

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    Baba Maiyaki Musa

    2010-09-01

    Full Text Available Human immunodeficiency virus (HIV contributes significantly to morbidity and mortality in sub-Saharan Africa, with Nigeria having the third highest burden of HIV infection globally; efforts are made to increases access to HIV/AIDS care and treatment. This has currently reached rural areas with limited manpower and laboratory evaluation capacity. This review is necessitated by the paucity of interim report on treatment profile in Nigerian rural areas. We report on the immunological profile of patients on antiretroviral therapy (ART in Otukpo General Hospital, a rural Nigerian hospital. This is a retrospective cohort study of patients receiving ART treatment and care, on April 2009, when 2347 patients were under ART therapy. Out of these, 96 patients were selected by simple random sampling from hospital register, with their data abstracted from standardized Ministry of Health registers and facility documents kept at the hospital, and analyzed for descriptive and biometric measures. Ninty-six patients (29% males with a median age of 35 years, median baseline CD4 lymphocyte count 221 cells/mL, median one year CD4 lymphocyte count of 356 cells/mL and median one year CD4 lymphocyte increment of 124 cells/mL were studied. There is no statistically significant difference in baseline CD4 lymphocyte count when data is disaggregated by type of drug regimen (AZT, D4T and TDF. Fourty-four percent, 23% and 33% of patients were on TDF, D4T & AZT based regimen, respectively (P=0.66. Increment of >100 cells/mL was seen in 64.58% of the reviewed patients. There was a higher CD4 lymphocyte count increment in patients on TDF & D4T compared with those in AZT based regimens (ANOVA; P<0.0003. Multivariate linear regression model showed one year CD4 lymphocyte count, one year increment in CD4 lymphocyte count, WBC count, and absolute neutrophil count to be significant correlates of baseline CD4 lymphocyte count (P<0.0001. Equally, multivariate logistic regression found

  15. Brief Report: Dolutegravir Plus Abacavir/Lamivudine for the Treatment of HIV-1 Infection in Antiretroviral Therapy-Naive Patients: Week 96 and Week 144 Results From the SINGLE Randomized Clinical Trial.

    Science.gov (United States)

    Walmsley, Sharon; Baumgarten, Axel; Berenguer, Juan; Felizarta, Franco; Florence, Eric; Khuong-Josses, Marie-Aude; Kilby, J Michael; Lutz, Thomas; Podzamczer, Daniel; Portilla, Joaquin; Roth, Norman; Wong, Deborah; Granier, Catherine; Wynne, Brian; Pappa, Keith

    2015-12-15

    The SINGLE study was a randomized, double-blind, noninferiority study that evaluated the safety and efficacy of 50 mg dolutegravir + abacavir/lamivudine versus efavirenz/tenofovir/emtricitabine in 833 ART-naive HIV-1 + participants. Of 833 randomized participants, 71% in the dolutegravir + abacavir/lamivudine arm and 63% in the efavirenz/tenofovir/emtricitabine arm maintained viral loads of abacavir/lamivudine arm [dolutegravir + abacavir/lamivudine arm, 16 (4%); efavirenz/tenofovir/emtricitabine arm, 58 (14%)] through W144 [corrected]. No treatment-emergent integrase or nucleoside resistance was observed in dolutegravir + abacavir/lamivudine recipients through W144.

  16. Socioeconomic status and survival of persons with AIDS before and after the introduction of highly active antiretroviral therapy. Lazio AIDS Surveillance Collaborative Group.

    Science.gov (United States)

    Rapiti, E; Porta, D; Forastiere, F; Fusco, D; Perucci, C A

    2000-09-01

    We estimated the AIDS survival by neighborhood socioeconomic status before (1993-1995) and after (1996-1997) the introduction of highly active antiretroviral therapy in Rome, Italy, in a retrospective cohort of persons with AIDS followed through July 31, 1998. Participants included 1,474 persons with AIDS residing in Rome who were diagnosed in 1993-1997. We calculated hazard ratios (HRs) of death for two diagnostic periods (before and after highly active antiretroviral therapy was introduced) by neighborhood socioeconomic status categorized into four levels (level I = highest socioeconomic status), using the Cox model and adjusting for gender, age, intravenous drug use, CD4 cell count at diagnosis, AIDS-defining disease, and hospital of diagnosis. Thirty-four per cent of persons with AIDS (N = 503) had survived as of mid-1998. For persons with AIDS diagnosed in 1993-1995, we found little difference in the risk of death by neighborhood socioeconomic status. For 1996-1997, the risk of death was greater for persons with lower neighborhood socioeconomic status, especially for levels III and IV [HR = 2.81 (95% confidence interval = 1.38-5.76), and HR = 2.55 (95% confidence interval = 1.27-5.14), respectively, compared with level I]. Stratified analyses showed that the greatest difference was found for women and drug users. In conclusion, even in a country with universal health coverage that provides therapy at no cost, differences in survival of persons with AIDS have emerged by neighborhood socioeconomic status since highly active antiretroviral therapy was introduced. Inequalities in health-care access or in medical management, or poor adherence to treatment, could explain the observed heterogeneity.

  17. The Naive Central Banker

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    Marcelo de Carvalho Griebeler

    2015-09-01

    Full Text Available There has been in some countries a trend of assigning other functions to central banks besides price stability. The most suggested function to be added to monetary authority’s obligations is to pursue economic growth or full employment. In this paper we characterize the behavior and analyse the optimal monetary policy of, what we call, a naive central banker. We describe the naive behavior as one that does face the inflation-unemployment trade-off, but it tries to minimize both variables simultaneously. Our findings, both under discretion and commitment, indicate that the naive central banker delivers lower expected inflation and inflation variance than the benchmark behavior whenever the economy is rigid enough. However, the degree of conservativeness also affects this result, such that the less conservative the naive policymaker, the more rigidity is necessary.

  18. Trends in early initiation of antiretroviral therapy and characteristics of persons with HIV initiating therapy in San Francisco, 2007-2011.

    Science.gov (United States)

    Hsu, Ling Chin; Truong, Hong-Ha M; Vittinghoff, Eric; Zhi, Qi; Scheer, Susan; Schwarcz, Sandra

    2014-05-01

    In 2010, the San Francisco Department of Public Health offered antiretroviral therapy (ART) to all its patients with human immunodeficiency virus (HIV) regardless of CD4 count. We assessed trends in time from diagnosis to ART initiation and factors associated with ART initiation among San Francisco residents living with HIV between 2007 and 2011. Time to ART initiation decreased among those diagnosed with higher CD4 count. ART initiation rate was significantly higher in recent years and lower among African Americans, men who have sex with men who also inject drugs, and persons aged ≥50 years. We found a trend toward early treatment. However, racial and social disparities persist.

  19. Adherence to antiretroviral therapy and its determinants among persons living with HIV/AIDS in Bayelsa state, Nigeria

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    Suleiman IA

    2016-04-01

    Full Text Available Background: A high level of adherence is required to achieve the desired outcomes of antiretroviral therapy. There is paucity of information about adherence to combined antiretroviral therapy in Bayelsa State of southern Nigeria. Objectives: The objectives of the study were to determine the level of adherence to combined antiretroviral therapy among the patients, evaluate the improvement in their immune status and identify reasons for sub-optimal adherence to therapy. Methods: The cross-sectional study involved administration of an adapted and pretested questionnaire to 601 consented patients attending the two tertiary health institutions in Bayesla State, Nigeria: The Federal Medical Centre, Yenagoa and the Niger-Delta University Teaching Hospital Okolobiri. The tool was divided into various sections such as socio-demographic data, HIV knowledge and adherence to combined antiretroviral therapy. Information on the patient's CD4+ T cells count was retrieved from their medical records. Adherence was assessed by asking patients to recall their intake of prescribed doses in the last fourteen days and subjects who had 95-100% of the prescribed antiretroviral drugs were considered adherent. Results: Three hundred and forty eight (57.9% of the subjects were females and 253 (42.1% were males. The majority of them, 557 (92.7% have good knowledge of HIV and combined anti-retroviral therapy with a score of 70.0% and above. A larger proportion of the respondents, 441 (73.4%, had ≥95% adherence. Some of the most important reasons giving for missing doses include, “simply forgot” 147 (24.5%, and “wanted to avoid the side-effects of drugs” 33(5.5%. There were remarkable improvements in the immune status of the subjects with an increment in the proportion of the subjects with CD4+ T cells count of greater than 350 cells/mm3 from 33 (5.5% at therapy initiation to 338 (56.3% at study period (p<0.0001. Conclusion: The adherence level of 73.4% was low

  20. A Comparison of the Diabetes Risk Score in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART and HAART-Naive Patients at the Limbe Regional Hospital, Cameroon.

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    Christian Akem Dimala

    Full Text Available Highly active antiretroviral therapy (HAART has been associated with dysglycaemia. However, there is scarce data on the risk of developing diabetes mellitus (DM in HIV/AIDS patients in Africa.Primarily to quantify and compare the risk of having diabetes mellitus in HIV/AIDS patients on HAART and HAART-naïve patients in Limbe, Cameroon; and secondarily to determine if there is an association between HAART and increased DM risk.A cross-sectional study was conducted at the Limbe Regional Hospital HIV treatment center between April and June 2013, involving 200 HIV/AIDS patients (100 on first-line HAART regimens for at least 12 months matched by age and gender to 100 HAART-naïve patients. The Diabetes Risk Score (DRS was calculated using a clinically validated model based on routinely recorded primary care parameters. A DRS ≥ 7% was considered as indicative of an increased risk of developing DM.The median DRS was significantly higher in patients on HAART (2.30% than in HAART-naïve patients (1.62%, p = 0.002. The prevalence of the increased DM risk (DRS ≥ 7% was significantly higher in patients on HAART, 31% (95% CI: 22.13-41.03 than in HAART-naïve patients, 17% (95% CI: 10.23-25.82, p = 0.020. HAART was significantly associated with an increased DM risk, the odds ratio of the HAART group compared to the HAART-naïve group was 2.19 (95% CI: 1.12-4.30, p = 0.020. However, no association was found after adjusting for BMI-defined overweight, hypertension, age, sex, family history of DM and smoking (Odds ratio = 1.22, 95% CI: 0.42-3.59, p = 0.708. Higher BMI and hypertension accounted for the increased risk of DM in patients on HAART. Also, more than 82% of the participants were receiving or had ever used Zidovudine based HAART regimens.HIV/AIDS patients on HAART could be at a greater risk of having DM than HAART-naïve patients as a result of the effect of HAART on risk factors of DM such as BMI and blood pressure.

  1. The RADAR study: week 48 safety and efficacy of RAltegravir combined with boosted DARunavir compared to tenofovir/emtricitabine combined with boosted darunavir in antiretroviral-naive patients. Impact on bone health.

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    Roger J Bedimo

    Full Text Available NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression.In the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL (n = 42 or tenofovir/emtricitabine (TDF/FTC (n = 43, each with ritonavir-boosted darunavir (DRV/r. Virologic efficacy was assessed at weeks 24 and 48. Bone mineral density (BMD was assessed by dual energy X-ray absorptiometry (DXA scan at baseline and week 48, and bone turnover markers (BTM assessed at weeks 0, 16 and 48.Using an intention-to-treat analysis, 62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL<48 copies/mL at week 48 (p = 0.045; chi-square test. The proportions of patients achieving VL<200 copies/mL were similar: 72.5% and 86.0% (p = 0.175. Premature treatment discontinuation was the main cause for failure. No treatment-emergent resistance was observed. Changes from baseline in RAL vs. TDF/FTC for CD4+ (+199 vs. +216 cells/µL, p = 0.63, total cholesterol/HDL (-0.25 vs. -0.71 mg/dL (p = 0.270, and eGFR (-4.4 vs. -7.9 ml/min, p = 0.44 were comparable between groups. Changes in subtotal BMD to week 48 were: +9.2 with RAL vs. -7 g/cm2 with TDF/FTC (p = 0.002. Mean CTX changes were +0.04 vs. +0.24 ng/mL (p = 0.001, and mean P1NP changes were +3.59 vs. +30.09 ng/mL (p = 0.023. BTM changes at week 16 predicted change in BMD by week 48 (R = -0.394, p = 0.003 for CTX; and R = -0.477, p<0.001 for P1NP.The NRTI-sparing regimen RAL+DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC+DRV/r, but was better with regard to markers of bone health.ClinicalTrials.gov NCT 00677300.

  2. Pessoas vivendo com HIV/AIDS: variáveis associadas à adesão ao tratamento anti-retroviral Persons living with HIV/AIDS: factors associated with adherence to antiretroviral treatment

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    Eliane Maria Fleury Seidl

    2007-10-01

    Full Text Available O estudo objetivou descrever o comportamento de adesão ao tratamento anti-retroviral em pessoas vivendo com HIV/AIDS e investigar preditores da adesão entre as variáveis escolaridade, presença de efeitos colaterais, interrupção anterior da terapia anti-retroviral (TARV por conta própria, auto-estima, expectativa de auto-eficácia, estratégias de enfrentamento, suporte social e satisfação com a relação profissional de saúde-usuário. Adesão foi medida pelo auto-relato da perda do número de comprimidos/cápsulas dos medicamentos anti-retrovirais na última semana e mês, sendo considerada satisfatória na ocorrência de omissão inferior a 5% do total prescrito. Participaram 101 pessoas, 60,4% homens, idades entre 20 a 71 anos (M = 37,9 anos, 73,3% sintomáticos. A coleta de dados incluiu entrevista e instrumentos auto-aplicáveis. A maioria (n = 73; 72,3% relatou adesão igual ou superior a 95%. Nos resultados da regressão logística, interrupção anterior da TARV e expectativa de auto-eficácia foram preditores significativos da adesão. Faz-se necessária a qualificação da assistência pela constituição de equipes interdisciplinares, para o desenvolvimento de abordagens adequadas às dificuldades médicas e psicossociais de adesão das pessoas vivendo com HIV/AIDS.This study aimed to describe the adherence of persons living with HIV/AIDS to antiretroviral therapy (ART and to investigate adherence predictors among the following: level of schooling, presence of side effects, current or previous interruption of ART by the persons themselves, self-esteem, self-efficacy expectation, coping strategies, social support, and satisfaction with the health professional-patient relationship. Adherence was measured by self-reported number of ART pills/capsules missed during the previous week and previous month, evaluated as satisfactory when less than 5%. 101 HIV+ adults took part in this study, 60.4% males, ranging from 20 to 71 years

  3. Antiretroviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  4. Naive Realism about Operators

    OpenAIRE

    Daumer, Martin; Dürr, Detlef; Goldstein, Sheldon; Zanghì, Nino

    1996-01-01

    A source of much difficulty and confusion in the interpretation of quantum mechanics is a ``naive realism about operators.'' By this we refer to various ways of taking too seriously the notion of operator-as-observable, and in particular to the all too casual talk about ``measuring operators'' that occurs when the subject is quantum mechanics. Without a specification of what should be meant by ``measuring'' a quantum observable, such an expression can have no clear meaning. A definite specifi...

  5. Outcomes of Second Combination Antiretroviral Therapy Regimens Among HIV-Infected Persons in Clinical Care: A Multicenter Cohort Study

    OpenAIRE

    2013-01-01

    Data on the effectiveness of second-line combination antiretroviral therapy (cART) are limited. We evaluated virologic outcomes of second cART in a multicenter cohort collaboration. The study population initiated first and second modern cART between 1996 and 2010. The second cART required a switch in at least the anchor agent of first cART. We evaluated time to virologic failure of second cART and factors associated with greater risk of failure using multivariable Cox proportional hazards mod...

  6. Transmitted antiretroviral drug resistance in treatment naïve HIV-infected persons in London in 2011 to 2013

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    Katie McFaul

    2014-11-01

    Full Text Available Introduction: Previously published UK data on HIV transmitted drug resistance (TDR shows that it ranges between 3 and 9.4% [1,2]. However, there are no recent data from populations where HIV transmission rates are increasing. The aim of this study was to assess the prevalence of TDR in untreated HIV-infected individuals attending three HIV specialist clinics under the HIV Directorate, Chelsea and Westminster Hospital and based throughout London – the Kobler Clinic, 56 Dean Street and West London Centre for Sexual Health. Methods: We included all patients with a HIV diagnosis, no history of antiretroviral therapy (ART intake, attending one of the three clinics (Kobler (K, 56 Dean Street (DS and West London (WL, between 2011 and 2013 who started antiretrovirals. Reverse transcriptase (RT and protease region sequencing was performed using Vircotype virtual phenotype resistance analysis. Drug resistance mutations were identified according to Stanford University HIV Drug Resistance Database (http://hivdb.stanford.edu/. Results: Among 1705 HIV-1-infected patients enrolled in the study, 1252 were males (919 were MSM, 107 were females and 346 had no gender recorded. Ethnicity was 51.1% white British/Irish/other, 6.1% African, 2.1% Caribbean, 2.8% Asian, 1.3% Indian/Pakistani/Bangladeshi, 4.2%, other, 3.2% not stated, and 29.2% unknown. 547 were from K (84.3% males, 48.3% MSM, 826 were from DS (84.3% males, 71.9% MSM, and 109 from WL (87.2% males, 56.0% MSM, 223 from other sites not specified. 77.5% (1321 of 1705 of patients had baseline viral resistance testing performed. Prevalence of primary resistance in those with a baseline viral resistance test was 13.5% overall: 19.3% in K, 14.9% in DS, and 14.7% in WL. The most common mutations detected were: NRTI: 184V, 215F, 41L; NNRTI 103N, 179D, 90I; PI 90M, 46I, and 82A. Among patients who tested with TDR, 79.1% had one single mutation, 18.7% and 2.2% exhibited dual or triple class-resistant viruses

  7. Naive realism about operators

    CERN Document Server

    Daumer, M; Goldstein, S; Zanghì, N; Daumer, Martin; Durr, Detlef; Goldstein, Sheldon; Zangh, Nino

    1996-01-01

    A source of much difficulty and confusion in the interpretation of quantum mechanics is a ``naive realism about operators.'' By this we refer to various ways of taking too seriously the notion of operator-as-observable, and in particular to the all too casual talk about ``measuring operators'' that occurs when the subject is quantum mechanics. Without a specification of what should be meant by ``measuring'' a quantum observable, such an expression can have no clear meaning. A definite specification is provided by Bohmian mechanics, a theory that emerges from Sch\\"rodinger's equation for a system of particles when we merely insist that ``particles'' means particles. Bohmian mechanics clarifies the status and the role of operators as observables in quantum mechanics by providing the operational details absent from standard quantum mechanics. It thereby allows us to readily dismiss all the radical claims traditionally enveloping the transition from the classical to the quantum realm---for example, that we must a...

  8. Occurrence of intestinal parasites amongst persons on highly active antiretroviral drug therapy in Calabar, Cross River State, Nigeria

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    Paul C. Inyang-Etoh

    2015-02-01

    Full Text Available Opportunistic and intestinal parasite infections are common health problem among HIV/AIDS patients. Early detection and treatment of these parasites are important to improve the quality of life of this category of patients. The occurrence of intestinal parasites among 400 patients on highly active anti-retroviral drug therapy (HAART aged 11-60 years was investigated. Standard parasitological techniques like direct microscopy, formol ether concentration and modified Ziehl- Neelsen staining techniques were used to analyze the stool samples. Intestinal parasite infections were positive in 116 (29% of the subjects on HAART while control subjects had 12 (12% and the difference was statistically significant (P<0.05. Subjects in the age group 21-30 years had the highest infection rate 54 (35.1%. There was no statistically significant difference in infection according to age (P>0.05. Females 76 (32.5% had a higher prevalence rate than males 40 (24.1%. But there was no statistically significant difference in infection according to gender (P<0.05. Patients with CD4 count of less than 200 cells/mm3 were observed to be more infected than those with CD4 count of more than 200 cells/mm3. There was a strong positive correlation (r=0.94 between CD4 count and the occurrence of intestinal parasite infection. Protozoan parasites 84 (21.0% accounted for a higher prevalence rate than helminthic parasites 32 (8.0%. These findings has revealed a high prevalence of intestinal parasite infection among patients on HAART thus the routine screening of stool samples from these category of patients for intestinal parasites is advocated for effective management of the disease.

  9. YAP Induces Human Naive Pluripotency

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    Han Qin

    2016-03-01

    Full Text Available The human naive pluripotent stem cell (PSC state, corresponding to a pre-implantation stage of development, has been difficult to capture and sustain in vitro. We report that the Hippo pathway effector YAP is nuclearly localized in the inner cell mass of human blastocysts. Overexpression of YAP in human embryonic stem cells (ESCs and induced PSCs (iPSCs promotes the generation of naive PSCs. Lysophosphatidic acid (LPA can partially substitute for YAP to generate transgene-free human naive PSCs. YAP- or LPA-induced naive PSCs have a rapid clonal growth rate, a normal karyotype, the ability to form teratomas, transcriptional similarities to human pre-implantation embryos, reduced heterochromatin levels, and other hallmarks of the naive state. YAP/LPA act in part by suppressing differentiation-inducing effects of GSK3 inhibition. CRISPR/Cas9-generated YAP−/− cells have an impaired ability to form colonies in naive but not primed conditions. These results uncover an unexpected role for YAP in the human naive state, with implications for early human embryology.

  10. Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya

    Science.gov (United States)

    Maman, David; Auma, Erick; Were, Kennedy; Fredrick, Harrison; Owiti, Prestone; Opollo, Valarie; Etard, Jean-François; Mukui, Irene; Kim, Andrea A.; Zeh, Clement

    2017-01-01

    HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15–59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7–17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8–11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2–14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2–6.2) for protease inhibitors. Three (3.4% 95% CI 0.8–10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population

  11. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function

    DEFF Research Database (Denmark)

    Nielsen, Lene Ryom; Mocroft, A.; Kirk, O.

    2013-01-01

    glomerular filtration rate (eGFR) of ≥90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of ≤70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or ≤60 mL/min (a value indicative of moderately severe chronic kidney disease [CKD......GFR of ≤70 mL/min (incidence rate, 4.78 cases/1000 person-years of follow-up [95% confidence interval "CI", 4.35-5.22]) and 131 (0.6%) experienced CKD (incidence rate, 1.33 cases/1000 person-years of follow-up [95% CI, 1.10-1.56]) during a median follow-up duration of 4.5 years (interquartile range [IQR], 2.......7-6.1 years). A current eGFR of 60-70 mL/min caused significantly higher rates of discontinuation of tenofovir (adjusted incidence rate ratio [aIRR], 1.72 [95% CI, 1.38-2.14]) but not other ARVs compared with a current eGFR of ≥90 mL/min. Cumulative tenofovir use (aIRR, 1.18/year [95% CI, 1...

  12. Individualization of antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Pavlos R

    2011-12-01

    Full Text Available Rebecca Pavlos, Elizabeth J PhillipsInstitute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, AustraliaAbstract: Antiretroviral therapy (ART has evolved considerably over the last three decades. From the early days of monotherapy with high toxicities and pill burdens, through to larger pill burdens and more potent combination therapies, and finally, from 2005 and beyond where we now have the choice of low pill burdens and once-daily therapies. More convenient and less toxic regimens are also becoming available, even in resource-poor settings. An understanding of the individual variation in response to ART, both efficacy and toxicity, has evolved over this time. The strong association of the major histocompatibility class I allele HLA-B*5701 and abacavir hypersensitivity, and its translation and use in routine HIV clinical practice as a predictive marker with 100% negative predictive value, has been a success story and a notable example of the challenges and triumphs in bringing pharmacogenetics to the clinic. In real clinical practice, however, it is going to be the exception rather than the rule that individual biomarkers will definitively guide patient therapy. The need for individualized approaches to ART has been further increased by the importance of non-AIDS comorbidities in HIV clinical practice. In the future, the ideal utilization of the individualized approach to ART will likely consist of a combined approach using a combination of knowledge of drug, virus, and host (pharmacogenetic and pharmacoecologic [factors in the individual's environment that may be dynamic over time] information to guide the truly personalized prescription. This review will focus on our knowledge of the pharmacogenetics of the efficacy and toxicity of currently available antiretroviral agents and the current and potential utility of such information and approaches in present and future HIV clinical care.Keywords: HIV

  13. When to start antiretroviral therapy

    DEFF Research Database (Denmark)

    Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred M

    2013-01-01

    , it remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/μl. The question of when the best time is to initiate ART during early HIV infection has......Strategies for use of antiretroviral therapy (ART) have traditionally focused on providing treatment to persons who stand to benefit immediately from initiating the therapy. There is global consensus that any HIV+ person with CD4 counts less than 350 cells/μl should initiate ART. However...

  14. Naive Bayesian for Email Filtering

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The paper presents a method of email filter based on Naive Bayesian theory that can effectively filter junk mail and illegal mail. Furthermore, the keys of implementation are discussed in detail. The filtering model is obtained from training set of email. The filtering can be done without the users specification of filtering rules.

  15. Study of HIV-1 Drug Resistance in Patients Receiving Free Antiretroviral Therapy in China

    Institute of Scientific and Technical Information of China (English)

    Xin-ping LI; Hai-wei ZHOU; Jiang-hong HUANG; Hong PENG; Peng-fei MA; Yi-ming SHAO; Hui XING; Zhe WANG; Xue-feng SI; Lian-en WANG; Hua CHENG; Wei-guo CUI; Shu-lin JIANG; Ling-jie LIAO

    2007-01-01

    To investigate the prevalence of drug-resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan, China, a total of 431 plasma samples were collected in Queshan county between 2003 and 2004, from patients undergoing the antiretroviral regimen Zidovudine + Didanosine + Nevirapine (Azt+Ddi+Nvp). Personal information was collected by face to face interview. Viral load and genotypic drug resistance were tested. Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program (http://hivdb.stanford.edu). Overall, 38.5% of treatment-naive patients had undetectable plasma viral load (VL), the rate significantly increased to 61.9% in 0 to 6 months treatment patients (mean 3 months) (P<0.005) but again significantly decrease to 38.6% in 6 to 12 months treatment patients (mean 9 months) (P<0.001) and 40.0% in patients receiving more than 12 months treatment (mean 16 months) (P<0.005). The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%, 48.6%, 70.8%, 72.3% in treatment-na(1)ve, 0 to 6 months treatment, 6 to 12 months treatment, and treatment for greater than 12 months patients, respectively. No mutation associated with resistance to Protease inhibitor (PI) was detected in this study. Nucleoside RT inhibitor (NRTI) mutations always emerged after non-nucleoside RT inhibitor (NNRTI) mutations, and were only found in patients treated for more than 6 months, with a frequency less than 5%, with the exception of mutation T215Y (12.8%, 6/47) which occurred in patients treated for more than 12 months. NNRTI mutations emerged quickly after therapy begun, and increased significantly in patients treated for more than 6 months (P<0.005), and the most frequent mutations were K103N, V106A, Y181C, G190A. There had been optimal viral suppression in

  16. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Carr, Andrew; Neuhaus, Jacquie;

    2008-01-01

    BACKGROUND: The SMART trial found a raised risk of cardiovascular disease (CVD) events in patients undergoing CD4+ T cell-count guided intermittent antiretroviral therapy (ART) compared with patients on continuous ART. Exploratory analyses were performed to better understand the reasons for this ......BACKGROUND: The SMART trial found a raised risk of cardiovascular disease (CVD) events in patients undergoing CD4+ T cell-count guided intermittent antiretroviral therapy (ART) compared with patients on continuous ART. Exploratory analyses were performed to better understand the reasons...... for this observation. METHODS: A total of 5,472 patients with CD4+ T-cell counts >350 cells/mm3 were recruited and randomized to either continuous ART (the viral suppression arm; VS) or CD4+ T-cell count-guided use of ART (the drug conservation arm; DC). RESULTS: Major CVD events developed in 79 patients. The hazard...

  17. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study

    Science.gov (United States)

    Caniglia, Ellen C.; Sabin, Caroline; Robins, James M.; Logan, Roger; Cain, Lauren E.; Abgrall, Sophie; Mugavero, Michael J.; Hernandez-Diaz, Sonia; Meyer, Laurence; Seng, Remonie; Drozd, Daniel R.; Seage, George R.; Bonnet, Fabrice; Dabis, Francois; Moore, Richard R.; Reiss, Peter; van Sighem, Ard; Mathews, William C.; del Amo, Julia; Moreno, Santiago; Deeks, Steven G.; Muga, Roberto; Boswell, Stephen L.; Ferrer, Elena; Eron, Joseph J.; Napravnik, Sonia; Jose, Sophie; Phillips, Andrew; Olson, Ashley; Justice, Amy C.; Tate, Janet P.; Bucher, Heiner C.; Egger, Matthias; Touloumi, Giota; Sterne, Jonathan A.; Costagliola, Dominique; Saag, Michael; Hernán, Miguel A.

    2016-01-01

    Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Methods: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9–12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. Results: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9–12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were −5.3 (−18.6 to 7.9) and −31.7 (−52.0 to −11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question. PMID:26895294

  18. The effect of valacyclovir on HIV and HSV-2 in HIV-infected persons on antiretroviral therapy with previously unrecognised HSV-2.

    Science.gov (United States)

    Van Wagoner, Nicholas; Geisler, William M; Bachmann, Laura H; Hook, Edward W

    2015-07-01

    In the absence of antiretroviral therapy, valacyclovir may reduce HIV viral load and increase CD4+ T-lymphocyte count. We sought to evaluate the impact of valacyclovir on HIV and HSV-2 in co-infected patients receiving antiretroviral therapy with previously unrecognised HSV-2 infection. A prospective, randomised-controlled, 24-week trial of valacyclovir 1000 mg was performed. Mean CD4+ T-lymphocyte count at 24 weeks compared to baseline CD4+ T-lymphocyte count was the primary outcome. HIV viral load suppression, HSV-2 outbreaks and asymptomatic HSV-2 shedding were secondary outcomes. Participants were randomised to valacyclovir (N = 66) or placebo (N = 35). Study completion was 64%. There was no change in 24 weeks compared to baseline CD4+ T-lymphocyte count in either group (valacyclovir p = 0.91, placebo p = 0.59) or the proportion with HIV viral load suppression (valacyclovir p = 0.75, placebo p = 1.0). Genital HSV and asymptomatic HSV-2 shedding were rare. Valacyclovir had no effect on CD4+ T-lymphocyte count or HIV viral load in this population. Valacyclovir may reduce clinical outbreaks and asymptomatic HSV-2 shedding, but the rarity of these events, along with its lack of benefit on HIV, does not support its use in this clinical setting.

  19. Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy

    DEFF Research Database (Denmark)

    Kesselring, Anouk M; Wit, Ferdinand W; Sabin, Caroline A;

    2009-01-01

    BACKGROUND: This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). METHODS: Patients starting NVPc after 1...... to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year...... of starting NVPc and mode of transmission. RESULTS: Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high...

  20. Vitalism in naive biological thinking.

    Science.gov (United States)

    Morris, S C; Taplin, J E; Gelman, S A

    2000-09-01

    Vitalism is the belief that internal bodily organs have agency and that they transmit or exchange a vital force or energy. Three experiments investigated the use of vitalistic explanations for biological phenomena by 5- and 10-year-old English-speaking children and adults, focusing on 2 components: the notion that bodily organs have intentions and the notion that some life force or energy is transmitted. The original Japanese finding of vitalistic thinking was replicated in Experiment 1 with English-speaking 5-year-olds. Experiment 2 indicated that the more active component of vitalism for these children is a belief in the transfer of energy during biological processes, and Experiment 3 suggested an additional, albeit lesser, role for organ intentionality. A belief in vital energy may serve a causal placeholder function within a naive theory of biology until a more precisely formulated mechanism is known.

  1. A simplified combination antiretroviral therapy regimen enhances adherence, treatment satisfaction and quality of life : results of a randomized clinical trial

    NARCIS (Netherlands)

    Langebeek, N.; Sprenger, H. G.; Gisolf, E. H.; Reiss, P.; Sprangers, M. A. G.; Legrand, J. C.; Richter, C.; Nieuwkerk, P. T.

    2014-01-01

    Objectives The aim of the study was to investigate the effect of a simplified regimen, in terms of reducing pill burden, dietary requirements and possible adverse effects, on patients' adherence, treatment satisfaction and quality of life (QoL). Methods Antiretroviral-naive patients who achieved a v

  2. A comparison study of the big five personality characteristics in patients with first-episode, treatment-naive major depressive disorder%首发未用药抑郁症患者大五人格特征对照研究

    Institute of Scientific and Technical Information of China (English)

    沈宗霖; 程宇琪; 刘晓妍; 杨舒然; 叶靖; 许秀峰

    2016-01-01

    Objective To explore the big five personality characteristics of the first-episode, treatment-naive major depressive disorder. Method Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI) was used to assess the personality. A comparison was conducted between 112 first-episode, treatment-naive major depressive disorder (MDD) patients and 99 sex-, age- and education level-matched healthy controls (HC). The Hamilton depression scale (HAMD) was used to evaluate patients’symptom. Result Compared with HC, the neuroticism score in MDD group was significantly higher, while the extraversion, openness, agreeableness and conscientiousness were significantly lower. Lo⁃gistic regression analysis showed that MDD was significantly associated with higher neuroticism (OR=1.106, 95%CI:1.029~1.189, P=0.006) and lower extraversion (OR=0.809, 95%CI: 0.733~0.893, P<0.001) and agreeableness (OR=0.870, 95%CI:0.794~0.953, P=0.003). Linear regression showed that the HAMD score was significantly associated with higher neuroticism (B=0.121, P=0.003). The onset age of MDD was significantly associated with conscientiousness (B=0.015, P=0.001). Conclusion This study confirms that the personality of MDD is different from HC. Higher neuroticism is an important personality facets in treatment-naive patients with first-episode MDD. The low conscientiousness might associate with early age of depression onset.%目的:探讨首发未服药抑郁症患者的大五人格特征。方法采用大五人格量表简化版(neuroticism extraversion openness five-factor inventory, NEO-FFI),对112例首发未服药抑郁症患者及99名性别、年龄、文化背景相匹配的正常对照进行大五人格特征评估,汉密尔顿抑郁量表(Hamilton depression scale,HAMD)评定患者的抑郁症状。结果患者组神经质维度得分高于对照组,而外向性、开放性、宜人性及责任感维度得分均低于对照组(P<0.05)。Logistic回归分析示,抑

  3. Peer support and improved quality of life among persons living with HIV on antiretroviral treatment: A randomised controlled trial from north-eastern Vietnam

    Directory of Open Access Journals (Sweden)

    Van Tam Vu

    2012-05-01

    Full Text Available Abstract Background Among people living with HIV (PLHIV on antiretroviral therapy (ART, it is important to determine how quality of life (QOL may be improved and HIV-related stigma can be lessened over time. This study assessed the effect of peer support on QOL and internal stigma during the first year after initiating ART among a cohort of PLHIV in north-eastern Vietnam. Methods A sub-sample study of a randomised controlled trial was implemented between October 2008 and November 2010 in Quang Ninh, Vietnam. In the intervention group, participants (n = 119 received adherence support from trained peer supporters who visited participants’ houses biweekly during the first two months, thereafter weekly. In the control group, participants (n = 109 were treated according to standard guidelines, including adherence counselling, monthly health check and drug refills. Basic demographics were measured at baseline. QOL and internal stigma were measured using a Vietnamese version of the WHOQOL-HIVBREF and Internal AIDS-related Stigma Scale instruments at baseline and 12 months. T-tests were used to detect the differences between mean values, multilevel linear regressions to determine factors influencing QOL. Results Overall, QOL improved significantly in the intervention group compared to the control group. Among participants initiating ART at clinical stages 3 and 4, education at high school level or above and having experiences of a family member dying from HIV were also associated with higher reported QOL. Among participants at clinical stage 1 and 2, there was no significant effect of peer support, whereas having children was associated with an increased QOL. Viral hepatitis was associated with a decreased QOL in both groups. Lower perceived stigma correlated significantly but weakly with improved QOL, however, there was no significant relation to peer support. Conclusion The peer support intervention improved QOL after 12 months among ART

  4. [The antiretroviral agent Fullevir].

    Science.gov (United States)

    Nosik, D N; Lialina, I K; Kalnina, L B; Lobach, O A; Chataeva, M S; Rasnetsov, L D

    2009-01-01

    The antiretroviral properties of Fullevir (sodium salt of fullerenepolyhydropolyaminocaproic acid) manufactured by IntelFarm Co.) were studied in the human cell culture infected with human immunodeficiency virus (HIV). The agent was ascertained to be able to protect the cell from the cytopathic action of HIV. The 90% effective concentration (EF90) was 5 microg/ml. The 50% average toxic concentration was 400 microg/ml. Testing of different (preventive and therapeutic) Fullevir dosage regimens has shown that the drug is effective when used both an hour before and an hour after infection and when administered simultaneously with cell infection. The longer contact time for the agent with the cells increased the degree of antiviral defense. Co-administration of Fullevir and the HIV reverse transcriptase inhibitor Retrovir (azidothymidine) showed a synergistic antiretroviral effect. Thus, Fullevir may be regarded as a new promising antiretroviral drug for the treatment of HIV infection.

  5. Low Prevalence of Varicella Zoster Virus and Herpes Simplex Virus Type 2 in Saliva from Human Immunodeficiency Virus-Infected Persons in the Era of Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Wang, Chunmei C.; Yepes, Luis C.; Danaher, Robert J.; Berger, Joseph R.; Mootoor, Yunanan; Kryscio, Richard J.; Miller, Craig S.

    2009-01-01

    Objectives Human herpesviruses (HHVs), e.g. herpes simplex virus (HSV) type 1, Epstein-Barr virus and cytomegalovirus, appear in saliva at greater frequency in persons infected with human immunodeficiency virus (HIV) than healthy individuals. However, it is not known if varicella zoster virus (VZV) and HSV-2 appear simultaneously during HIV infection at greater frequency in saliva during this era of highly active antiretroviral therapy (HAART). The aim of this study was to investigate the prevalence and amounts of VZV and HSV-2 in the saliva of HIV-infected, orally asymptomatic patients. Study Design Quantitative polymerase chain reaction was used to investigate the prevalence, quantity, risk, and correlates of salivary VZV and HSV-2 from 59 HIV-seropositive individuals and 53 healthy controls in a case-control, cross-sectional study. Seventy-eight percent of the HIV-seropositive patients (46/59) were taking HAART. Results VZV DNA was detected in the saliva of 5.1% (3/59) of the HIV-positive group and in only one healthy control 1.9% (1/53; P = 0.62). The amount of VZV DNA in the expressors was low, generally less than 1,100 copies/mL with no observed difference between the HIV-positive group and the controls (P= 1.0). HSV-2 DNA was not detected in either group. In the HIV-infected group, VZV shedding occurred in those on HAART, but was not associated with oral lesions, specific CD4+ or CD8+ T-cell levels, or demographic factors. Conclusions VZV was detected at low prevalence in the saliva of HIV-infected persons whereas HSV-2 was not detected in the saliva of this cohort. HAART does not appear to diminish the risk for asymptomatic VZV shedding. PMID:20123407

  6. Metabolic abnormalities and overweight in HIV/AIDS persons-treated with antiretroviral therapy Anormalidades metabólicas e sobrepeso em portadores de HIV/AIDS em terapia com anti-retrovirais

    Directory of Open Access Journals (Sweden)

    Luísa Helena Maia Leite

    2008-06-01

    Full Text Available OBJECTIVE: To describe the proportion of overweight among patients with human immunodeficiency virus/Acquired Immune Deficiency Syndrome and correlate overweight and highly active antiretroviral therapy with metabolic complications. METHODS: A cross-sectional study was conducted among human immunodeficiency virus/Acquired Immune Deficiency Syndrome outpatients undergoing nutritional therapy from 2000 to 2006 in a University Health Center. The sample consisted of 393 human immunodeficiency virus/Acquired Immune Deficiency Syndrome patients. Nutritional and medical records were used as a source of data on personal, clinical and biochemical information. Data analysis included descriptive statistics and the Chi-square test. RESULTS: Sixty-nine percent of the patients were males aging from 26 to 49 years. Overweight and obesity were identified in 49% of this population. The most important metabolic complications were low levels of high-density lipoprotein (70% and high levels of triglycerides (48% and cholesterol (40%. Higher body mass index was associated with higher lipid levels and more evidence of insulin resistance. CONCLUSION: This study demonstrated an important proportion of overweight and obesity among human immunodeficiency virus/Acquired Immune Deficiency Syndrome patients. These results suggest that nutritional interventions and lifestyle modifications may be useful strategies to decrease the cardiovascular risk in this population.OBJETIVO: Estimar a proporção de sobrepeso em pessoas com Vírus da Imunodeficiência Humana /Síndrome da Imunodeficiência Adquirida e avaliar a associação do sobrepeso e do uso da terapia anti-retroviral de alta potência (Highly Active Antiretroviral Therap com a presença de anormalidades metabólicas. MÉTODOS: Foi conduzido um estudo transversal entre pacientes ambulatoriais sob acompanhamento nutricional em um hospital universitário entre 2000-2006. A amostra incluiu 393 pacientes com Vírus da

  7. Mortality and loss to follow-up among HIV-infected persons on long-term antiretroviral therapy in Latin America and the Caribbean

    Science.gov (United States)

    Carriquiry, Gabriela; Fink, Valeria; Koethe, John Robert; Giganti, Mark Joseph; Jayathilake, Karu; Blevins, Meridith; Cahn, Pedro; Grinsztejn, Beatriz; Wolff, Marcelo; Pape, Jean William; Padgett, Denis; Madero, Juan Sierra; Gotuzzo, Eduardo; McGowan, Catherine Carey; Shepherd, Bryan Earl

    2015-01-01

    Introduction Long-term survival of HIV patients after initiating highly active antiretroviral therapy (ART) has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU) and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet). Methods We assessed time from ART initiation (baseline) to death or LTFU between 2000 and 2014 among ART-naïve adults (≥18 years) from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen. Results A total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR): 1.6–6.2). The median age at ART initiation was 36 years (IQR: 30–44), subjects were predominantly male (63%), median CD4 count was 156 cells/µL (IQR: 60–251) and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%). The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI) 17.5–18.8%). A total of 1582 (9.3%) subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR)=1.65 (95% CI 1.47–1.87); p<0.001), lower baseline CD4 (HR=1.95 (95% CI 1.63–2.32) for 50 vs. 350 cells/µL; p<0.001) and

  8. Mortality and loss to follow-up among HIV-infected persons on long-term antiretroviral therapy in Latin America and the Caribbean

    Directory of Open Access Journals (Sweden)

    Gabriela Carriquiry

    2015-07-01

    Full Text Available Introduction: Long-term survival of HIV patients after initiating highly active antiretroviral therapy (ART has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet. Methods: We assessed time from ART initiation (baseline to death or LTFU between 2000 and 2014 among ART-naïve adults (≥18 years from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen. Results: A total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR: 1.6–6.2. The median age at ART initiation was 36 years (IQR: 30–44, subjects were predominantly male (63%, median CD4 count was 156 cells/µL (IQR: 60–251 and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%. The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI 17.5–18.8%. A total of 1582 (9.3% subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR=1.65 (95% CI 1.47–1.87; p<0.001, lower baseline CD4 (HR=1.95 (95% CI 1.63–2.32 for 50 vs. 350 cells/µL; p<0.001 and

  9. Averaged Extended Tree Augmented Naive Classifier

    Directory of Open Access Journals (Sweden)

    Aaron Meehan

    2015-07-01

    Full Text Available This work presents a new general purpose classifier named Averaged Extended Tree Augmented Naive Bayes (AETAN, which is based on combining the advantageous characteristics of Extended Tree Augmented Naive Bayes (ETAN and Averaged One-Dependence Estimator (AODE classifiers. We describe the main properties of the approach and algorithms for learning it, along with an analysis of its computational time complexity. Empirical results with numerous data sets indicate that the new approach is superior to ETAN and AODE in terms of both zero-one classification accuracy and log loss. It also compares favourably against weighted AODE and hidden Naive Bayes. The learning phase of the new approach is slower than that of its competitors, while the time complexity for the testing phase is similar. Such characteristics suggest that the new classifier is ideal in scenarios where online learning is not required.

  10. Incidence and Predictors of Antiretroviral Treatment Modification in HIV-Infected Adults: A Brazilian Historical Cohort from 2001 to 2010

    Science.gov (United States)

    Pinto Mendicino, Cássia Cristina; Reis, Edna Afonso; Carmo, Ricardo Andrade; Menezes de Pádua, Cristiane

    2017-01-01

    This study estimated the incidence of and time to first antiretroviral therapy (ART) modification. This longitudinal analysis comprised a sample of 236 patients from three HIV/AIDS referral centers in Belo Horizonte, Brazil—part of a major historical cohort. Inclusion criteria were as follows: having been treatment-naive patient ≥18 years old who initiated ART between 2001 and 2005 in these three referral centers. The main endpoint was time to first ART modification. Patients were followed up for five years, covering the period 2001–2010, during which time Pearson's chi-square test was performed to compare ART modification between groups. Kaplan-Meier inverse survival curves were employed to describe the probability of ART modification and Cox proportional hazard regression was used to estimate the adjusted hazard ratio (aHR) of ART modification. Among 247 patients from the major cohort, 236 were eligible. Median follow-up time was 37.2 months and the contribution in person-months was 7,615.4 months. A total of 108 (45.8%) patients had their ART regimen modified at least once (incidence rate: 1.42 per 100 person-months). Adverse drug reactions were the main reason for ART modification. Women (aHR = 1.62; p = 0.022) and patients on protease inhibitor- (PI-) based regimens (aHR = 2.70; p < 0.001) were at higher risk of ART modification.

  11. Subtrochanteric fractures in bisphosphonate-naive patients

    DEFF Research Database (Denmark)

    Adachi, Jonathan D; Lyles, Kenneth; Boonen, Steven

    2011-01-01

    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained ...

  12. Seroprotection of HIV-infected subjects after influenza A(H1N1) vaccination is directly associated with baseline frequency of naive T cells.

    Science.gov (United States)

    Ramirez, Lorenzo A; Daniel, Alexander; Frank, Ian; Tebas, Pablo; Boyer, Jean D

    2014-08-15

    Human immunodeficiency virus type 1 (HIV-1)-infected individuals, despite receipt of antiretroviral therapy (ART), often have impaired vaccine responses. We examined the role that immune activation and cellular phenotypes play in influenza A(H1N1) vaccine responsiveness in HIV-infected subjects receiving ART. Subjects received the H1N1 vaccine (15-µg dose; Novartis), and antibody titers at baseline and after immunization were evaluated. Subjects were classified as responders if, by week 3, seroprotection guidelines were met. Responders had higher percentages of baseline naive T cells and lower percentages of terminally differentiated T cells, compared with nonresponders. Additionally, the naive CD4(+) T-cell percentage and age were negatively correlated. Preservation of naive T-cell populations by starting therapy early could impact vaccine responses against influenza virus and other pathogens, especially as this population ages.

  13. Anthropometric measurements and lipid profiles to detect early lipodystrophy in antiretroviral therapy experienced HIV-infected children in the CHAPAS-3 trial

    NARCIS (Netherlands)

    Musiime, V.; Cook, A.; Kayiwa, J.; Zangata, D.; Nansubuga, C.; Arach, B.; Kenny, J.; Wavamunno, P.; Komunyena, J.; Kabamba, D.; Asiimwe, A.R.; Mirembe, G.; Abongomera, G.; Mulenga, V.; Kekitiinwa, A.; Kityo, C.; Walker, S.A.; Klein, N.; Gibb, D.M.; Burger, D.M.; Fillekes, Q.

    2014-01-01

    BACKGROUND: Few studies have investigated objective markers of lipodystrophy in African children. We compared body circumferences, skin-fold thickness (SFT) and lipids in antiretroviral therapy (ART)-naive and stavudine (d4T)-exposed children with HIV-uninfected controls. METHODS: In the CHAPAS-3 tr

  14. Antiretrovirals for developing world.

    Science.gov (United States)

    Adler, M W

    1998-01-24

    The most recent UNAIDS figures indicate that approximately 30 million people are infected with HIV worldwide, 5.8 million of whom were newly infected during 1997. At the 10th International Conference on AIDS and Sexually Transmitted Diseases in Africa, the President and Secretary of Health of France called upon developed countries to establish a Therapeutic Assistance Fund to make antiretrovirals available to people with HIV/AIDS in sub-Saharan Africa. While the annual per capita health budget in most African countries is less than US$10, triple antiretroviral therapy against AIDS in the developed world costs $12,000-14,000 per patient per year. Calculations based upon a lower per patient cost of $7000, and treating all 1.4 million African AIDS cases, would cost US$10 billion per year for drugs alone, more than 30 times the amount currently spent annually by international donors for AIDS programs in the entire developing world. Basic infrastructural requirements would have to be met were antiretrovirals made widely available, ranging from HIV screening and counseling to the provision of clean water with which to consume the required 20-30 tablets per day. High program costs will challenge long-term sustainability. Universal access to care and treatment for HIV infection and AIDS is not a reality in the developed world, let alone feasible in developing countries. Given the competing health care priorities in developing countries, the high costs of antiretroviral agents, poor infrastructure, and inability to sustain such a program, the French initiative is ill-advised and foolish public health practice.

  15. Mitochondrial toxicity in HIV-infected patients both off and on antiretroviral treatment: a continuum or distinct underlying mechanisms?

    Science.gov (United States)

    Maagaard, Anne; Kvale, Dag

    2009-11-01

    Mitochondrial toxicity contributes to serious adverse effects observed in HIV-infected individuals treated with nucleoside reverse transcriptase inhibitors (NRTIs). However, similar mitochondrial abnormalities have recently been found even in treatment-naive patients, suggesting that chronic HIV per se could contribute to the toxicity observed in NRTI-exposed individuals. This review gives a current status of the field, with particular focus on recent observations suggesting that distinct mechanisms might cause such toxicity in both NRTI-exposed individuals and those naive to antiretroviral treatment.

  16. Personality.

    Science.gov (United States)

    Funder, D C

    2001-01-01

    Personality psychology is as active today as at any point in its history. The classic psychoanalytic and trait paradigms are active areas of research, the behaviorist paradigm has evolved into a new social-cognitive paradigm, and the humanistic paradigm is a basis of current work on cross-cultural psychology. Biology and evolutionary theory have also attained the status of new paradigms for personality. Three challenges for the next generation of research are to integrate these disparate approaches to personality (particularly the trait and social-cognitive paradigms), to remedy the imbalance in the person-situation-behavior triad by conceptualizing the basic properties of situations and behaviors, and to add to personality psychology's thin inventory of basic facts concerning the relations between personality and behavior.

  17. Yugoslav Naive Art and Popular Culture

    Directory of Open Access Journals (Sweden)

    Meta Kordiš

    2009-12-01

    After the Second World War, the Yugoslav socialist state also strove to equalize and democratize society through art by minimizing the differences between the producers and consumers of art. Such a policy led to the decentralization of culture by forming various cultural and artistic institutions and by holding cultural events and spectacles in the countryside and peripheral areas. Through these various informal ideological mechanisms, the state apparatus exercised its authority in socializing its people in the spirit of Yugoslav socialist self-management and the ideology of brotherhood and unity by joining together the producers and consumers of naive art from various ethnicities, cultures, and social classes. Unfortunately this transformed naive art at its peak of popularity into a decorative and souvenir artifact with a pastoral image and folklore motifs. The encouragement from the authorities on the one hand and the market on the other produced and reproduced simple art forms and narrative contents without a complex iconography, which were consumed uncritically and on a large scale. Consequently, this completely denied the core of naive art and resulted in its final devaluation.

  18. CD4+ Count-Guided Interruption of Antiretroviral Treatment. The Strategies for Mangement of Antiretroviral Therapy (SMART) Study Group

    DEFF Research Database (Denmark)

    El-Sadr, WM; Lundgren, Jens Dilling; Neaton, JD

    2006-01-01

    BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV wh...

  19. Increases in pediatric antiretroviral treatment, South Africa 2005-2010.

    Directory of Open Access Journals (Sweden)

    Sandeep D Patel

    Full Text Available BACKGROUND: In South Africa in 2010, about 340,000 children under the age of 15 were infected with HIV. We describe the increase in the treatment of South African pediatric HIV-infected patients assisted by the President's Emergency Plan for AIDS Relief (PEPFAR from 2004 to 2010. METHODS: We reviewed routine program data from PEPFAR-funded implementing partners among persons receiving antiretroviral treatment age 15 years old and less. Data quality was assessed during the reporting period by program officials through routine analysis of trends and logic checks. Based on UNAIDS estimated mortality rates of untreated HIV-infected children, we calculated the number of deaths averted and life-years gained in children under five receiving PEPFAR-assisted antiretroviral treatment. RESULTS: From October 2004 through September 2010, the number of children newly initiated on antiretroviral treatment in PEPFAR-assisted programs increased from 154 to 2,641 per month resulting in an increase from 2,412 children on antiretroviral treatment in September 2005 to 79,416 children in September 2010. Of those children who initiated antiretroviral treatment before September 2009, 0-4 year olds were 1.4 (95% CI: 1.3-1.5 times as likely to transfer out of the program or die as 5-14 year olds; males were 1.3 (95% CI: 1.0-1.7 times as likely to stop treatment as females. Approximately 27,548 years of life were added to children under-five years old from PEPFAR-assisted antiretroviral treatment. CONCLUSIONS: Pediatric antiretroviral treatment in South Africa has increased substantially. However, additional case-finding and a further acceleration in the implementation of pediatric care and treatment services is required to meet the current treatment need.

  20. HIV-2 integrase variation in integrase inhibitor-naive adults in Senegal, West Africa.

    Directory of Open Access Journals (Sweden)

    Geoffrey S Gottlieb

    Full Text Available BACKGROUND: Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance. METHODS: We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1. RESULTS: No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155. Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein. CONCLUSION: Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients.

  1. Do the Naive Know Best? The Predictive Power of Naive Ratings of Couple Interactions

    Science.gov (United States)

    Baucom, Katherine J. W.; Baucom, Brian R.; Christensen, Andrew

    2012-01-01

    We examined the utility of naive ratings of communication patterns and relationship quality in a large sample of distressed couples. Untrained raters assessed 10-min videotaped interactions from 134 distressed couples who participated in both problem-solving and social support discussions at each of 3 time points (pre-therapy, post-therapy, and…

  2. Search for naive human pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Simone Aparecida Siqueira Fonseca; Roberta Montero Costas; Lygia Veiga Pereira

    2015-01-01

    Normal mouse pluripotent stem cells were originallyderived from the inner cell mass (ICM) of blastocystsand shown to be the in vitro equivalent of those preimplantationembryonic cells, and thus were calledembryonic stem cells (ESCs). More than a decade later,pluripotent cells were isolated from the ICM of humanblastocysts. Despite being called human ESCs, thesecells differ significantly from mouse ESCs, includingdifferent morphology and mechanisms of control ofpluripotency, suggesting distinct embryonic originsof ESCs from the two species. Subsequently, mousepluripotent stem cells were established from the ICMderivedepiblast of post-implantation embryos. Thesemouse epiblast stem cells (EpiSCs) are morphologicaland epigenetically more similar to human ESCs. Thisraised the question of whether cells from the humanICM are in a more advanced differentiation stage thantheir murine counterpart, or whether the availableculture conditions were not adequate to maintain thosehuman cells in their in vivo state, leading to a transitioninto EpiSC-like cells in vitro . More recently, novel cultureconditions allowed the conversion of human ESCs intomouse ESC-like cells called naive (or ground state)human ESCs, and the derivation of naive human ESCsfrom blastocysts. Here we will review the characteristicsof each type of pluripotent stem cells, how (andwhether) these relate to different stages of embryonicdevelopment, and discuss the potential implications ofnaive human ESCs in research and therapy.

  3. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer...

  4. Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study.

    Science.gov (United States)

    Carlson, Renee Donahue; Rolfes, Melissa A; Birkenkamp, Kate E; Nakasujja, Noeline; Rajasingham, Radha; Meya, David B; Boulware, David R

    2014-06-01

    Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n = 100). Comparison was made with an HIV-infected, non-meningitis cohort (n = 110). Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P = 0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P = 0.002). Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome.

  5. Vitalistic causality in young children's naive biology.

    Science.gov (United States)

    Inagaki, Kayoko; Hatano, Giyoo

    2004-08-01

    One of the key issues in conceptual development research concerns what kinds of causal devices young children use to understand the biological world. We review evidence that children predict and interpret biological phenomena, especially human bodily processes, on the basis of 'vitalistic causality'. That is, they assume that vital power or life force taken from food and water makes humans active, prevents them from being taken ill, and enables them to grow. These relationships are also extended readily to other animals and even to plants. Recent experimental results show that a majority of preschoolers tend to choose vitalistic explanations as most plausible. Vitalism, together with other forms of intermediate causality, constitute unique causal devices for naive biology as a core domain of thought.

  6. Fuzzy Naive Bayesian for constructing regulated network with weights.

    Science.gov (United States)

    Zhou, Xi Y; Tian, Xue W; Lim, Joon S

    2015-01-01

    In the data mining field, classification is a very crucial technology, and the Bayesian classifier has been one of the hotspots in classification research area. However, assumptions of Naive Bayesian and Tree Augmented Naive Bayesian (TAN) are unfair to attribute relations. Therefore, this paper proposes a new algorithm named Fuzzy Naive Bayesian (FNB) using neural network with weighted membership function (NEWFM) to extract regulated relations and weights. Then, we can use regulated relations and weights to construct a regulated network. Finally, we will classify the heart and Haberman datasets by the FNB network to compare with experiments of Naive Bayesian and TAN. The experiment results show that the FNB has a higher classification rate than Naive Bayesian and TAN.

  7. Accessing antiretroviral therapy for children: Caregivers' voices

    Directory of Open Access Journals (Sweden)

    Margaret (Maggie Williams

    2016-12-01

    Full Text Available Despite efforts to scale up access to antiretroviral therapy (ART, particularly at primary health care (PHC facilities, antiretroviral therapy (ART continues to be out of reach for many human immunodeficiency virus (HIV-positive children in sub-Saharan Africa. In resource limited settings decentralisation of ART is required to scale up access to essential medication. Traditionally, paediatric HIV care has been provided in tertiary care facilities which have better human and material resources, but limited accessibility in terms of distance for caregivers of HIV-positive children. The focus of this article is on the experiences of caregivers whilst accessing ART for HIV-positive children at PHC (decentralised care facilities in Nelson Mandela Bay (NMB in the Eastern Cape, South Africa. A qualitative, explorative, descriptive and contextual research design was used. The target population comprised caregivers of HIV-positive children. Data were collected by means of in-depth individual interviews, which were thematically analysed. Guba's model was used to ensure trustworthiness. Barriers to accessing ART at PHC clinics for HIV-positive children included personal issues, negative experiences, lack of support and finance, stigma and discrimination. The researchers recommend standardised programmes be developed and implemented in PHC clinics to assist in providing treatment, care and support for HIV-positive children.

  8. Cardiovascular risks of antiretroviral therapies.

    Science.gov (United States)

    Mondy, Kristin; Tebas, Pablo

    2007-01-01

    The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.

  9. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

    NARCIS (Netherlands)

    A. Mocroft; O. Kirk; P. Reiss; S. de Wit; D. Sedlacek; M. Beniowski; J. Gatell; A.N. Phillips; B. Ledergerber; J.D. Lundgren

    2010-01-01

    Objectives: Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD. Design: A cohort study including 6843 HIV-positive persons with at le

  10. HIV type 1 integrase polymorphisms in treatment-naive and treatment-experienced HIV type 1-infected patients in Thailand where HIV type 1 subtype A/E predominates.

    Science.gov (United States)

    Phuphuakrat, Angsana; Pasomsub, Ekawat; Kiertiburanakul, Sasisopin; Chantratita, Wasun; Sungkanuparph, Somnuek

    2012-08-01

    Integrase inhibitor (INI) is a novel antiretroviral drug recommended for both treatment-naive and treatment-experienced HIV-1-infected patients. Limited data are available on INI resistance in Thailand, where HIV-1 subtype A/E predominates. We aimed to investigate INI resistance-associated mutations (RAMs) among treatment-naive patients and patients who experienced treatment failure with NNRTI-based or PI-based antiretroviral therapy (ART) in Thailand. One hundred and eight plasma samples of 58 treatment-naive and 50 treatment-experienced HIV-1-infected individuals were collected. The HIV-1 integrase coding region was sequenced. Polymorphisms were compared between subtype A/E and B circulating in Thailand and between treatment-naive and treatment-experienced groups. Resulting amino acids were interpreted for drug resistance according to Stanford algorithms. Ninety-seven samples were HIV-1 subtype A/E, 10 were subtype B, and one was subtype C. Age, gender, and CD4 cell counts were similar between treatment-naive and treatment-experienced groups, while the treatment-failure group showed a statistically significant longer awareness time of HIV-1 infection and lower viral load than the treatment-naive group. Major INI-RAM was not found in this study, but some minor INI-RAMs, such asV54I, L68I, L74M, T97A, and S230N, were found. Comparing INI-RAMs between subtype A/E and B, the prevalence of V54I and V72I was higher in subtype B than subtype E, while V201I was found in all sequences of subtype A/E. In subtype A/E, integrase polymorphisms were not different between treatment-naive and treatment-experienced groups. However, the number of amino acid substitutions was significantly higher in the treatment-experienced group (p=0.009). One NNRTI-based ART-treated patient was found to have potential low-level INI-RAMs. INI-RAMs are rare in both treatment-naive and treatment-experienced patients in Thailand. This suggested that INI should be active in patients who are naive to

  11. High Early Mortality in Patients with Chronic Acquired Immunodeficiency Syndrome Diarrhea Initiating Antiretroviral Therapy in Haiti: A Case-Control Study

    OpenAIRE

    Dillingham, Rebecca A.; Pinkerton, Relana; Leger, Paul; Severe, Patrice; Guerrant, Richard L.; Pape, J. William; Fitzgerald, Daniel W

    2009-01-01

    This case-control study examines whether chronic diarrhea at initiation of antiretroviral therapy (ART) affects survival of human immunodefiency virus–infected patients. Cases (288) were treatment-naive, non-pregnant, adults with self report of frequent loose stool for > 3 weeks at the time ART was initiated. One-third of patients had an enteric pathogen identified including Cryptosporidium spp., Giardia spp., Isospora belli, Cyclospora cayetanensis, and Entamoeba histolytica. Control patient...

  12. Bridging the gap between antiretroviral access and adherence in Mexico.

    Science.gov (United States)

    Campero, Lourdes; Herrera, Cristina; Kendall, Tamil; Caballero, Marta

    2007-05-01

    The goal in this article is to examine social problems associated with highly active antiretroviral therapy (HAART) adherence in Mexico and the related challenges for Mexican persons living with HIV/AIDS (PLWHAs). The study was conducted from the perspective of infected and affected individuals. The authors completed 64 in-depth interviews with heterosexual male and female PLWHAs, as well as with some key individuals from their social network. Following the principles of grounded theory, they carried out inductive analysis to create codes and organize central themes. The authors identified problems related to accessing HAART and found that conditions for implementing recommendations made in the international literature to improve adherence are poor. The findings highlight the importance of social factors, such as health care system irregularities, ineffective physician-patient communication, and availability of family and other sources of social support such as self-help groups for PLWHAs' access and adherence to antiretroviral therapy in Mexico.

  13. Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Clotet, Bonaventura;

    2008-01-01

    OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients...... with detection of TDR, with virological (viral loador=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological suppression......-naive patients was found to be in line with other European studies. No significant differences were found in virological and CD4 count response after initiation of first-line combination antiretroviral therapy between resistant and susceptible patients, possibly due to the small number of patients...

  14. Derivation of novel human ground state naive pluripotent stem cells.

    Science.gov (United States)

    Gafni, Ohad; Weinberger, Leehee; Mansour, Abed AlFatah; Manor, Yair S; Chomsky, Elad; Ben-Yosef, Dalit; Kalma, Yael; Viukov, Sergey; Maza, Itay; Zviran, Asaf; Rais, Yoach; Shipony, Zohar; Mukamel, Zohar; Krupalnik, Vladislav; Zerbib, Mirie; Geula, Shay; Caspi, Inbal; Schneir, Dan; Shwartz, Tamar; Gilad, Shlomit; Amann-Zalcenstein, Daniela; Benjamin, Sima; Amit, Ido; Tanay, Amos; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H

    2013-12-12

    Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3β signalling (termed 2i/LIF conditions). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation X chromosome state, and global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters. Upon withdrawal of 2i/LIF, naive mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast. Although human ES cells share several molecular features with naive mouse ES cells, they also share a variety of epigenetic properties with primed murine epiblast stem cells (EpiSCs). These include predominant use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalent domain acquisition on lineage regulatory genes. The feasibility of establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in mouse ES cells remains to be defined. Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem (iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation

  15. History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; Ledergerber, B

    2010-01-01

    OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategies....... METHODS: A total of 1827 patients on cART starting at least one new antiretroviral from 1 January 2000 while maintaining a suppressed viral load were included in the analysis. Poisson regression analysis identified factors predictive of virological failure after baseline in addition to traditional...... demographic variables. Baseline was defined as the date of starting new antiretrovirals. RESULTS: Four hundred and fifty-one patients (24.7%) experienced virological failure, with an incidence rate (IR) of 7.3 per 100 person-years of follow-up (PYFU) [95% confidence interval (CI) 6.7-8.0]. After adjustment...

  16. Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings

    DEFF Research Database (Denmark)

    Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette;

    2002-01-01

    In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size and predict......In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size...... and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR...

  17. Fault Diagnosis for Fuel Cell Based on Naive Bayesian Classification

    Directory of Open Access Journals (Sweden)

    Liping Fan

    2013-07-01

    Full Text Available Many kinds of uncertain factors may exist in the process of fault diagnosis and affect diagnostic results. Bayesian network is one of the most effective theoretical models for uncertain knowledge expression and reasoning. The method of naive Bayesian classification is used in this paper in fault diagnosis of a proton exchange membrane fuel cell (PEMFC system. Based on the model of PEMFC, fault data are obtained through simulation experiment, learning and training of the naive Bayesian classification are finished, and some testing samples are selected to validate this method. Simulation results demonstrate that the method is feasible.    

  18. Theory-Driven Science and Naive Empiricism in Counseling Psychology.

    Science.gov (United States)

    Strong, Stanley R.

    1991-01-01

    Asserts that counseling psychologists' aversion to theory-driven science and their enthusiasm for naive empiricism impede scientific progress. Identifies "received view" of science as theory-driven science, points out symptoms and consequences of the failure to apply this view, and argues that greater scientific progress will result from moving…

  19. Thinking Process of Naive Problem Solvers to Solve Mathematical Problems

    Science.gov (United States)

    Mairing, Jackson Pasini

    2017-01-01

    Solving problems is not only a goal of mathematical learning. Students acquire ways of thinking, habits of persistence and curiosity, and confidence in unfamiliar situations by learning to solve problems. In fact, there were students who had difficulty in solving problems. The students were naive problem solvers. This research aimed to describe…

  20. Children's Conceptions of Mental Illness: A Naive Theory Approach

    Science.gov (United States)

    Fox, Claudine; Buchanan-Barrow, Eithne; Barrett, Martyn

    2010-01-01

    This paper reports two studies that investigated children's conceptions of mental illness using a naive theory approach, drawing upon a conceptual framework for analysing illness representations which distinguishes between the identity, causes, consequences, curability, and timeline of an illness. The studies utilized semi-structured interviewing…

  1. A Workshop for High School Students on Naive Set Theory

    Science.gov (United States)

    Wegner, Sven-Ake

    2014-01-01

    In this article we present the prototype of a workshop on naive set theory designed for high school students in or around the seventh year of primary education. Our concept is based on two events which the author organized in 2006 and 2010 for students of elementary school and high school, respectively. The article also includes a practice report…

  2. Expert and Naive Raters Using the PAG: Does it Matter?

    Science.gov (United States)

    Cornelius, Edwin T.; And Others

    1984-01-01

    Questions the observed correlation between job experts and naive raters using the Position Analysis Questionnaire (PAQ); and conducts a replication of the Smith and Hakel study (1979) with college students (N=39). Concluded that PAQ ratings from job experts and college students are not equivalent and therefore are not interchangeable. (LLL)

  3. A clinically prognostic scoring system for patients receiving highly active antiretroviral therapy: results from the EuroSIDA study

    DEFF Research Database (Denmark)

    Lundgren, Jens Dilling; Mocroft, Amanda; Gatell, Jose M;

    2002-01-01

    The risk of clinical progression for human immunodeficiency virus (HIV)-infected persons receiving treatment with highly active antiretroviral therapy (HAART) is poorly defined. From an inception cohort of 8457 HIV-infected persons, 2027 patients who started HAART during prospective follow-up wer...

  4. HIV-1 genetic diversity and antiretroviral drug resistance among individuals from Roraima state, northern Brazil

    Science.gov (United States)

    Leão, Renato Augusto Carvalho; Granja, Fabiana; Naveca, Felipe Gomes

    2017-01-01

    The HIV-1 epidemic in Brazil has spread towards the Northern country region, but little is known about HIV-1 subtypes and prevalence of HIV strains with resistance mutations to antiretrovirals in some of the Northern states. HIV-1 protease (PR) and reverse transcriptase (RT) sequences were obtained from 73 treatment-naive and -experienced subjects followed between 2013 and 2014 at a public health reference unit from Roraima, the northernmost Brazilian state. The most prevalent HIV-1 clade observed in the study population was the subtype B (91%), followed by subtype C (9%). Among 12 HIV-1 strains from treatment-naïve patients, only one had a transmitted drug resistance mutation for NNRTI. Among 59 treatment-experienced patients, 12 (20%) harbored HIV-1 strains with acquired drug resistance mutations (ADRM) that reduce the susceptibility to two classes of antiretroviral drugs (NRTI and NNRTI or NRTI and PI), and five (8%) harbored HIV-1 strains with ADRM that reduced susceptibility to only one class of antiretroviral drugs (NNRTI or PI). No patients harboring HIV strains with reduced susceptibility to all three classes of antiretroviral drugs were detected. A substantial fraction of treatment-experienced patients with (63%) and without (70%) ADRM had undetectable plasma viral loads (<40 copies/ml) at the time of sampling. Among treatment-experienced with plasma viral loads above 2,000 copies/ml, 44% displayed no ADRM. This data showed that the HIV-1 epidemic in Roraima displayed a much lower level of genetic diversity and a lower prevalence of ADRM than that described in other Brazilian states. PMID:28301548

  5. Immunovirological Efficacy of Once-Daily Maraviroc Plus Ritonavir-Boosted Atazanavir After 48 Weeks in Naive HIV-Infected Patients.

    Science.gov (United States)

    Pulido, Ildefonso; Genebat, Miguel; Alvarez-Rios, Ana I; De Pablo-Bernal, Rebeca S; Rafii-El-Idrissi Benhnia, Mohammed; Pacheco, Yolanda M; Ruiz-Mateos, Ezequiel; Leal, Manuel

    2016-10-01

    Toxicities related to the use of nucleoside analogues have increased the interest in developing nucleoside-sparing regimens, mainly combining protease inhibitors with raltegravir. However, data regarding the use of CCR5-antagonists in this setting and in the naive scenario are scarce. The main objective was to analyze the immunovirological efficacy and tolerability of a low-dose, once-daily, maraviroc (MVC)-containing, nucleoside reverse transcriptase inhibitor-sparing dual therapy compared with standard triple therapy after 48 weeks for naive HIV-infected patients in the routine clinical practice setting. All naive HIV-infected patients with stable clinical condition that started antiretroviral treatment since February 1, 2008 to May 30,h 2012 were included. MVC clinical test was used to select candidate subjects to MVC therapy. Thirty-two subjects with MVC + atazanavir/ritonavir (ATV/r) and 66 with standard triple therapy were analyzed. A comparable virological efficacy between groups was found after 48 weeks (87.5% vs. 80.3% of HIV undetectability, p = 0.37, MVC + ATV/r and triple therapy groups, respectively). The CD4 recovery after 48 weeks was similar and more than 200 cells/mm(3) in both groups. No need of therapy changes or treatment discontinuations was observed in the MVC + ATV/r group. Effect on lipid profile, high-sensitivity C reactive protein, and β2-microglobulin was similar for both groups. Noteworthy, a significant increase of erythrocyte mean corpuscular volume was observed only in the triple therapy group. A nucleoside-sparing MVC-containing dual therapy showed similar immunovirological efficacy and tolerability than standard triple therapy in naive HIV-infected patients.

  6. Antiretroviral procurement and supply chain management.

    Science.gov (United States)

    Ripin, David J; Jamieson, David; Meyers, Amy; Warty, Umesh; Dain, Mary; Khamsi, Cyril

    2014-01-01

    Procurement, the country-level process of ordering antiretrovirals (ARVs), and supply chain management, the mechanism by which they are delivered to health-care facilities, are critical processes required to move ARVs from manufacturers to patients. To provide a glimpse into the ARV procurement and supply chain, the following pages provide an overview of the primary stakeholders, principal operating models, and policies and regulations involved in ARV procurement. Also presented are key challenges that need to be addressed to ensure that the supply chain is not a barrier to the goal of universal coverage. This article will cover the steps necessary to order and distribute ARVs, including different models of delivery, key stakeholders involved, strategic considerations that vary depending on context and policies affecting them. The single drug examples given illustrate the complications inherent in fragmented supply and demand-driven models of procurement and supply chain management, and suggest tools for navigating these hurdles that will ultimately result in more secure and reliable ARV provision. Understanding the dynamics of ARV supply chain is important for the global health community, both to ensure full and efficient treatment of persons living with HIV as well as to inform the supply chain decisions for other public health products.

  7. File list: Oth.Bld.10.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.AllAg.Naive_T_cells hg19 TFs and others Blood Naive T cells SRX1425808 h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.10.AllAg.Naive_T_cells.bed ...

  8. File list: Oth.Bld.50.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.AllAg.Naive_T_cells hg19 TFs and others Blood Naive T cells SRX1425808 h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.50.AllAg.Naive_T_cells.bed ...

  9. File list: Oth.Bld.05.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.AllAg.Naive_T_cells hg19 TFs and others Blood Naive T cells SRX1425808 h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.05.AllAg.Naive_T_cells.bed ...

  10. File list: Oth.Bld.20.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.AllAg.Naive_T_cells hg19 TFs and others Blood Naive T cells SRX1425808 h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.20.AllAg.Naive_T_cells.bed ...

  11. File list: ALL.Bld.10.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.Naive_T_cells hg19 All antigens Blood Naive T cells SRX1425815,SRX...1425816,SRX1425814,SRX1425808 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.10.AllAg.Naive_T_cells.bed ...

  12. Abacavir/Lamivudine/Zidovudine Maintenance After Standard Induction in Antiretroviral Therapy-Naive Patients : FREE Randomized Trial Interim Results

    NARCIS (Netherlands)

    Sprenger, Herman G.; Langebeek, Nienke; Mulder, Paul G. H.; Ten Napel, Chris H. H.; Vriesendorp, Robert; Hoepelman, Andy I. M.; Legrand, Jean-Claude; Koopmans, Peter P.; Van Kasteren, Marjo E. E.; Bravenboer, Bert; Ten Kate, Reinier W.; Groeneveld, Paul H. P.; Van der Werf, Tjip S.; Gisolf, Elisabeth H.; Richter, Clemens

    2010-01-01

    Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-relate

  13. Effect of micronutrient and probiotic fortified yogurt on immune-function of anti-retroviral therapy naive HIV patients

    NARCIS (Netherlands)

    R.B.S. Hummelen (Ruben); J. Hemsworth (Jaimie); J. Changalucha (John); N.L. Butamanya (Nicodemus); S. Hekmat (Sharareh); J.D.F. Habbema (Dik); G. Reid (Gregor)

    2011-01-01

    textabstractBackground: Micronutrient supplementation has been shown to reduce the progression of HIV but does not have an effect on the intestinal barrier or the intestinal microbiota of HIV patients. Studies have suggested that probiotics could potentially complement micronutrients in preserving t

  14. Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.

    Directory of Open Access Journals (Sweden)

    Rami Kantor

    2005-04-01

    Full Text Available BACKGROUND: The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. METHODS AND FINDINGS: To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80% of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. CONCLUSION: Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

  15. Acquiring a naive theory of kinship through inference.

    Science.gov (United States)

    Springer, K

    1995-04-01

    The present study focused on how children acquire a naive theory of kinship. Young children appear to have theoretical beliefs about the biological meaning of kinship relations. It was argued here that these beliefs reflect inductive inferences from simple facts about prenatal growth (e.g, where babies grow). An informal model of the inferences linking facts to theory was proposed and tested. In Experiment 1, 4-7-year-olds who knew the basic facts of prenatal growth were most likely to also express the naive theory of kinship. Virtually none of the children who expressed the theory were unaware of the basic facts. In Experiment 2, teaching the facts to a sample of preschoolers led to some increase in their acceptance of the kinship theory. Overall, the results implicate a type of theory building that involves inferences from preexisting knowledge rather than structural change, use of analogy, or acquisition of new knowledge.

  16. Children's naive theories of intelligence influence their metacognitive judgments.

    Science.gov (United States)

    Miele, David B; Son, Lisa K; Metcalfe, Janet

    2013-01-01

    Recent studies have shown that the metacognitive judgments adults infer from their experiences of encoding effort vary in accordance with their naive theories of intelligence. To determine whether this finding extends to elementary schoolchildren, a study was conducted in which 27 third graders (M(age) = 8.27) and 24 fifth graders (M(age) = 10.39) read texts presented in easy- or difficult-to-encode fonts. The more children in both grades viewed intelligence as fixed, the less likely they were to interpret effortful or difficult encoding as a sign of increasing mastery and the more likely they were to report lower levels of comprehension as their perceived effort increased. This suggests that children may use naive theories of intelligence to make motivationally relevant inferences earlier than previously thought.

  17. Note---Naive Diversification and Portfolio Risk---A Note

    OpenAIRE

    Ron Bird; Mark Tippett

    1986-01-01

    A number of authors have used the portfolio standard deviation to model the risk reduction advantages of naive diversification. Other authors have pointed out that when risk is modelled by the portfolio's variance the modelling process becomes much simpler and is computationally more efficient. In this note we derive an exact parametric relationship between portfolio standard deviation and size and thus highlight the dangers of using the standard deviation in conjunction with O.L.S. regressio...

  18. Incidence of tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America

    NARCIS (Netherlands)

    Costagliola, D; Dabis, F; Monforte, AD; de Wolf, F; Egger, M; Fatkenheuer, G; Gill, J; Hogg, R; Justice, A; Ledergerber, B; Lundgren, J; May, M; Phillips, A; Reiss, P; Sabin, C; Staszewski, S; Sterne, J; Weller, H.H.; May, M; Beckthold, B; Yip, B; Dauer, B; Fusco, J; Grabar, S; Lanoy, E; Junghans, C; Lavignolle, V.; van Leth, F; Pereira, E; Pezzotti, P; Phillips, A; Sabin, C; Schmeisser, N; Billaud, E; Boue, F; Duval, J.; Duvivier, C; Enel, P; Fournier, S; Gasnault, J; Gaud, C; Gilquin, J; Grabar, S; Khuong, MA; Lang, JM; Mary-Krause, M; Matheron, S; Meyohas, MC; Pialoux, G; Poizot-Martin, I.; Pradier, C; Rouveix, E; Salmon-Ceron, D; Sobel, A; Tattevin, P; Tissot-Dupont, H; Yasdanpanah, Y; Aronica, E; Tirard-Fleury, V.; Tortay, I.; Abgrall, S; Guiguet, M; Leneman, H; Lievre, L; Potard, V.; Saidi, S; Matheron, S; Vilde, JL; Leport, C; Yeni, P; Bouvet, E; Gaudebout, C; Crickx, B; Picard-Dahan, C; Weiss, L; Tisne-Dessus, D; Sicard, D; Salmon, D; Auperin, A; Viard, JP; Roudiere, L; Delfraissy, JF; Goujard, C; Lesprit, P; Jung, C; Meyohas, MC; Meynard, JL; Picard, O; Desplanque, N; Cadranel, J; Mayaud, C; Rozenbaum, W; Bricaire, F; Katlama, C; Herson, S; Simon, A; Decazes, JM; Molina, JM; Clauvel, JP; Gerard, L; Widal, GHLF; Sellier, P; Diemer, M; Dupont, C; Berthe, H; Saiag, P; Mortier, L; Mortier, E; Chandemerle, C; de Truchis, P; Bentata, M; Honore, P; Tassi, S; Jeantils, V.; Mechali, D; Taverne, B; Laurichesse, H; Gourdon, F; Lucht, F; Fresard, A; Faller, JP; Eglinger, P; Bazin, C; Verdon, R; Peyramond, D; Boibieux, A; Touraine, JL; Livrozet, JM; Trepo, C; Cotte, L; Ravaux, I.; Delmont, JP; Moreau, J; Gastaut, JA; Soubeyrand, J; Retornaz, F; Blanc, PA; Allegre, T; Galinier, A; Ruiz, JM; Lepeu, G; Granet-Brunello, P; Pelissier, L; Esterni, JP; Nezri, M; Cohen-Valensi, R; Laffeuillade, A; Chadapaud, S; Reynes, J; May, T; Rabaud, C; Raffi, F; Pugliese, P; Michelet, C; Arvieux, C; Caron, F; Borsa-Lebas, F; Lang, JM; Fraisse, P; Massip, P; Cuzin, L; Arlet-Suau, E; Legrand, MFT; Yasdanpanah, Y; Sobesky, M; Pradinaud, R; Guyon, F; Contant, M; Montroni, M; Scalise, G; Braschi, MC; Aviano, AR; Tirelli, U; Cinelli, R; Pastore, G; Ladisa, N; Minafra, G; Suter, F; Arici, C; Chiodo, F; Colangeli, V.; Fiorini, C; Coronado, O; Carosi, G; Cadeo, GP; Torti, C; Minardi, C; Bertelli, D; Rizzardini, G; Melzi, S; Manconi, PE; Catanzaro, PP; Cosco, L; Scerbo, A; Vecchiet, J; D'Alessandro, M; Santoro, D; Pusterla, L; Carnevale, G; Citterio, P; Vigano, P; Mena, M; Ghinelli, F; Sighinolfi, L; Leoncini, F; Mazzotta, F; Pozzi, M; Lo Caputo, S; Angarano, G; Grisorio, B; Saracino, A; Ferrara, S; Grima, P; Tundo, P; Pagano, G; Cassola, G; Alessandrini, A; Piscopo, R; Toti, M; Chigiotti, S; Soscia, F; Tacconi, L; Orani, A; Perini, P; Scasso, A; Vincenti, A; Chiodera, F; Castelli, P; Scalzini, A; Palvarini, L; Moroni, M; Lazzarin, A; Cargnel, A; Vigevani, GM; Caggese, L; Monforte, AD; Repetto, D; Galli, A; Merli, S; Pastecchia, C; Moioli, MC; Esposito, R; Mussini, C; Abrescia, N; Chirianni, A; Izzo, CM; Piazza, M; De Marco, M; Viglietti, R; Manzillo, E; Nappa, S; Colomba, A; Abbadessa, V.; Prestileo, T; Mancuso, S; Ferrari, C; Pizzaferri, P; Filice, G; Minoli, L; Bruno, R; Novati, S; Baldelli, F; Tinca, M; Petrelli, E; Cioppi, A; Alberici, F; Ruggieri, A; Menichetti, F; Martinelli, C; De Stefano, C; La Gala, A; Ballardini, G; Rizzo, E; Magnani, G; Ursitti, MA; Arlotti, M; Ortolani, P; Cauda, R; Dianzani, F; Ippolito, G; Antinori, A; Antonucci, G; D'Elia, S; Narciso, P; Petrosillo, N; Vullo, V.; De Luca, A; Bacarelli, A; Zaccarelli, M; Acinapura, R; De Longis, P; Brandi, A; Trotta, MP; Noto, P; Lichtner, M; Capobianchi, MR; Carletti, F; Girardi, E; Pezzotti, P; Rezza, G; Mura, MS; Mannazzu, M; Caramello, P; Di Perri, G; Soranzo, ML; Orofino, GC; Arnaudo, I.; Bonasso, M; Grossi, PA; Basilico, C; Poggio, A; Bottari, G; Raise, E; Ebo, F; De Lalla, F; Tositti, G; Resta, F; Loso, K; Lepri, AC; Battegay, M; Bernasconi, E; Boni, J; Bucher, H; Burgisser, P; Cattacin, S; Cavassini, M; Dubs, R; Egger, M; Elzi, L; Erb, P; Fantelli, K; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, H; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Lauper, U; Ledergerber, B; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schmid, P; Schupbach, J; Speck, R; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Bronsveld, W; Hillebrand-Haverkort, ME; Prins, JM; Bos, JC; Schattenkerk, JKME; Geerlings, SE; Godfried, MH; Lange, JMA; van Leth, FC; Lowe, SH; van der Meer, JTM; Nellen, FJB; Pogany, K; van der Poll, T; Reiss, P; Ruys, TA; Sankatsing, S; Steingrover, R; van Twillert, G; van der Valk, M; van Vonderen, MGA; Vrouenraets, SME; van Vugt, M; Wit, FWMN; Kuijpers, TW; Pajkrt, D; Scherpbier, HJ; van Eeden, A; ten Veen, JH; van Dam, PS; Roos, JC; Brinkman, K; Frissen, PHJ; Weigel, HM; Mulder, JW; van Gorp, ECM; Meenhorst, PL; Mairuhu, ATA; Ziekenhuis, S; Veenstra, J; Danner, SA; van Agtmael, MA; Claessen, FAP; Perenboom, RM; Rijkeboer, A; van Vonderen, M; Richter, C; van der Berg, J; van Leusen, R; Vriesendorp, R; Jeurissen, FJF; Kauffmann, RH; Koger, ELW; Bravenboer, B; ten Napel, CHH; Kootstra, GJ; Sprenger, HG; Miesen, WMAJ; Doedens, Rienus; Scholvinck, EH; ten Kate, RW; van Houte, DPF; Polee, M; Kroon, FP; Broek, van den; van Dissel, JT; Schippers, EF; Schreij, G; de Geest, SV; Verbon, A; Koopmans, PP; Keuter, M; Post, F; van der Ven, AJAM; van der Ende, Marchina E.; Gyssens, IC; van der Feltz, M; den Hollander, JG; de Marie, S; Nouwen, JL; Rijnders, BJA; de Vries, TEMS; Driessen, G; de Groot, R; Hartwig, N; Juttmann, J.; van de Heul, C; van Kasteren, MEE; Schneider, MME; Bonten, MJM; Borleffs, JCC; Ellerbroek, PM; Hoepelman, IM; Jaspers, CAJJ; Schouten, M.C.; Schurink, CAM; Geelen, SPM; Wolfs, TFW; Blok, WL; Tanis, AA; Groeneveld, PHP; Back, NKT; Bakker, MEG; Berkhout, B; Jurriaans, S; Cuijpers, T; Rietra, PJGM; Roozendaal, KJ; Pauw, W; van Zanten, AP; von Blomberg, BME; Savelkoul, P; Swanink, CMA; Franck, PFH; Lampe, AS; Hendriks, R; Schirm, J; Veenendaal, D; Storm, H; Weel, J; van Zeijl, H; Kroes, ACM; Claas, HCJ; Bruggeman, CAMVA; Goossens, VJ; Galama, JMD; Melchers, WJG; Poort, YAG; Doornum, GJJ; Niesters, MG; Osterhaus, ADME; Schutten, M; Buiting, AGM; Swaans, CAM; Boucher, CAB; Boel, E; Jansz, AF; Losso, M; Duran, A; Vetter, N; Karpov, A.; Vassilenko, A; Clumeck, N; De Wit, S; Poll, B; Colebunders, R; Machala, L; Rozsypal, H; Sedlacek, D; Nielsen, J; Lundgren, J; Benfield, T; Kirk, O; Gerstoft, J; Katzenstein, T; Hansen, ABE; Skinhoj, P; Pedersen, C; Zilmer, K; Katlama, C; Girard, PM; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Stellbrink, HJ; Staszewski, S; Bickel, M; Goebel, FD; Fatkenheuer, G; Rockstroh, J; Schmidt, R; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Filandras, A; Karabatsaki, E; Banhegyi, D; Mulcahy, F; Yust, I.; Turner, D; Burke, M; Pollack, S; Hassoun, G; Sthoeger, Z; Maayan, S; Chiesi, A; Esposito, R; Borghi, R; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Lichtner, M; Chirianni, A; Montesarchio, E; Iacomi, F; Lazzarin, A; Finazzi, R; Viksna, L; Chaplinskas, S; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, V.; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Wiercinska-Drapalo, A; Boron-Kaczmarska, A; Pynka, M; Beniowski, M; Mularska, E; Trocha, H; Antunes, F; Valadas, E; Mansinho, K; Matez, F; Duiculescu, D; Babes, V.; Streinu-Cercel, A; Vinogradova, E; Rakhmanova, A; Jevtovic, D; Mokras, M; Stanekova, D; Gonzalez-Lahoz, J; Sanchez-Conde, M; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, Joan B.; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Blaxhult, A; Karlsson, A; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Telenti, A; Hirschel, B; Soravia-Dunand, V.; Furrer, H; Kravchenko, E; Chentsova, N; Barton, S; Johnson, AM; Mercey, D; Phillips, A; Johnson, MA; Mocroft, A; Murphy, M; Weber, J; Scullard, G; Fisher, M; Brettle, R; Loveday, C; Clotet, B; Antunes, F; Blaxhult, A; Clumeck, N; Gatell, J; Horban, A; Johnson, A; Katlama, C; Ledergerber, B; Loveday, C; Phillips, A; Reiss, P; Vella, S; Gjorup, N; Kirk, O; Friis-Moeller, N; Mocroft, A; Cozzi-Lepri, A; Bannister, W; Mollerup, D; Podlevkareva, D; Olsen, CH; Kjaer, J; Raffanti, S; Dieterch, D; Justice, A; Becker, S; Scarsella, A; Fusco, G; Most, B; Balu, R; Rana, R; Beckerman, R; Ising, T; Fusco, J; Irek, R; Johnson, B; Hirani, A; DeJesus, E; Pierone, G; Lackey, P; Irek, C; Johnson, A; Burdick, J; Leon, S; Arch, J; Staszewski, S; Helm, EB; Carlebach, A; Muller, A; Haberl, A; Nisius, G; Lennemann, T; Rottmann, C; Muller, A; Haberl, A; Nisius, G; Lennemann, T; Rottmann, C; Wolf, T; Stephan, C; Bickel, M; Mosch, M; Gute, P; Locher, L; Lutz, T; Klauke, S; Knecht, G; Doerr, HW; Sturmer, M; Dauer, B; von Hentig, N; Jennings, B; Beylot, J; Chene, G; Dabis, F; Dupon, M; Longy-Boursier, M; Pellegrin, JL; Ragnaud, JM; Salamon, R; Dabis, F; Chene, G; Thiebaut, R; Lewden, C; Lawson-Ayayi, S; Dupon, M; Mercie, P; Moreau, JF; Moriat, P; Pellegrin, JL; Ragnaud, JM; Bernard, N; Lacoste, D; Malvy, D; Neau, D; Blaizeau, MJ; Decoin, M; Delveaux, S; Hannapier, C; Labarrere, S; Lavignolle-Aurillac, V.; Uwamaliya-Nziyumvira, B; Palmer, G; Touchard, D; Balestre, E; Alioum, A; Jacqmin-Gadda, H; Thiebaut, R; Beylot, J; Morlat, P; Bernard, N; Bonarek, M; Bonnet, F; Coadou, B; Gellie, P; Lacoste, D; Nouts, C; Dupon, M; Bocquentin, F; Dutronc, H; Lafarie, S; Longy-Boursier, M; Mercie, P; Aslan, A; Malvy, D; Pistonne, T; Thibaut, P; Vatan, R; Ragnaud, JM; Chambon, D; De La Taille, C; Cazorla, C; Neau, D; Ocho, A; Pellegrin, JL; Castera, L; Fleury, H; Lafon, ME; Masquelier, B; Pellegrin, E.; Breilh, D; Moreau, JF; Blanco, P; Loste, P; Caunegre, L; Bonnal, F; Farbos, S; Ferrand, M; Ceccaldi, J; Tchamgoue, S; De Witte, S; Buy, E; Alexander, C; Barrios, R; Braitstein, P; Brumme, Z; Chan, K; Cote, H; Gataric, N; Geller, J; Guillemi, S; Harrigan, K.; Harris, M; Hogg, R; Joy, R; Levy, A; Montaner, J; Montessori, V.; Palepu, A; Phillips, E; Phillips, P; Press, N; Tyndall, M; Wood, E; Yip, B; Ballinger, J; Bhagani, S; Breen, R; Byrne, P; Carroll, A; Cropley, Mark; Cuthbertson, Z; Drinkwater, T; Fernandez, T; Geretti, AM; Murphy, G; Ivens, D; Johnson, M; Kinloch-de Loes, S; Lipman, M; Madge, S; Prinz, B; Bell, DR; Shah, S; Swaden, L; Tyrer, M; Youle, M; Chaloner, C; Gumley, H; Holloway, J; Puradiredja, D; Sweeney, J; Tsintas, R; Bannister, W; Bansi, L; Cozzi-Lepri, A; Fox, Z; Lampe, F; Mocroft, A; Phillips, A; Sabin, C; Smith, C; Amoah, E; Clewley, G; Dann, L; Gregory, B; Jani, I.; Janossy, G; Kahan, M; Loveday, C; Thomas, M; Gill, MJ; Read, R; Fatkenheuer, G; Rockstroh, J; Schmeisser, V.; Voigt, K; Wasmuth, JC; Wohrmann, A

    2005-01-01

    Background. We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HAART and identified determinants of the incidence. Methods. We analyzed the incidence of TB during the first 3 years after initiation of HAART among 17,142 treatment-naive, AIDS- free persons starting H

  19. Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care

    Directory of Open Access Journals (Sweden)

    Angela Cescon

    2015-10-01

    Full Text Available Introduction: Combination antiretroviral therapy (ART significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment. Methods: Participants from the Canadian Observational Cohort (CANOC, a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec were included. Late initiation was defined as a CD4 count <200 cells/mm3 or an AIDS-defining illness before ART initiation (baseline. Temporal trends were assessed using the Cochran–Armitage test, and independent correlates of late initiation were identified using logistic regression. Results: In total, 8942 participants (18% female of median age 40 years (Q1–Q3 33–47 were included. The median baseline CD4 count increased from 190 cells/mm3 (Q1–Q3 80–320 in 2000 to 360 cells/mm3 (Q1–Q3 220–490 in 2012 (p<0.001. Overall, 4274 participants (48% initiated ART with a CD4 count <200 cells/mm3 or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec, persons with injection drug use (IDU history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012 predictors using an updated CD4 criterion (<350 cells/mm3, IDU and residence in BC (vs. Québec were no longer significant correlates of late initiation. Conclusions: This analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.

  20. Disease progresses more quickly in introverts. Shy, inhibited personalities may fare worse.

    Science.gov (United States)

    2004-03-01

    Los Angeles researchers recently have discovered clinical evidence that HIV-positive people with shy and introverted personalities tend to have a faster disease progression and less optimal outcomes under antiretroviral treatment than do people with extroverted personalities.

  1. Intestinal parasitosis in relation to CD4+T cells levels and anemia among HAART initiated and HAART naive pediatric HIV patients in a Model ART center in Addis Ababa, Ethiopia.

    Directory of Open Access Journals (Sweden)

    Hylemariam Mihiretie Mengist

    Full Text Available Intestinal parasites (IPs are major concerns in most developing countries where HIV/AIDS cases are concentrated and almost 80% of AIDS patients die of AIDS-related infections. In the absence of highly active antiretroviral therapy (HAART, HIV/AIDS patients in developing countries unfortunately continue to suffer from the consequences of opportunistic and other intestinal parasites. The aim of the study was to determine the prevalence of intestinal parasites in relation to CD4+ T cells levels and anemia among HAART initiated and HAART naïve pediatric HIV patients in a Model ART center in Addis Ababa, Ethiopia.A prospective comparative cross-sectional study was conducted among HAART initiated and HAART naive pediatric HIV/AIDS patients attending a model ART center at Zewditu Memorial Hospital between August 05, 2013 and November 25, 2013. A total of 180 (79 HAART initiated and 101 HAART naïve children were included by using consecutive sampling. Stool specimen was collected and processed using direct wet mount, formol-ether concentration and modified Ziehl-Neelsen staining techniques. A structured questionnaire was used to collect data on socio-demographic and associated risk factors. CD4+ T cells and complete blood counts were performed using BD FACScalibur and Cell-Dyn 1800, respectively. The data was analyzed by SPSS version 16 software. Logistic regressions were applied to assess any association between explanatory factors and outcome variables. P values < 0.05 were taken as statistically significant.The overall prevalence of IPs was 37.8% where 27.8% of HAART initiated and 45.5% of HAART naive pediatric HIV/AIDS patients were infected (p < 0.05. Cryptosporidium species, E. histolytica/dispar, Hook worm and Taenia species were IPs associated with CD4+ T cell counts <350 cells/μμL in HAART naive patients. The overall prevalence of anemia was 10% in HAART and 31.7% in non-HAART groups. Hook worm, S. stercoralis and H. nana were helminthes

  2. Drug interactions between hormonal contraceptives and antiretrovirals

    Science.gov (United States)

    Nanda, Kavita; Stuart, Gretchen S.; Robinson, Jennifer; Gray, Andrew L.; Tepper, Naomi K.; Gaffield, Mary E.

    2017-01-01

    Objective: To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals. Design: Systematic review of the published literature. Methods: We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses. Results: Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives. Conclusion: Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices. PMID:28060009

  3. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents.

    Science.gov (United States)

    Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

    2002-09-03

    The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general

  4. Triple-Nucleoside Analog Antiretroviral Therapy: Is There Still a Role in Clinical Practice? A Review

    Directory of Open Access Journals (Sweden)

    Kessler Harold A

    2005-06-01

    Full Text Available Abstract The development and widespread clinical use of coformulated abacavir/lamivudine/zidovudine (ABC/3TC/ZDV as Trizivir represented an important advance in the management of HIV-infected patients, especially those with adherence challenges. With a low pill burden, no food restrictions, limited drug-drug interactions, and a favorable resistance profile, ABC/3TC/ZDV remains an alternative option in the US Department of Health and Human Services Consensus Panel Guidelines as initial treatment in antiretroviral-naive patients. Recent data have shown ABC/3TC/ZDV to be less efficacious in suppressing and/or maintaining suppression of virologic replication compared with efavirenz-containing antiretroviral therapy. Although triple-nucleoside/nucleotide reverse transcriptase inhibitor (t-NRTI combinations that do not contain a thymidine analog (ZDV or stavudine have recently shown high virologic failure rates in clinical trials and clinical practice, t-NRTI regimens containing a thymidine analog have consistently been shown to be efficacious.

  5. Opportunistic diseases in HIV-infected patients in Gabon following the administration of highly active antiretroviral therapy: a retrospective study.

    Science.gov (United States)

    Okome-Nkoumou, Madeleine; Guiyedi, Vincent; Ondounda, Magloire; Efire, Nora; Clevenbergh, Philippe; Dibo, Mireille; Dzeing-Ella, Arnaud

    2014-02-01

    Opportunistic diseases cause substantial morbidity and mortality to human immunodeficiency virus (HIV)-infected patients. Highly active antiretroviral therapy (HAART) leading to immune reconstitution is the most effective treatment of preventing opportunistic diseases. This retrospective study established an epidemiologic profile of opportunistic diseases 10 years after the introduction of HAART. The HIV antiretroviral therapy-naive patients matching inclusion criteria were included. The primary outcome was the prevalence of opportunistic diseases. From January 1, 2002 to September 30, 2010, 654 opportunistic diseases were identified in 458 patients. Pulmonary tuberculosis, herpes zoster, cerebral toxoplasmosis, oral candidiasis, and severe pneumonia accounted for 22.05%, 15.94%, 14.19%, 14.19%, and 9.39%, respectively. Cryptococcal meningitis and pneumocystosis accounted for 0.44% and 0.21%, respectively. The prevalence of opportunistic diseases in Gabon remains high. New guidelines emphasize the importance of initiating antiretroviral therapy early to reconstitute the immune system, and reduce disease risk, and treat the primary opportunistic infection of pulmonary tuberculosis.

  6. Prices of second-line antiretroviral treatment for middle-income countries inside versus outside sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Bryony Simmons

    2014-11-01

    Full Text Available Introduction: Antiretrovirals are available at low prices in sub-Saharan Africa, but these prices may not be consistently available for middle-income countries in other regions with large HIV epidemics. Over 30% of HIV infected people live in countries outside sub-Saharan Africa. Several key antiretrovirals are still on patent, with generic production restricted. We assessed price variations for key antiretroviral drugs inside versus outside sub-Saharan Africa. Methods: HIV drug prices used in national programmes (2010–2014 were extracted from the WHO Global Price Reporting Mechanism database for all reporting middle-income countries as classified by the World Bank. Treatment costs (branded and generic were compared for countries inside sub-Saharan Africa versus those outside. Five key second-line antiretrovirals were analysed: abacavir, atazanavir, darunavir, lopinavir/ritonavir, raltegravir. Results: Prices of branded antiretrovirals were significantly higher outside sub-Saharan Africa (p<0.001, adjusted for year of purchase (see Table 1. For example, the median (interquartile range price of darunavir from Janssen was $732 (IQR $732-806 per person-year in sub-Saharan Africa versus $4689 (IQR $4075-5717 in non-African middle-income countries, an increase of 541%. However, when supplied by generic companies, most antiretrovirals were similarly priced between countries in sub-Saharan Africa and other regions. Conclusions: Pharmaceutical companies are selling antiretrovirals to non-African middle-income countries at prices 74–541% higher than African countries with similar gross national incomes. However, generic companies are selling most of these drugs at similar prices across regions. Mechanisms to ensure fair pricing for patented antiretrovirals across both African and non-African middle-income countries need to be improved, to ensure sustainable treatment access.

  7. HIV-1 antiretroviral drug resistance in recently infected patients in Abidjan, Côte d'Ivoire: A 4-year survey, 2002-2006.

    Science.gov (United States)

    Toni, Thomas d'Aquin; Masquelier, Bernard; Minga, Albert; Anglaret, Xavier; Danel, Christine; Coulibaly, Ali; Chenal, Henri; Dabis, François; Salamon, Roger; Fleury, Hervé J

    2007-09-01

    We performed HIV-1 drug resistance genotypic analysis of viral isolates from 100 antiretroviral (ARV)-naive, recently HIV-1-infected (between 2002 and 2006) individuals from Abidjan (Côte d'Ivoire). The overall prevalence of HIV-1 variants with resistance mutations to reverse transcriptase, protease, or fusion inhibitors was 6%. The majority of isolates were CRF02_AG. Compared with a previous study carried out by our group in 2001-2002 in a similar population in Abidjan, our findings confirm the circulation and transmission of HIV-1 carrying key ARV drug resistance mutation.

  8. Poor Efficacy and Tolerability of Stavudine, Didanosine, and Efavirenz-based Regimen in Treatment-Naive Patients in Senegal

    Directory of Open Access Journals (Sweden)

    Canestri Anna

    2007-10-01

    Full Text Available Abstract Objective To study the effectiveness and tolerance of an antiretroviral therapy (ART regimen composed of the antiretroviral agents (ARVs stavudine (d4T plus didanosine (ddI plus efavirenz (EFV in patients with advanced HIV infection in Senegal. Design and methods This was an open-label, single-arm, 18-month trial in treatment-naive patients. The primary virologic end point was the percentage of patients with plasma HIV RNA Results The staging of HIV disease, performed using the definitions of the US Centers for Disease Control and Prevention (CDC, was CDC stage B or C for all 40 recruited patients. At baseline, the mean CD4+ cell count was 133 ± 92/mcL (± standard deviation [SD]; range 1–346, and 23% of patients had CD4+ cell counts below 50/mcL. The mean baseline plasma HIV RNA level was 5.5 ± 0.4 log10 copies/mL (± SD; range 4.6–5.9. The proportion of patients with plasma HIV-1 RNA below 500 copies/mL fell during the study from 73% (95% CI [56; 85] at M6 to 56% (95% CI [41; 73] at M12 and 43% (95% CI [27; 59] at M18. Plasma HIV-RNA was below 50 copies/mL in 50% of study subjects (95% CI [31; 66] at M6, 43% (95% CI [27; 59] at M12, and 33% (95% CI [19; 49] at M18. The mean increase in the CD4+ cell count was 105 ± 125/mcL (n = 38 at M3 and 186 ± 122/mcL (n = 21 at M18. Eight patients died, including 6 because of infectious complications. The last viral load (VL value before death was Conclusion Virologic efficacy combination therapy with d4T, ddI, and EFV was measured by the percentage of patients with plasma HIV RNA values below 500 copies/mL and 50 copies/mL; for both parameters, virologic efficacy decreased during the study period. This is explained by the high mortality rate (20% and treatment modifications due to adverse events (13%. These data strengthen the recently revised World Health Organization (WHO guidelines advocating initiation of highly active antiretroviral therapy (HAART before profound CD4 lymphocyte

  9. Sensory Adaptation in Naive Peripheral CD4 T Cells

    OpenAIRE

    Smith, Katy; Seddon, Benedict; Purbhoo, Marco A.; Zamoyska, Rose; Fisher, Amanda G.; Merkenschlager, Matthias

    2001-01-01

    T cell receptor interactions with peptide/major histocompatibility complex (pMHC) ligands control the selection of T cells in the thymus as well as their homeostasis in peripheral lymphoid organs. Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56lck. Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca2+ responses to subsequent TCR engagement by anti-CD3 or nominal anti...

  10. Emergence of an NNRTI resistance mutation Y181C in an HIV-infected NNRTI-naive patient.

    Science.gov (United States)

    Magiorkinis, Emmanouil; Paraskevis, Dimitrios; Sambatakou, Helen; Gargalianos, Panagiotis; Haida, Caterina; Vassilakis, Alexandros; Hatzakis, Angelos

    2008-03-01

    The purpose of our study was to examine the emergence of the Y181C resistance mutation in an NNRTI-naive subject (index patient) at different time points. Phylogenetic trees in protease (PR) and partial reverse transcriptase (RT) regions were inferred by the maximum likelihood (ML) method. The Y181C mutation was detected for the first time when the patient was receiving d4T + ddI + LPV/r; the previous drug combination was 3TC + AZT + IDV. The particular mutation (Y181C) was not present at any time point during the treatment period with 3TC + AZT + IDV. Moreover, there was no evidence of resistance mutations in RT before the initiation of antiretroviral therapy. Phylogenetic analysis including sequences from the index patient and his spouse sampled at different time points, as well as control sequences belonging to the same HIV-1 subtype, revealed that there is no evidence of coinfection or reinfection with Y181C resistance strains, while the virus for both subjects was classified as subtype CRF14_BG. Overall, our findings suggest that the Y181C resistance mutation may be selected, not only by NNRTIs, but also by d4T. This may be of particular significance in developing countries where treatment with Triomune, a fixed combination of d4T, ddI, and nevirapine, is common. The genetic barrier against resistance of this combination may be lower than previously thought.

  11. Platelet count kinetics following interruption of antiretroviral treatment

    DEFF Research Database (Denmark)

    Zetterberg, Eva; Neuhaus, Jacqueline; Baker, Jason V

    2013-01-01

    To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow...

  12. Predicted savings to the UK National Health Service from switching to generic antiretrovirals, 2014–2018

    Directory of Open Access Journals (Sweden)

    Andrew Hill

    2014-11-01

    Full Text Available Introduction: In other disease areas, generic drugs are normally used after patent expiry. Patents on zidovudine, lamivudine, nevirapine and efavirenz have already expired. Patents will expire for abacavir in late 2014, lopinavir/r in 2016, and tenofovir, darunavir and atazanavir in 2017. However, patents on single-tablet regimens do not expire until after 2026. Methods: The number of people taking each antiretroviral in the UK was estimated from 23,655 individuals in the UK CHIC cohort (2012 database. Costs of patented drugs were taken from the British National Formulary database, assuming a 30% discount. Costs of generic antiretrovirals were estimated using an 80% discount from patented prices, or actual costs where available. Two options were analysed: 1 – all patients use single-tablet regimens and patented versions of drugs; prices remain stable over time; 2 – all people switch from patented to generic drugs when available, after patent expiry (dates shown above. Results: There were an estimated 67,000 people taking antiretrovirals in the UK in 2014, estimated to rise by 8% per year until 2018 (in line with previous rises. The most widely used antiretrovirals in the CHIC cohort were tenofovir (TDF (75%, emtricitabine (FTC (69%, efavirenz (EFV (39%, lamivudine (3TC (23%, abacavir (ABC (18%, darunavir (DRV (21% and atazanavir (ATV (16%. The predicted annual UK cost of generic ABC/3TC/EFV (three generic tablets once daily was £1018 per person-year. Costs of patented single-tablet regimens ranged from £5000 to £7500 per person-year. Assuming continued use of patented antiretrovirals in the UK, the predicted total national costs of antiretroviral treatment were predicted to rise from £425 million in 2014 to £459 m in 2015, £495 m in 2016, £536 m in 2017 and £578 m in 2018. With a 100% switch to generics, total predicted costs were £337 m in 2014, £364 m in 2015, £382 m in 2016, £144 m in 2017 and £169 m in 2018. The total

  13. Antiretroviral (HIV-1) activity of azulene derivatives.

    Science.gov (United States)

    Peet, Julia; Selyutina, Anastasia; Bredihhin, Aleksei

    2016-04-15

    The antiretroviral activity of azulene derivatives was detected for the first time. A series of eighteen diversely substituted azulenes was synthesized and tested in vitro using HIV-1 based virus-like particles (VLPs) and infectious HIV-1 virus in U2OS and TZM-bl cell lines. Among the compounds tested, the 2-hydroxyazulenes demonstrated the most significant activity by inhibiting HIV-1 replication with IC50 of 2-10 and 8-20 μM for the VLPs and the infectious virus, respectively. These results indicate that azulene derivatives may be potentially useful candidates for the development of antiretroviral agents.

  14. Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

    Science.gov (United States)

    May, Margaret T.; Vehreschild, Janne; Obel, Niels; Gill, Michael John; Crane, Heidi; Boesecke, Christoph; Samji, Hasina; Grabar, Sophie; Cazanave, Charles; Cavassini, Matthias; Shepherd, Leah; d’Arminio Monforte, Antonella; Smit, Colette; Saag, Michael; Lampe, Fiona; Hernando, Vicky; Montero, Marta; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy; Miro, Jose; Ingle, Suzanne; Sterne, Jonathan A. C.

    2016-01-01

    Objectives To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996–1999 and survived for more than ten years. Methods We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. Results During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years. Conclusions Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes. PMID:27525413

  15. Reduced error signalling in medication-naive children with ADHD

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Allen, Elena A; Eichele, Heike;

    2016-01-01

    and correlated them with reaction times (RT). Additionally, we analyzed post-error adaptations in behaviour and motor component activations. RESULTS: We included 25 children with ADHD and 29 controls in our analysis. Children with ADHD displayed reduced activation to errors in cingulo-opercular regions......BACKGROUND: We examined the blood-oxygen level-dependent (BOLD) activation in brain regions that signal errors and their association with intraindividual behavioural variability and adaptation to errors in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: We acquired...... functional MRI data during a Flanker task in medication-naive children with ADHD and healthy controls aged 8-12 years and analyzed the data using independent component analysis. For components corresponding to performance monitoring networks, we compared activations across groups and conditions...

  16. Left ventricular function in treatment-naive early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Deibjerg, Lone K; Hedemann-Andersen, Agnete;

    2014-01-01

    BACKGROUND: The role of inflammation and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the pathogenesis of cardiovascular disease in early rheumatoid arthritis (RA) remains unclear. Previous studies have suggested that both disease activity and disease duration are associated...... with atherosclerosis and a higher mortality rate caused primarily by coronary artery disease. OBJECTIVE: We investigated how disease activity, anti-CCP status and coronary calcium score in treatment-naive early RA impacts left ventricular (LV) systolic function. METHODS: Fifty-tree patients (30 women) with mean age 58...... by computed tomography by calculating the Agaston score. One experienced senior rheumatologist and one experienced cardiologist performed all the clinical assessments as well as all the transthoracic echocardiography (TTE) and coronary CT analysis. RESULTS: Disease activity scores before treatment at baseline...

  17. Combining Naive Bayes and Decision Tree for Adaptive Intrusion Detection

    CERN Document Server

    Farid, Dewan Md; Rahman, Mohammad Zahidur; 10.5121/ijnsa.2010.2202

    2010-01-01

    In this paper, a new learning algorithm for adaptive network intrusion detection using naive Bayesian classifier and decision tree is presented, which performs balance detections and keeps false positives at acceptable level for different types of network attacks, and eliminates redundant attributes as well as contradictory examples from training data that make the detection model complex. The proposed algorithm also addresses some difficulties of data mining such as handling continuous attribute, dealing with missing attribute values, and reducing noise in training data. Due to the large volumes of security audit data as well as the complex and dynamic properties of intrusion behaviours, several data miningbased intrusion detection techniques have been applied to network-based traffic data and host-based data in the last decades. However, there remain various issues needed to be examined towards current intrusion detection systems (IDS). We tested the performance of our proposed algorithm with existing learn...

  18. Naive Bayes-Guided Bat Algorithm for Feature Selection

    Directory of Open Access Journals (Sweden)

    Ahmed Majid Taha

    2013-01-01

    Full Text Available When the amount of data and information is said to double in every 20 months or so, feature selection has become highly important and beneficial. Further improvements in feature selection will positively affect a wide array of applications in fields such as pattern recognition, machine learning, or signal processing. Bio-inspired method called Bat Algorithm hybridized with a Naive Bayes classifier has been presented in this work. The performance of the proposed feature selection algorithm was investigated using twelve benchmark datasets from different domains and was compared to three other well-known feature selection algorithms. Discussion focused on four perspectives: number of features, classification accuracy, stability, and feature generalization. The results showed that BANB significantly outperformed other algorithms in selecting lower number of features, hence removing irrelevant, redundant, or noisy features while maintaining the classification accuracy. BANB is also proven to be more stable than other methods and is capable of producing more general feature subsets.

  19. The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil.

    Science.gov (United States)

    Lopes, Carmen Andréa F; Soares, Marcelo A; Falci, Diego R; Sprinz, Eduardo

    2015-01-01

    HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1%) and K130N (40.6%). Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%). There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option.

  20. The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil

    Directory of Open Access Journals (Sweden)

    Carmen Andréa F. Lopes

    2015-01-01

    Full Text Available HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1% and K130N (40.6%. Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%. There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option.

  1. Soluble urokinase receptor levels in plasma during 5 years of highly active antiretroviral therapy in HIV-1-infected patients

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Katzenstein, Terese L; Piironen, Timo;

    2004-01-01

    High blood levels of the soluble urokinase receptor (suPAR) strongly predict increased mortality in human immunodeficiency virus-1 (HIV-1)-infected patients. This study investigated the plasma concentration of suPAR in 29 treatment-naive HIV-1-infected patients during 5 years treatment with highly...... active antiretroviral therapy (HAART). Plasma suPAR decreased after introducing HAART, most pronounced during the first treatment year. The change in plasma suPAR was independent of changes in viral replication and CD4+ cells but it was strongly correlated with plasma levels of the soluble TNF receptor...... is linked to inflammation in untreated as well as HAART-treated HIV-1-infected patients....

  2. Maraviroc 150 mg daily plus lopinavir/ritonavir, a nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimen for HIV-infected naive patients: 48-week final results of VEMAN study.

    Science.gov (United States)

    Nozza, S; Galli, L; Antinori, A; Chiappetta, S; Mazzotta, F; Zaccarelli, M; Ottou, S; De Battista, D; Pogliaghi, M; Di Pietro, M; Malnati, M; Ripa, M; Bonora, S; Lazzarin, A

    2015-05-01

    Non-conventional strategies with nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimens in antiretroviral naive human immunodeficiency virus (HIV) -infected patients have been explored in clinical trials. A prospective, open-label, randomized (1:1), multicentre, proof-of-concept trial (VEMAN study, EUDRACT number 2008-006287-11) was conducted assigning HIV-infected naive patients to once-daily maraviroc plus lopinavir/ritonavir (MVC group) or to tenofovir/emtricitabine plus lopinavir/ritonavir (TDF/FTC group). Clinical and laboratory data were collected at baseline, and after 4, 12, 24, 36 and 48 weeks with the objective to evaluate the 48-week virological and immunological efficacy. HIV-1 DNA load and CD4(+) T-cell subsets were analysed on frozen peripheral blood mononuclear cells collected at baseline, 4 and 48 weeks to explore the trend in HIV reservoirs. Fifty patients were randomized and included in the analysis. During follow up, HIV-1 RNA decreased similarly in both groups and, at week 48, all patients in the MVC group and 22/24 (96%) in the TDF/FTC group had < 50 copies/ml of HIV-1 RNA. CD4(+) trend during follow up was higher in maraviroc-treated patients (MVC group: 286 (183-343) versus TDF/FTC group: 199 (125-285); Mann-Whitney U-test: p 0.033). A significant 48-week increase of CCR5(+) CD4(+) T cells and CD4(+) effector memory cells was observed among maraviroc-treated patients (Wilcoxon signed rank test: p 0.016 and p 0.007, respectively). No significant variations were found in naive and central memory CD4(+) T cells. Among naive patients with an R5 virus, treatment with maraviroc and lopinavir/ritonavir was shown to provide a virological response compared to a triple therapy and a greater immunological benefit.

  3. A review of 20 years of naive tests of significance for high-dimensional mean vectors and covariance matrices

    Science.gov (United States)

    Hu, Jiang; Bai, ZhiDong

    2016-12-01

    In this paper, we will introduce the so called naive tests and give a brief review on the newly development. Naive testing methods are easy to understand and performs robust especially when the dimension is large. In this paper, we mainly focus on reviewing some naive testing methods for the mean vectors and covariance matrices of high dimensional populations and believe this naive test idea can be wildly used in many other testing problems.

  4. HIV-1 Genetic Diversity and Drug Resistance Mutations Among Treatment-Naive Adult Patients in Suriname.

    Science.gov (United States)

    Abdoel Wahid, Firoz; Sno, Rachel; Darcissac, Edith; Lavergne, Anne; Adhin, Malti R; Lacoste, Vincent

    2016-12-01

    The molecular epidemiologic profile of HIV-1 in Suriname was determined through protease (PR) and reverse transcriptase (RT) sequences obtained from HIV-1 strains collected from 100 drug-naive HIV-1-infected persons. Subtype determination revealed that most viruses were of subtype B (94.9%) in both PR and RT genomic regions, followed by B/D recombinants (5.1%). Analysis of drug resistance mutations showed only one transmitted dug resistance mutation (TDRM) (V75M) in a single strain. The genetic data obtained can serve as a baseline for Suriname to monitor emerging mutations. This study reveals that the HIV-1 epidemic in Suriname is still characterized by a low TDRM rate (1%) and a low level of subtype diversity. However, both genes display a high genetic polymorphism. This high polymorphism may ultimately lead to drug resistance. Continuous monitoring of the baseline resistance is therefore a prerequisite to safeguard effective long-term treatment for people living with HIV-1 in Suriname.

  5. Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

    DEFF Research Database (Denmark)

    Borges, Álvaro H; Neuhaus, Jacqueline; Babiker, Abdel G;

    2016-01-01

    BACKGROUND:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts...... and human immunodeficiency virus (HIV) RNA between the study arms. METHODS:  Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline...... covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART. RESULTS:  There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23...

  6. File list: InP.Bld.05.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Naive_T_cells hg19 Input control Blood Naive T cells SRX1425815,SR...X1425816,SRX1425814 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.05.AllAg.Naive_T_cells.bed ...

  7. File list: InP.Bld.50.AllAg.Naive_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.Naive_T_cells hg19 Input control Blood Naive T cells SRX1425815,SR...X1425816,SRX1425814 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.50.AllAg.Naive_T_cells.bed ...

  8. T-CELL RESPONSE OF ADVANCED AIDS PATIENTS AFTER HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

    Institute of Scientific and Technical Information of China (English)

    Ai-xia Wang; Tai-sheng Li; Yun-zhen Cao; Yang Han; Zhi-feng Qiu; Jing Xie

    2005-01-01

    Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy (HAART).Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients were selected to participate in this opened and randomised study, we purposely chose those with CD4+ T cell counts < 100/mm3. All of them had one or two opportunistic infections and none had been treated with anti-HIV drugs. All patients were tested with CD4+(naive CD4+ T cell defined by CD45RA+ and CD62L+, memory CD4+ T cell defined by CD45RA-), CD8+ T cell,plasma HIV viral load, and clinical manifestations on before, during, and after HAART (5 different regimes) on 1, 3, 6, 9,and 12 months.Results Before HAART mean CD4+ T cell counts were 32 ± 31 (range 2-91)/mm3, and plasma HIV viral load were 5.07±0.85(range 2.04-5.70) log copies/mL. In 1 month's time patients treated with HAART had mean CD4+ and CD8T cell counts increasing rapidly. After 1 month the increasing speed turned to slow down, but HIV viral load decreased predominantly within the first 3 months. The major part of increasing CD4+ T cells were memory CD4+ T cells, as for naive CD4+ T cells increasing low and slow. Clinical symptoms and signs improved, and opportunistic infections reduced. The quality of life will be far much better than before. Each patient was followed for 12 months, and had finished 12 months' HAART.Conclusion This is the first report in China that late stage Chinese AIDS patients after HAART could have their immune reconstitution. The regular pattern is similar to what had been reported in Western countries and also in China. So it is worth to treat late stage Chinese AIDS patients with HAART.

  9. Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings

    DEFF Research Database (Denmark)

    Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette;

    2002-01-01

    In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size...... and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR...... count (r = 0.083, p = 0.706), naive CD4 count (r = 0.067, p = 0.762), CD4 + TREC frequency (r = 0.028, p = 0.900) and CD4 + TCR repertoire (r = -0.057, p = 0.828). These findings show that CT remains superior for assessing thymic size in adults and is preferable to ultrasound when evaluating...

  10. Guidelines for antiretroviral therapy in adults

    Directory of Open Access Journals (Sweden)

    G Meintjes

    2012-09-01

    Full Text Available These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in January 2008. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART in Southern Africa has continued to grow. Cohort studies from the region show excellent clinical outcomes; however, ART is still being started late (in advanced disease, resulting in relatively high early mortality rates. New data on antiretroviral (ARV tolerability in the region and several new ARV drugs have become available. Although currently few in number, some patients in the region are failing protease inhibitor (PI-based second-line regimens. To address this, guidelines on third-line (or ‘salvage’ therapy have been expanded.

  11. Drug resistance and antiretroviral drug development

    OpenAIRE

    Shafer, Robert W.; Jonathan M Schapiro

    2005-01-01

    As more drugs for treating HIV have become available, drug resistance profiles within antiretroviral drug classes have become increasingly important for researchers developing new drugs and for clinicians integrating new drugs into their clinical practice. In vitro passage experiments and comprehensive phenotypic susceptibility testing are used for the pre-clinical evaluation of drug resistance. Clinical studies are required, however, to delineate the full spectrum of mutations responsible fo...

  12. Interaction of antiretroviral medications with finasteride

    OpenAIRE

    Ward, D.

    2012-01-01

    Antiretroviral medications are known inhibitors and inducers of cytochrome p450 enzymes and can affect levels of non-HIV medications. Finasteride 1 mg (Propecia), which prevents the conversion of testosterone (T) to dihydrotestosterone (DHT) is commonly prescribed for prevention of hair loss. This medication is a substrate of p450 3A4. Its efficacy may therefore be affected by HIV medications which induce or inhibit this enzyme. Levels of DHT to prevent hair loss are not well established, but...

  13. Local Naive Bayes Nearest Neighbor for Image Classification

    CERN Document Server

    McCann, Sancho

    2011-01-01

    We present Local Naive Bayes Nearest Neighbor, an improvement to the NBNN image classification algorithm that increases classification accuracy and improves its ability to scale to large numbers of object classes. The key observation is that only the classes represented in the local neighborhood of a descriptor contribute significantly and reliably to their posterior probability estimates. Instead of maintaining a separate search structure for each class, we merge all of the reference data together into one search structure, allowing quick identification of a descriptor's local neighborhood. We show an increase in classification accuracy when we ignore adjustments to the more distant classes and show that the run time grows with the log of the number of classes rather than linearly in the number of classes as did the original. This gives a 100 times speed-up over the original method on the Caltech 256 dataset. We also provide the first head-to-head comparison of NBNN against spatial pyramid methods using a co...

  14. Combining Naive Bayes and Decision Tree for Adaptive Intrusion Detection

    Directory of Open Access Journals (Sweden)

    Dewan Md. Farid

    2010-04-01

    Full Text Available In this paper, a new learning algorithm for adaptive network intrusion detection using naive Bayesian classifier and decision tree is presented, which performs balance detections and keeps false positives at acceptable level for different types of network attacks, and eliminates redundant attributes as well as contradictory examples from training data that make the detection model complex. The proposedalgorithm also addresses some difficulties of data mining such as handling continuous attribute, dealing with missing attribute values, and reducing noise in training data. Due to the large volumes of security audit data as well as the complex and dynamic properties of intrusion behaviours, several data miningbased intrusion detection techniques have been applied to network-based traffic data and host-based data in the last decades. However, there remain various issues needed to be examined towards current intrusion detection systems (IDS. We tested the performance of our proposed algorithm with existing learning algorithms by employing on the KDD99 benchmark intrusion detection dataset. The experimental results prove that the proposed algorithm achieved high detection rates (DR andsignificant reduce false positives (FP for different types of network intrusions using limited computational resources

  15. Naive Dimensional Analysis for Three-Body Forces Without Pions

    CERN Document Server

    Griesshammer, H W

    2005-01-01

    For systems of three identical particles in which short-range forces produce shallow two-particle bound states, and in particular for the ``pion-less'' Effective Field Theory of Nuclear Physics, I extend and systematise the power-counting of three-body forces to all partial-waves and orders, including external currents. With low-energy observables independent of the details of short-distance dynamics, the typical strength of a three-body force is determined from the superficial degree of divergence of the three-body diagrams which contain only two-body forces. This na\\"ive dimensional analysis must be amended as the asymptotic solution to the leading-order Faddeev equation depends for large off-shell momenta crucially on the partial wave and spin-combination of the system. It is shown by analytic construction to be weaker in most channels with angular momentum smaller than 3 than expected. This demotes many three-nucleon forces to high orders. Observables like the quartet-S-scattering length are less sensitiv...

  16. Executed Movement Using EEG Signals through a Naive Bayes Classifier

    Directory of Open Access Journals (Sweden)

    Juliano Machado

    2014-11-01

    Full Text Available Recent years have witnessed a rapid development of brain-computer interface (BCI technology. An independent BCI is a communication system for controlling a device by human intension, e.g., a computer, a wheelchair or a neuroprosthes is, not depending on the brain’s normal output pathways of peripheral nerves and muscles, but on detectable signals that represent responsive or intentional brain activities. This paper presents a comparative study of the usage of the linear discriminant analysis (LDA and the naive Bayes (NB classifiers on describing both right- and left-hand movement through electroencephalographic signal (EEG acquisition. For the analysis, we considered the following input features: the energy of the segments of a band pass-filtered signal with the frequency band in sensorimotor rhythms and the components of the spectral energy obtained through the Welch method. We also used the common spatial pattern (CSP filter, so as to increase the discriminatory activity among movement classes. By using the database generated by this experiment, we obtained hit rates up to 70%. The results are compatible with previous studies.

  17. Similar Words Identification Using Naive and TF-IDF Method

    Directory of Open Access Journals (Sweden)

    Divya K.S.

    2014-10-01

    Full Text Available Requirement satisfaction is one of the most important factors to success of software. All the requirements that are specified by the customer should be satisfied in every phase of the development of the software. Satisfaction assessment is the determination of whether each component of the requirement has been addressed in the design document. The objective of this paper is to implement two methods to identify the satisfied requirements in the design document. To identify the satisfied requirements, similar words in both of the documents are determined. The methods such as Naive satisfaction assessment and TF-IDF satisfaction assessment are performed to determine the similar words that are present in the requirements document and design documents. The two methods are evaluated on the basis of the precision and recall value. To perform the stemming, the Porter’s stemming algorithm is used. The satisfaction assessment methods would determine the similarity in the requirement and design documents. The final result would give a accurate picture of the requirement satisfaction so that the defects can be determined at the early stage of software development. Since the defects determines at the early stage, the cost would be low to correct the defects.

  18. Dosing antiretroviral medication when crossing time zones: a review.

    Science.gov (United States)

    Lewis, Joseph M; Volny-Anne, Alain; Waitt, Catriona; Boffito, Marta; Khoo, Saye

    2016-01-01

    International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones.

  19. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study

    OpenAIRE

    Ekouevi, Didier K; Coffie, Patrick A.; Eugene Messou; Adrien Sawadogo; Eholie, Serge P.; Djimon Marcel Zannou; Carin Ahouada; Jocelyn Akakpo; Christelle Ahomadegbé; Jules Bashi; Alice Gougounon-Houéto; Angèle Azon-Kouanou; Fabien Houngbé; Sikiratou Koumakpaï; Florence Alihonou

    2013-01-01

    Background HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). Methods We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART)...

  20. Antiretroviral salvage therapy for multiclass drug-resistant HIV-1-infected patients: from clinical trials to daily clinical practice.

    Science.gov (United States)

    Imaz, Arkaitz; Falcó, Vicenç; Ribera, Esteban

    2011-01-01

    Drug resistance is one of the key problems in the management of long-term HIV-1-infected patients. Due to cross-resistance patterns within classes, broad resistance to the three original antiretroviral classes can develop in some patients, mainly those with extensive antiretroviral treatment experience and multiple treatment failures. Triple-class-resistant HIV-1 infection has been associated with a higher risk of clinical progression and death. Additionally, it increases the probability of transmission of multidrug-resistant HIV-1 strains. Over the last years, the availability of new antiretroviral agents against novel targets (integrase inhibitors and CCR5 antagonists), and new drugs within old classes (nonnucleoside reverse transcriptase inhibitors and protease inhibitors) has opened a range of new therapeutic options for patients with multiclass drug-resistant HIV-1 infection and scarce therapeutic options with previous drugs. In randomized clinical trials, each of these new drugs has shown exceptional efficacy results, especially in patients who received other fully active drugs in the regimen. Indeed, in nonrandomized trials and observational studies, unprecedented rates of virologic suppression similar to those obtained in naive patients have been achieved when three of the currently available new drugs were combined, even in heavily experienced patients who had no viable salvage options with the previous classes. Thus, the goal of suppression and maintenance (plasma HIV-1 RNA infection. Treatment failure can still occur, however, and the management of patients with multidrug-resistant HIV-1 infection remains a challenge. Clinicians are encouraged to optimize use of the new drugs to obtain better control of HIV infection while avoiding emergence of new resistance-associated mutations. The aim of this article is to summarize current knowledge on the management of salvage therapy for patients with multidrug-resistant HIV-1 infection by analyzing the evidence

  1. Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment

    Directory of Open Access Journals (Sweden)

    Sinha Sanjeev

    2012-07-01

    Full Text Available Abstract Background For antiretroviral therapy (ART naive human immunodeficiency virus (HIV infected adults suffering from tuberculosis (TB, there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART after starting antituberculosis treatment (ATT, in order to minimize mortality, HIV disease progression, and adverse events. Methods In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART and 62 after 8-12 weeks (delayed ART of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045. Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05. Rates of adverse events were similar. Interpretation Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Trial registration CTRI/2011/12/002260

  2. Improving Naive Bayes with Online Feature Selection for Quick Adaptation to Evolving Feature Usefulness

    Energy Technology Data Exchange (ETDEWEB)

    Pon, R K; Cardenas, A F; Buttler, D J

    2007-09-19

    The definition of what makes an article interesting varies from user to user and continually evolves even for a single user. As a result, for news recommendation systems, useless document features can not be determined a priori and all features are usually considered for interestingness classification. Consequently, the presence of currently useless features degrades classification performance [1], particularly over the initial set of news articles being classified. The initial set of document is critical for a user when considering which particular news recommendation system to adopt. To address these problems, we introduce an improved version of the naive Bayes classifier with online feature selection. We use correlation to determine the utility of each feature and take advantage of the conditional independence assumption used by naive Bayes for online feature selection and classification. The augmented naive Bayes classifier performs 28% better than the traditional naive Bayes classifier in recommending news articles from the Yahoo! RSS feeds.

  3. Subtrochanteric Fractures in Bisphosphonate-Naive Patients: Results from the HORIZON-Recurrent Fracture Trial

    OpenAIRE

    2011-01-01

    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained incident subtrochanteric fractures with those sustaining other hip fractures. Subjects were bisphosphonate-naive or had a bisphosphonate washout period of 6–24 months and subsequently received an annu...

  4. Naive Juveniles Are More Likely to Become Breeders after Witnessing Predator Mobbing.

    Science.gov (United States)

    Griesser, Michael; Suzuki, Toshitaka N

    2017-01-01

    Responding appropriately during the first predatory attack in life is often critical for survival. In many social species, naive juveniles acquire this skill from conspecifics, but its fitness consequences remain virtually unknown. Here we experimentally demonstrate how naive juvenile Siberian jays (Perisoreus infaustus) derive a long-term fitness benefit from witnessing knowledgeable adults mobbing their principal predator, the goshawk (Accipiter gentilis). Siberian jays live in family groups of two to six individuals that also can include unrelated nonbreeders. Field observations showed that Siberian jays encounter predators only rarely, and, indeed, naive juveniles do not respond to predator models when on their own but do when observing other individuals mobbing them. Predator exposure experiments demonstrated that naive juveniles had a substantially higher first-winter survival after observing knowledgeable group members mobbing a goshawk model, increasing their likelihood of acquiring a breeding position later in life. Previous research showed that naive individuals may learn from others how to respond to predators, care for offspring, or choose mates, generally assuming that social learning has long-term fitness consequences without empirical evidence. Our results demonstrate a long-term fitness benefit of vertical social learning for naive individuals in the wild, emphasizing its evolutionary importance in animals, including humans.

  5. Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation.

    Science.gov (United States)

    Sahakyan, Anna; Kim, Rachel; Chronis, Constantinos; Sabri, Shan; Bonora, Giancarlo; Theunissen, Thorold W; Kuoy, Edward; Langerman, Justin; Clark, Amander T; Jaenisch, Rudolf; Plath, Kathrin

    2017-01-05

    Naive human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X chromosome state has remained unresolved. Here, we show that the inactive X chromosome (Xi) of primed hESCs was reactivated in naive culture conditions. Like cells of the blastocyst, the resulting naive cells contained two active X chromosomes with XIST expression and chromosome-wide transcriptional dampening and initiated XIST-mediated X inactivation upon differentiation. Both establishment of and exit from the naive state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X chromosome dosage compensation processes in early human development: X dampening and X inactivation. However, remaining differences between naive hESCs and embryonic cells related to mono-allelic XIST expression and non-random X inactivation highlight the need for further culture improvement. As the naive state resets Xi abnormalities seen in primed hESCs, it may provide cells better suited for downstream applications.

  6. Nevirapine-Based Antiretroviral Therapy Impacts Artesunate and Dihydroartemisinin Disposition in HIV-Infected Nigerian Adults

    Directory of Open Access Journals (Sweden)

    Fatai A. Fehintola

    2012-01-01

    Full Text Available Background. Nevirapine- (NVP- based antiretroviral therapy (ART and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics. Methods. We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n=10 and ART-naive controls (n=11. Artesunate-amodiaquine 200/600 mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis. Results. Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P=0.03, resulting in a 45% increase in the AUC0-96 (105 versus 69 ug∗hr/L; P=0.02. The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P=0.004, but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC0-96=5.6 versuss 8.5 in NVP and control groups, respectively, P=0.008. Conclusion. Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.

  7. The role of formulation on the pharmacokinetics of antiretroviral drugs

    NARCIS (Netherlands)

    Bastiaans, Diane E T; Cressey, Tim R; Vromans, Herman; Burger, David M

    2014-01-01

    INTRODUCTION: A multitude of antiretroviral drug formulations are now available for HIV-infected adults and children. These formulations include individual and co-formulated drugs, many of which are also supplied in generic versions. Many antiretroviral drugs have a low aqueous solubility and poor b

  8. Interaction of antiretroviral medications with finasteride

    Directory of Open Access Journals (Sweden)

    D Ward

    2012-11-01

    Full Text Available Antiretroviral medications are known inhibitors and inducers of cytochrome p450 enzymes and can affect levels of non-HIV medications. Finasteride 1 mg (Propecia, which prevents the conversion of testosterone (T to dihydrotestosterone (DHT is commonly prescribed for prevention of hair loss. This medication is a substrate of p450 3A4. Its efficacy may therefore be affected by HIV medications which induce or inhibit this enzyme. Levels of DHT to prevent hair loss are not well established, but likely need to be<15–20 ng/dl, or a DHT/T ratio of<0.02. Observational analysis in a private practice, measuring DHT and T levels in patients on finasteride and various antiretrovirals 21 patients were identified. 7 patients were taking protease inhibitors and had DHT levels<12 ng/dL; DHT/T<0.20. Three of these patients decreased their finasteride dose to 1 mg every-other-day and still have DHT <10. 8 patients were taking potent p450 inducers (efavirenz or etravirine and had DHT levels between >20; DHT/T>0.025. Two of these patients increased the dose of finasteride to 2 mg/day and subsequently decreased DHT to 14 and 17. Two additional patients on efavirenz, however, had DHT levels of<15 without dose adjustment. Four patients taking nevirapine, a less potent inducer of p450 had DHT levels of<15, as did one patient on raltegravir, which does not affect CYP450. Antiretrovirals that affect CYP 3A4 may interact with finasteride. While it is unlikely that this interaction is dangerous, it may affect its efficacy of the finasteride. Evaluation of DHT/T levels, and/or dose adjustment of finasteride may be appropriate in men being treated for HIV.

  9. Cytomegalovirus retinitis after initiation of antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Zahra Ahmadinejad

    2013-10-01

    Full Text Available Patients with human immunodeficiency virus (HIV infection receiving antiretroviral therapy (ART, despite a reduced viral load and improved immune responses, may experience clinical deterioration. This so called "immune reconstitution inflammatory syndrome (IRIS" is caused by inflammatory response to both intact subclinical pathogens and residual antigens. Cytomegalovirus retinitis is common in HIV-infected patients on ART with a cluster differentiation 4 (CD4+ counts less than 50 cells/mm3. We reported a patient with blurred vision while receiving ART. She had an unmasking classic CMV retinitis after ART.

  10. Helicobacter pylori infection: Is sequential therapy superior to standard triple therapy? A single-centre Italian study in treatment-naive and non-treatment-naive patients

    Science.gov (United States)

    Urgesi, R; Pelecca, G; Cianci, R; Masini, A; Zampaletta, C; Riccioni, ME; Faggiani, R

    2011-01-01

    BACKGROUND: Clarithromycin resistance has decreased the eradication rates of Helicobacter pylori. AIMS: To determine whether a 10-day course of sequential therapy (ST) is more effective at eradicating H pylori infection than triple therapy (TT) in the first or second line, and to assess side effects and compliance with therapy. METHODS: One hundred sixty treatment-naive and 40 non-treatment-naive patients who were positive for H pylori infection by 13C-urea breath test or endoscopy were enrolled. Eighty of 160 patients underwent TT, while 80 of 160 underwent ST with omeprazole (20 mg) plus amoxicillin (1 g) twice/day for five days, followed by omeprazole (20 mg) with tinidazole (500 mg) twice/day and clarithromycin (500 mg) twice/day for five consecutive days. H pylori eradication was evaluated by 13C-urea breath test no sooner than four weeks after the end of treatment. RESULTS: Eradication was achieved in 59 of 80 treatment-naive patients treated with TT (74%), in 74 of 80 patients treated with ST (93%), and in 38 of 40 non-treatment-naive patients (95%). Eradication rates in treatment-naive patients with ST were statistically significantly higher than TT (92.5% versus 73.7%; P=0.0015; OR 4.39 [95% CI 1.66 to 11.58]). Mild adverse effects were reported for both regimens. CONCLUSIONS: ST appears to be a well-tolerated, promising therapy; however, randomized controlled trials with larger and more diverse sample populations are needed before it can be recommended as a first-line treatment. PMID:21766091

  11. The other genome: a systematic review of studies of mitochondrial DNA haplogroups and outcomes of HIV infection and antiretroviral therapy.

    Science.gov (United States)

    Hart, Anna B; Samuels, David C; Hulgan, Todd

    2013-01-01

    Mitochondrial toxicity is implicated in some treatment-limiting antiretroviral therapy complications, and reports of mitochondrial dysfunction in untreated HIV infection suggest antiretroviral therapy independent effects of HIV. Several studies have explored associations between mtDNA haplogroups (patterns of mtDNA polymorphisms) and outcomes of HIV infection and/or antiretroviral therapy, but findings have been inconsistent. We systematically reviewed published studies examining mtDNA haplogroups in HIV-infected persons to summarize reported outcome associations, and to highlight potential future research directions. We identified 21 articles published from 2005-2013. Multiple different phenotypes were studied; most were antiretroviral therapy associated metabolic outcomes (e.g. lipodystrophy, insulin resistance, and dyslipidemia). Haplogroup H was associated with the most outcomes, including AIDS progression, CD4 T-cell recovery, cirrhosis (in hepatitis C coinfection), and metabolic outcomes. This review is the first to focus on the emerging area of mtDNA haplogroups in HIV, and summarizes the published literature on associations between mtDNA haplogroups and clinical outcomes in populations of European and African descent. Several reported associations require replication and ideally biological verification before definitive conclusions can be drawn, but research in this area has the potential to explain outcome disparities and impact clinical management of patients.

  12. Differential T cell receptor-mediated signaling in naive and memory CD4 T cells.

    Science.gov (United States)

    Farber, D L; Acuto, O; Bottomly, K

    1997-08-01

    Naive and memory CD4 T cells differ in cell surface phenotype, function, activation requirements, and modes of regulation. To investigate the molecular bases for the dichotomies between naive and memory CD4 T cells and to understand how the T cell receptor (TCR) directs diverse functional outcomes, we investigated proximal signaling events triggered through the TCR/CD3 complex in naive and memory CD4 T cell subsets isolated on the basis of CD45 isoform expression. Naive CD4 T cells signal through TCR/CD3 similar to unseparated CD4 T cells, producing multiple tyrosine-phosphorylated protein species overall and phosphorylating the T cell-specific ZAP-70 tyrosine kinase which is recruited to the CD3zeta subunit of the TCR. Memory CD4 T cells, however, exhibit a unique pattern of signaling through TCR/CD3. Following stimulation through TCR/CD3, memory CD4 T cells produce fewer species of tyrosine-phosphorylated substrates and fail to phosphorylate ZAP-70, yet unphosphorylated ZAP-70 can associate with the TCR/CD3 complex. Moreover, a 26/28-kDa phosphorylated doublet is associated with CD3zeta in resting and activated memory but not in naive CD4 T cells. Despite these differences in the phosphorylation of ZAP-70 and CD3-associated proteins, the ZAP-70-related kinase, p72syk, exhibits similar phosphorylation in naive and memory T cell subsets, suggesting that this kinase could function in place of ZAP-70 in memory CD4 T cells. These results indicate that proximal signals are differentially coupled to the TCR in naive versus memory CD4 T cells, potentially leading to distinct downstream signaling events and ultimately to the diverse functions elicited by these two CD4 T cell subsets.

  13. Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals

    Science.gov (United States)

    Winand, Raf; Theys, Kristof; Eusébio, Mónica; Aerts, Jan; Camacho, Ricardo J.; Gomes, Perpetua; Suchard, Marc A.; Vandamme, Anne-Mieke; Abecasis, Ana B.

    2015-01-01

    Objectives: Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs. Design: This is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients. Methods: The prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility. Results: Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers – above (PRO: D30N, N88D/S, L90 M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads. Conclusion: The significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with

  14. Genomic and transcriptomic plasticity in treatment-naive ovarian cancer

    NARCIS (Netherlands)

    Hoogstraat, Marlous; de Pagter, Mirjam S; Cirkel, Geert A; van Roosmalen, Markus J; Harkins, Timothy T; Duran, Karen; Kreeftmeijer, Jennifer; Renkens, Ivo; Witteveen, Petronella O; Lee, Clarence C; Nijman, Isaac J; Guy, Tanisha; van 't Slot, Ruben; Jonges, Trudy N; Lolkema, Martijn P; Koudijs, Marco J; Zweemer, Ronald P; Voest, Emile E; Cuppen, Edwin; Kloosterman, Wigard P

    2014-01-01

    Intra-tumor heterogeneity is a hallmark of many cancers and may lead to therapy resistance or interfere with personalized treatment strategies. Here, we combined topographic mapping of somatic breakpoints and transcriptional profiling to probe intra-tumor heterogeneity of treatment-naïve stage IIIC/

  15. Pertussis toxin activates adult and neonatal naive human CD4+ T lymphocytes.

    Science.gov (United States)

    Tonon, Sandrine; Badran, Bassam; Benghiat, Fleur Samantha; Goriely, Stanislas; Flamand, Véronique; Willard-Gallo, Karen; Willems, Fabienne; Goldman, Michel; De Wit, Dominique

    2006-07-01

    Pertussis toxin (PTX) is known to be mitogenic for T lymphocytes, but its direct action on naive human T cells has not been specified. Herein, we show that PTX induces the proliferation of purified adult CD45RA(+)CD4(+) T cells independently of its ADP-ribosyltransferase activity. PTX directly induces TNF-alpha and IL-2 mRNA expression, modulates the level of several cell surface receptors and induces Forkhead box p3 (Foxp3) protein accumulation in naive CD4(+) T cells. Addition of autologous dendritic cells was found to be required for the production of high levels of IFN-gamma by PTX-stimulated naive T cells. These effects of PTX occurred in conjunction with activation of NF-kappaB and NFAT transcription factors. Overall, responses of neonatal CD4(+) T cells to PTX were similar to those of adult CD45RA(+)CD4(+) naive T cells except for their blunted CD40 ligand up-regulation. We suggest that the adjuvant properties of PTX during primary cell-mediated immune responses involve a direct action on naive T lymphocytes in addition to activation of antigen-presenting cells.

  16. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis

    Science.gov (United States)

    Wojciechowski, Sara; Tripathi, Pulak; Bourdeau, Tristan; Acero, Luis; Grimes, H. Leighton; Katz, Jonathan D.; Finkelman, Fred D.; Hildeman, David A.

    2007-01-01

    We examined the role of the antiapoptotic molecule Bcl-2 in combating the proapoptotic molecule Bim in control of naive and memory T cell homeostasis using Bcl-2−/− mice that were additionally deficient in one or both alleles of Bim. Naive T cells were significantly decreased in Bim+/−Bcl-2−/− mice, but were largely restored in Bim−/−Bcl-2−/− mice. Similarly, a synthetic Bcl-2 inhibitor killed wild-type, but not Bim−/−, T cells. Further, T cells from Bim+/−Bcl-2−/− mice died rapidly ex vivo and were refractory to cytokine-driven survival in vitro. In vivo, naive CD8+ T cells required Bcl-2 to combat Bim to maintain peripheral survival, whereas naive CD4+ T cells did not. In contrast, Bim+/−Bcl-2−/− mice generated relatively normal numbers of memory T cells after lymphocytic choriomeningitis virus infection. Accumulation of memory T cells in Bim+/−Bcl-2−/− mice was likely caused by their increased proliferative renewal because of the lymphopenic environment of the mice. Collectively, these data demonstrate a critical role for a balance between Bim and Bcl-2 in controlling homeostasis of naive and memory T cells. PMID:17591857

  17. Posaconazole: A Review of Drug Interactions with HIV Antiretroviral Agents

    Directory of Open Access Journals (Sweden)

    Mara Poulakos

    2014-03-01

    Full Text Available The purpose of this review is to examine the literature for reports of clinically significant interactions noted amongst HIV antiretroviral medications when coadministered with posaconazole. A literature search was conducted to identify studies addressing drug interactions between posaconazole and HIV antiretroviral medications. Two pharmacokinetic studies and three clinical trials involving the administration of posaconazole to HIV-infected patients were identified. The pharmacokinetic studies involved concomitant administration of either a protease inhibitor (PI or non-nucleoside reverse transcriptase inhibitor (NNRTI. Both studies showed alterations in systemic concentrations of either posaconazole or the HIV antiretroviral when administered together. Of the three clinical trials, all patients were on HIV antiretrovirals. However, their potential interaction with posaconazole was not explored. To date, there is no published literature regarding the interaction between maraviroc or elvitegravir and posaconazole. Dose adjustments for each are recommended when coadministered with strong CYP 3A4 inhibitors or inducers. Currently available literature points to the potential for clinically significant drug interactions when posaconazole is coadministered with HIV antiretrovirals, specifically NNRTIs and PIs. More studies are needed involving a wider range of HIV antiretrovirals to determine the significance of the interaction. Clinicians should be aware of this potentially significant interaction and avoid concomitant administration when possible. When available, consideration should be given to therapeutic drug monitoring of antiretroviral serum concentrations in select patients.

  18. Experiencing antiretroviral adherence: helping healthcare staff better understand adherence to paediatric antiretrovirals

    Directory of Open Access Journals (Sweden)

    Phelps Benjamin R

    2010-12-01

    Full Text Available Abstract Background Lack of adherence to antiretroviral medications is one of the key challenges for paediatric HIV care and treatment programmes. There are few hands-on opportunities for healthcare workers to gain awareness of the psychosocial and logistic challenges that caregivers face when administering daily antiretroviral therapy to children. This article describes an educational activity that allows healthcare workers to simulate this caregiver role. Methods Paediatric formulations of several antiretroviral medications were dispensed to a convenience sample of staff at the Baylor College of Medicine-Bristol-Myers Squibb Children's Clinical Center of Excellence in Mbabane, Swaziland. The amounts of the medications remaining were collected and measured one week later. Adherence rates were calculated. Following the exercise, a brief questionnaire was administered to all staff participants. Results The 27 clinic staff involved in the exercise had varying and low adherence rates over the week during which the exercise was conducted. Leading perceived barriers to adherence included: "family friends don't help me remember/tell me I shouldn't take it" and "forgot". Participants reported that the exercise was useful as it allowed them to better address the challenges faced by paediatric patients and caregivers. Conclusions Promoting good adherence practices among caregivers of children on antiretrovirals is challenging but essential in the treatment of paediatric HIV. Participants in this exercise achieved poor adherence rates, but identified with many of the barriers commonly reported by caregivers. Simulations such as this have the potential to promote awareness of paediatric ARV adherence issues among healthcare staff and ultimately improve adherence support and patient outcomes.

  19. Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review

    Directory of Open Access Journals (Sweden)

    Maia Hightower

    2003-02-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 and type 2 (HIV-2 are the causative agents of AIDS. HIV-2 is prevalent at moderate to high rates in West African countries, such as Senegal, Guinea, Gambia, and Cape Verde. Diagnosis of HIV-2 is made with a positive HIV-1/HIV-2 ELISA or simple/rapid assay, followed by one or two confirmatory tests specific for HIV-2. Following CD4+ T cell counts, HIV-2 viral burden and clinical signs and symptoms of immunodeficiency are beneficial in monitoring HIV-2 disease progression. Although non-nucleoside reverse transcriptase inhibitors are ineffective in treating HIV-2, nucleoside reverse transcriptase inhibitors and protease inhibitors can be effective in dual and triple antiretroviral regimens. Their use can decrease HIV-2 viral load, increase CD4+ T cell counts and improve AIDS-related symptoms. HIV-2 resistance to various nucleoside reverse transcriptase inhibitors and protease inhibitors, including zidovudine, lamivudine, ritonavir and indinavir, has been identified in some HIV-2 infected patients on antiretroviral therapy. The knowledge of HIV-2 peculiarities, when compared to HIV-1, is crucial to helping diagnose and guide the clinician in the choice of the initial antiretroviral regimen and for monitoring therapy success.

  20. Southern African HIV Clinicians Society adult antiretroviral therapy guidelines: Update on when to initiate antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Graeme Meintjes

    2015-04-01

    Full Text Available The most recent version of the Southern African HIV Clinicians Society’s adult antiretroviral therapy (ART guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomised controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults. The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/μL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.

  1. Naive Probability: Model-based Estimates of Unique Events

    Science.gov (United States)

    2014-05-04

    will end the shortage of replacement organs in the next 15 years? 3 the Supreme Court rules on the constitutionality of gay marriage in the next 5...La Mont, K., Lipton, J., Dehaene, S., Kanwisher, N., & Spelke, E.S. (2006). Nonsymbolic arithmetic in adults and young children . Cognition, 98, 199...years? that a gay person will be elected as president in the next 50 years? 4 Greece will make a full economic recovery in the next 10 years

  2. Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Clotet, Bonaventura;

    2008-01-01

    OBJECTIVE(S): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death. DESIGN: Virological failure was defined as experiencing two consecutive viral loads of more than 400......-up. We observed 829 AIDS events and 571 deaths during 38,814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis...

  3. Naive T lymphocytes traffic to inflamed central nervous system, but require antigen recognition for activation

    DEFF Research Database (Denmark)

    Krakowski, M L; Owens, T

    2000-01-01

    Organ-specific autoimmune diseases may be induced by infiltration of the target tissue by CD4(+) T cells with specificity for self antigen(s). As disease progresses, T cells of other specificities appear in the tissue. Traffic of naive, antigen-inexperienced T cells to target tissues has not been...... shown, although many studies have shown extravasation of activated or memory T cells. We have used a novel experimental system to track naive T cells to the central nervous system (CNS) in TCR transgenic mice with adoptively transferred experimental autoimmune encephalomyelitis. Ovalbumin (OVA)-specific...... CD4(+) T cells were equivalent in number to disease-inducing myelin basic protein (MBP)-specific T cells at disease onset. Furthermore, OVA-specific T cells retained a naive phenotype and did not transcribe Th1 cytokines, in contrast to MBP-specific T cells. These findings demonstrate that the T cell...

  4. Expansion of China's free antiretroviral treatment program

    Institute of Scientific and Technical Information of China (English)

    ZHAO De-cai; ZHANG Fu-jie; WEN Yi; MA Ye; ZHAO Yan; ZHANG Yao; WU Ya-song; LIU Xia; Elizabeth Au; LIU Zhong-fu

    2012-01-01

    Background In 2003,China's National Free Antiretroviral Treatment Program (NFATP) was initiated as a pilot,which covered only 100 HIV/AIDS patients.By 2011,the pilot had evolved into a nationwide program and had provided free treatment for over 150 000 patients.The objective of this study was to report and evaluate the progress of China's free antiretroviral treatment program.Methods The NFATP Database was systematically reviewed and a total of 150 692 HIV/AIDS patients were included in this study.Program progress indicators including the number of treated HIV/AIDS patients,follow-up visit rate,CD4 test rate,and viral load test rate were summarized and examined over a calendar year to evaluate the progress of NFATP quantitatively and qualitatively.Results By the end of 2011,a total of 150 692 HIV/AIDS patients had been treated through the NFATP and 122 613 of them were still on treatment.Of all patients,about 72% were enrolled during the past four years.The dominant transmission route was blood related in the early phase of the NFATP,but gradually changed to sexual contact.Besides quantitative improvements,progress indicators also demonstrated significant qualitative improvements that the program had made during the past 9 years.Conclusions Great achievement has been made by China's NFATP.China's experience indicates the importance of a comprehensive response to the success of its treatment program.However,to ensure the quality and sustainability of treatment in the long term,more attention and resources should be paid towards program management.Chin Med J 2012; 125(19):3514-3521

  5. The cost of antiretroviral therapy in Haiti

    Directory of Open Access Journals (Sweden)

    Fitzgerald Daniel W

    2008-02-01

    Full Text Available Abstract Background We determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART to patients with AIDS in Haiti. Methods We examined data from 218 treatment-naïve adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART. Results The mean total cost of treatment per patient was $US 982 including $US 846 in direct costs, $US 114 for overhead, and $US 22 for societal costs. The direct cost per patient included generic ART medications $US 355, lab tests $US 130, nutrition $US 117, hospitalizations $US 62, pre-ART evaluation $US 58, labor $US 51, non-ART medications $US 39, outside referrals $US 31, and telephone cards for patient retention $US 3. Higher treatment costs were associated with hospitalization, change in ART regimen, TB treatment, and survival for one year. We estimate that 1.5 doctors and 2.5 nurses are required to treat 1000 patients in the first year after initiating ART. Conclusion Initial ART treatment in Haiti costs approximately $US 1,000 per patient per year. With generic first-line antiretroviral drugs, only 36% of the cost is for medications. Patients who change regimens are significantly more expensive to treat, highlighting the need for less-expensive second-line drugs. There may be sufficient health care personnel to treat all HIV-infected patients in urban areas of Haiti, but not in rural areas. New models of HIV care are needed for rural areas using assistant medical officers and community health workers.

  6. Global Pharmacovigilance for Antiretroviral Drugs: Overcoming Contrasting Priorities

    OpenAIRE

    Nyasha Bakare; Ivor Ralph Edwards; Andy Stergachis; Shanthi Pal; Holmes, Charles B; Marie Lindquist; Chris Duncombe; Alex Dodoo; Joel Novendstern; Jude Nwokike; Ricardo Kuchenbecker; Aberg, Judith A.; Veronica Miller; Jur Strobos

    2011-01-01

    Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings.

  7. Epidemiology, clinical and laboratory characteristics of currently alive HIV-1 infected former blood donors naive to antiretroviral therapy in Anhui Province, China

    Institute of Scientific and Technical Information of China (English)

    XU Jian-qing; SU Bing; DING Xin-ping; GAO Bing; GU Yong-bin; CAO Xiao-yun; XING Hui; HONG Kun-xue; PENG Hong; ZHAO Quan-bi; YUAN Lin; WANG Jian-jun; FENG Yi; ZHANG Gui-yun; MA Li-ying; WU Lan; SHAO Yi-ming; HAN Li-feng; XU Chen; RUAN Yu-hua; XU Zhen-hou; CHEN Xi; LIU Zhen-dong; WANG Jun

    2006-01-01

    Background Unregulated commercial blood/plasma collection among farmers occurred between 1992 and 1995 in central China and caused the second major epidemic of human immunodeficiency virus type 1 (HIV-1)infection in China. It is important to characterize HIV-1-infected former blood donors and to study characteristics associated with disease progression for future clinical intervention and vaccine development.Methods A cross-sectional study was performed on HIV-1-infected former blood donors (FBDs) and age-matched HIV-seronegative local residents. Demographic, epidemiologic, clinical and key laboratory data were collected from all study participants. Both unadjusted and adjusted multivariate linear regressions were employed to analyze the association of the decrease of CD4+ T-cell counts with other characteristics.Results Two hundred and ninety-four HIV-1-infected FBDs and 59 age-matched HIV-seronegative local residents were enrolled in this study. The unregulated blood/plasma collection occurred more than a decade (10.8- 12.8 years) ago, which caused the rapid spread of HIV-1 infection and the high prevalence of co-infection with hepatitis C virus (HCV, 89.5%); hepatitis B virus (HBV) co-infection was observed in only 11 HIV+participants (3.7%). Deterioration in both clinical manifestation and laboratory parameters and increase of viral loads were observed in parallel with the decrease of CD4+ T-cell counts. The decrease of total lymphocyte counts (P<0.001)and hemoglobin levels (P<0.001) and the appearance of dermatosis (P=0.03) were observed in parallel with the decrease of CD4+ T-cell counts whereas viral loads (P<0.001) and CD8+ T-cell counts (P=0.01) were inversely associated with CD4+ T-cell counts.Conclusions Co-infection with HCV but not HBV is highly prevalent among HIV-1-infected FBDs. CD4+ T-cell counts is a reliable indicator for disease progression among FBDs. Total lymphocyte counts, hemoglobin level and appearance of dermatosis were positively, whereas CD8+ T-cell counts and viral loads were inversely associated with the decreased CD4+ T-cell counts.

  8. Is it time to revise antiretrovirals dosing? a pharmacokinetic viewpoint.

    Science.gov (United States)

    Cattaneo, Dario; Baldelli, Sara; Castoldi, Simone; Charbe, Nitin; Cozzi, Valeria; Fucile, Serena; Clementi, Emilio

    2014-10-23

    We document our experience with therapeutic drug monitoring (TDM) of antiretroviral agents (1807 determinations) carried out as day-by-day clinical practice for the optimization of drug dosing in HIV-infected patients. A significant proportion of patients had lopinavir, atazanavir and nevirapine trough concentrations exceeding the upper therapeutic threshold. Further studies are needed to identify good candidates/drugs for TDM, eventually allowing the selection of patients who may benefit from TDM-driven adjustments in antiretrovirals dosage.

  9. Adherence to antiretroviral therapy among people living with HIV

    Directory of Open Access Journals (Sweden)

    Basavaprabhu Achappa

    2013-01-01

    Full Text Available Background: Acquired immune deficiency syndrome (AIDS is now considered as a manageable chronic illness. There has been a dramatic reduction in human immunodeficiency virus (HIV related morbidity and mortality due to antiretroviral therapy. A high level of adherence (>95% is required for antiretroviral therapy to be effective. There are many barriers to adherence in both developed and developing countries. Aim: The aim of our study was to determine adherence levels and factors influencing adherence to antiretroviral therapy among people living with HIV. Materials and Methods: Using a cross-sectional study design, 116 HIV positive patients receiving antiretroviral therapy for at least 1 year were interviewed using a semi structured questionnaire. The collected data was analyzed using Statistical Product and Service Solutions (SPSS version 11.5. Chi-square test was done. A P value of < 0.05 was considered statistically significant. Results: Of 116 participants, 63.7% reported adherence ≥ 95%. Mean adherence index was 91.25%. Financial constraints, forgetting to take medication, lack of family care, depression, alcohol use, social stigma and side effects to antiretroviral therapy were barriers for adherence in our study. Conclusion: Adherence to antiretroviral therapy in south India is suboptimal. Intensive adherence counseling should be provided to all patients before initiation ofantiretroviral therapy. Health care providers must identify possible barriers to adherence at the earliest and provide appropriate solutions.

  10. Clinical outcomes and immune reconstitution in 103 advanced AIDS patients undergoing 12-month highly active antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    DAI Yi; QIU Zhi-feng; LI Tai-sheng; HAN Yang; ZUO Ling-yan; XIE Jing; MA Xiao-jun; LIU Zheng-yin; WANG Ai-xia

    2006-01-01

    Background Highly active antiretroviral therapy (HAART) roduces profound suppression of HIV replication, substantial increase in CD4+ T cells, and partial reconstitution of the immune system. However, the numbers of subjects were small in previous Chinese studies. This study evaluated the efficacy and side effects of HAART in Chinese advanced AIDS patients.Methods One hundred and three antiretroviral drug naive AIDS patients were enrolled in this study and were divided into two groups by their baseline CD4+ count: <100 cells/ μl or ≥ 100 cells/μl. Clinical, virological and immunological outcomes were monitored at baseline and at 1, 3, 6, 9 and 12 months during the course of treatment with HAART.Results One patient died and another was lost from the follow-up. For the remaining 101 HIV/AIDS patients at the 12th month during the HAART, the plasma viral load (VL) was reduced to (3.2±0.7) lg copies/ml, the CD4+ count increased to (168±51) cells/μl [among which the naive phenotype (CD45RA+CD62L+) increased to (49±27) cells/μl and the memory phenotype (CD45RA ̄) increased to (119±55) cells/μl], and the percentage of CD4+CD28+ cells increased. At the same time, there was a significant reduction of CD8+ T cell activation. In the 69 patients with the baseline CD4+ count <100 cells/μl, 37 had a VL <50 copies/ml; while in the 34 patients with the baseline CD4+ count ≥ 100 cells/μl, 25 had a VL <50 copies/ml, the difference between the two groups was statistically significant. The CD4+ T cell count showed a two-phase increase during HAART and a significant positive correlation was shown between the change of CD4+ count and plasma VL. Over 12 months of HAART,10 patients had gastrointestinal side effects, 13 peripheral neuritis, 7 hepatic lesions, 8 hematological side effects,8 skin rashes, 10 lipodystrophy and 1 renal calculus.Conclusions Immune reconstitution as well as the significantly improved clinical outcomes is observed in Chinese advanced AIDS

  11. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations of the Panel on Clinical Practices for Treatment of HIV.

    Science.gov (United States)

    Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

    2002-05-17

    The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. Treatment should

  12. Children's Naive Theories of Intelligence Influence Their Metacognitive Judgments

    Science.gov (United States)

    Miele, David B.; Son, Lisa K.; Metcalfe, Janet

    2013-01-01

    Recent studies have shown that the metacognitive judgments adults infer from their experiences of encoding effort vary in accordance with their naive theories of intelligence. To determine whether this finding extends to elementary schoolchildren, a study was conducted in which 27 third graders (M[subscript age] = 8.27) and 24 fifth graders…

  13. Test of the Universality of Naive-Time-Reversal-Odd Fragmentation Functions

    NARCIS (Netherlands)

    Boer, Daniel; Kang, Zhong-Bo; Vogelsang, Werner; Yuan, Feng

    2010-01-01

    We investigate the "spontaneous'' hyperon transverse polarization in e(+)e(-) annihilation and semi-inclusive deep inelastic scattering processes as a test of the universality of the naive-time-reversal-odd transverse momentum dependent fragmentation functions. We find that universality implies defi

  14. PERBANDINGAN K-NEAREST NEIGHBOR DAN NAIVE BAYES UNTUK KLASIFIKASI TANAH LAYAK TANAM POHON JATI

    Directory of Open Access Journals (Sweden)

    Didik Srianto

    2016-10-01

    Full Text Available Data mining adalah proses menganalisa data dari perspektif yang berbeda dan menyimpulkannya menjadi informasi-informasi penting yang dapat dipakai untuk meningkatkan keuntungan, memperkecil biaya pengeluaran, atau bahkan keduanya. Secara teknis, data mining dapat disebut sebagai proses untuk menemukan korelasi atau pola dari ratusan atau ribuan field dari sebuah relasional database yang besar. Pada perum perhutani KPH SEMARANG saat ini masih menggunakan cara manual untuk menentukan jenis tanaman (jati / non jati. K-Nearest Neighbour atau k-NN merupakan algoritma data mining yang dapat digunakan untuk proses klasifikasi dan regresi. Naive bayes Classifier merupakan suatu teknik yang dapat digunakan untuk teknik klasifikasi. Pada penelitian ini k-NN dan Naive Bayes akan digunakan untuk mengklasifikasi data pohon jati dari perum perhutani KPH SEMARANG. Yang mana hasil klasifikasi dari k-NN dan Naive Bayes akan dibandingkan hasilnya. Pengujian dilakukan menggunakan software RapidMiner. Setelah dilakukan pengujian k-NN dianggap lebih baik dari Naife Bayes dengan akurasi 96.66% dan 82.63. Kata kunci -k-NN,Klasifikasi,Naive Bayes,Penanaman Pohon Jati

  15. Effects of Noise Suppression on Intelligibility: Experts' Opinions and Naive Normal-Hearing Listeners' Performance

    Science.gov (United States)

    Hilkhuysen, Gaston L. M.; Gaubitch, Nikolay; Huckvale, Mark

    2013-01-01

    Purpose: In this study, the authors investigated how well experts can adjust the settings of a commercial noise-reduction system to optimize the intelligibility for naive normal-hearing listeners. Method: In Experiment 1, 5 experts adjusted parameters for a noise-reduction system while aiming to optimize intelligibility. The stimuli consisted of…

  16. The Effect of Naive Ideas on Students' Reasoning about Electricity and Magnetism

    Science.gov (United States)

    Leppavirta, Johanna

    2012-01-01

    Traditional multiple-choice concept inventories measure students' critical conceptual understanding and are designed to reveal students' naive or alternate ideas. The overall scores, however, give little information about the state of students' knowledge and the consistency of reasoning. This study investigates whether students have consistent…

  17. Providing probability distributions for the causal pathogen of clinical mastitis using naive Bayesian networks

    NARCIS (Netherlands)

    Steeneveld, W.; Gaag, van der L.C.; Barkema, H.W.; Hogeveen, H.

    2009-01-01

    Clinical mastitis (CM) can be caused by a wide variety of pathogens and farmers must start treatment before the actual causal pathogen is known. By providing a probability distribution for the causal pathogen, naive Bayesian networks (NBN) can serve as a management tool for farmers to decide which t

  18. Erk5 Is a Key Regulator of Naive-Primed Transition and Embryonic Stem Cell Identity

    Directory of Open Access Journals (Sweden)

    Charles A.C. Williams

    2016-08-01

    Full Text Available Embryonic stem cells (ESCs can self-renew or differentiate into any cell type, a phenomenon known as pluripotency. Distinct pluripotent states, termed naive and primed pluripotency, have been described. However, the mechanisms that control naive-primed pluripotent transition are poorly understood. Here, we perform a targeted screen for kinase inhibitors, which modulate the naive-primed pluripotent transition. We find that XMD compounds, which selectively inhibit Erk5 kinase and BET bromodomain family proteins, drive ESCs toward primed pluripotency. Using compound selectivity engineering and CRISPR/Cas9 genome editing, we reveal distinct functions for Erk5 and Brd4 in pluripotency regulation. We show that Erk5 signaling maintains ESCs in the naive state and suppresses progression toward primed pluripotency and neuroectoderm differentiation. Additionally, we identify a specialized role for Erk5 in defining ESC lineage selection, whereby Erk5 inhibits a cardiomyocyte-specific differentiation program. Our data therefore reveal multiple critical functions for Erk5 in controlling ESC identity.

  19. Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates.

    Science.gov (United States)

    Cicin-Sain, Luka; Smyk-Pearson, Susan; Smyk-Paerson, Sue; Currier, Noreen; Byrd, Laura; Koudelka, Caroline; Robinson, Tammie; Swarbrick, Gwendolyn; Tackitt, Shane; Legasse, Alfred; Fischer, Miranda; Nikolich-Zugich, Dragana; Park, Byung; Hobbs, Theodore; Doane, Cynthia J; Mori, Motomi; Axthelm, Michael K; Axthelm, Michael T; Lewinsohn, Deborah A; Nikolich-Zugich, Janko

    2010-06-15

    Aging is usually accompanied by diminished immune protection upon infection or vaccination. Although aging results in well-characterized changes in the T cell compartment of long-lived, outbred, and pathogen-exposed organisms, their relevance for primary Ag responses remain unclear. Therefore, it remains unclear whether and to what extent the loss of naive T cells, their partial replacement by oligoclonal memory populations, and the consequent constriction of TCR repertoire limit the Ag responses in aging primates. We show in this study that aging rhesus monkeys (Macaca mulatta) exhibit poor CD8 T cell and B cell responses in the blood and poor CD8 responses in the lungs upon vaccination with the modified vaccinia strain Ankara. The function of APCs appeared to be maintained in aging monkeys, suggesting that the poor response was likely intrinsic to lymphocytes. We found that the loss of naive CD4 and CD8 T cells, and the appearance of persisting T cell clonal expansions predicted poor CD8 responses in individual monkeys. There was strong correlation between early CD8 responses in the transitory CD28+ CD62L- CD8+ T cell compartment and the peak Ab titers upon boost in individual animals, as well as a correlation of both parameters of immune response to the frequency of naive CD8+ T cells in old but not in adult monkeys. Therefore, our results argue that T cell repertoire constriction and naive cell loss have prognostic value for global immune function in aging primates.

  20. Anterior Cingulate Volumetric Alterations in Treatment-Naive Adults with ADHD: A Pilot Study

    Science.gov (United States)

    Makris, Nikos; Seidman, Larry J.; Valera, Eve M.; Biederman, Joseph; Monuteaux, Michael C.; Kennedy, David N.; Caviness, Verne S., Jr.; Bush, George; Crum, Katherine; Brown, Ariel B.; Faraone, Stephen V.

    2010-01-01

    Objective: We sought to examine preliminary results of brain alterations in anterior cingulate cortex (ACC) in treatment-naive adults with ADHD. The ACC is a central brain node for the integration of cognitive control and allocation of attention, affect and drive. Thus its anatomical alteration may give rise to impulsivity, hyperactivity and…

  1. Observation of the naive-T-odd Sivers effect in deep-inelastic scattering.

    Science.gov (United States)

    Airapetian, A; Akopov, N; Akopov, Z; Aschenauer, E C; Augustyniak, W; Avetissian, A; Avetisyan, E; Bacchetta, A; Ball, B; Bianchi, N; Blok, H P; Böttcher, H; Bonomo, C; Borissov, A; Bryzgalov, V; Burns, J; Capiluppi, M; Capitani, G P; Cisbani, E; Ciullo, G; Contalbrigo, M; Dalpiaz, P F; Deconinck, W; De Leo, R; De Nardo, L; De Sanctis, E; Diefenthaler, M; Di Nezza, P; Dreschler, J; Düren, M; Ehrenfried, M; Elbakian, G; Ellinghaus, F; Elschenbroich, U; Fabbri, R; Fantoni, A; Felawka, L; Frullani, S; Gabbert, D; Gapienko, G; Gapienko, V; Garibaldi, F; Gharibyan, V; Giordano, F; Gliske, S; Hadjidakis, C; Hartig, M; Hasch, D; Hill, G; Hillenbrand, A; Hoek, M; Holler, Y; Hristova, I; Imazu, Y; Ivanilov, A; Jackson, H E; Jo, H S; Joosten, S; Kaiser, R; Keri, T; Kinney, E; Kisselev, A; Korotkov, V; Kozlov, V; Kravchenko, P; Lagamba, L; Lamb, R; Lapikás, L; Lehmann, I; Lenisa, P; Linden-Levy, L A; López Ruiz, A; Lorenzon, W; Lu, X-G; Lu, X-R; Ma, B-Q; Mahon, D; Makins, N C R; Manaenkov, S I; Manfré, L; Mao, Y; Marianski, B; Martinez de la Ossa, A; Marukyan, H; Miller, C A; Miyachi, Y; Movsisyan, A; Murray, M; Mussgiller, A; Nappi, E; Naryshkin, Y; Nass, A; Negodaev, M; Nowak, W-D; Pappalardo, L L; Perez-Benito, R; Reimer, P E; Reolon, A R; Riedl, C; Rith, K; Rosner, G; Rostomyan, A; Rubin, J; Ryckbosch, D; Salomatin, Y; Sanftl, F; Schäfer, A; Schnell, G; Schüler, K P; Seitz, B; Shibata, T-A; Shutov, V; Stancari, M; Statera, M; Steijger, J J M; Stenzel, H; Stewart, J; Stinzing, F; Taroian, S; Terkulov, A; Trzcinski, A; Tytgat, M; Vandenbroucke, A; van der Nat, P B; Van Haarlem, Y; Van Hulse, C; Varanda, M; Veretennikov, D; Vikhrov, V; Vilardi, I; Vogel, C; Wang, S; Yaschenko, S; Ye, H; Ye, Z; Yen, S; Yu, W; Zeiler, D; Zihlmann, B; Zupranski, P

    2009-10-09

    Azimuthal single-spin asymmetries of leptoproduced pions and charged kaons were measured on a transversely polarized hydrogen target. Evidence for a naive-T-odd, transverse-momentum-dependent parton distribution function is deduced from nonvanishing Sivers effects for pi(+), pi(0), and K(+/-), as well as in the difference of the pi(+) and pi(-) cross sections.

  2. Using Unsupervised Learning to Improve the Naive Bayes Classifier for Wireless Sensor Networks

    NARCIS (Netherlands)

    Zwartjes, G.J.; Havinga, P.J.M.; Smit, G.J.M.; Hurink, J.L.

    2012-01-01

    Online processing is essential for many sensor network applications. Sensor nodes can sample far more data than what can practically be transmitted using state of the art sensor network radios. Online processing, however, is complicated due to limited resources of individual nodes. The naive Bayes c

  3. Favorable therapeutic response with an antiretroviral salvage regimen in an HIV-1-positive subject infected with a CRF11-cpx virus.

    Science.gov (United States)

    Tau, Pamela; Mancon, Alessandro; Mileto, Davide; Di Nardo Stuppino, Silvia; Bottani, Giulia; Gismondo, Maria Rita; Galli, Massimo; Micheli, Valeria; Rusconi, Stefano

    2014-05-01

    HIV drug resistance still represents a crucial problem in antiretroviral therapy. We report a case of a naive patient, harboring a CRF11-cpx virus, which showed drug resistance mutations in the reverse transcriptase. A drug resistance genotyping test was performed for the pol (protease, reverse transcriptase, and integrase) and V3 regions. The initial clinical parameter results showed a 4 log level of HIV-RNA (12,090 cp/ml) and a very low CD4(+) cell count (35 cells/μl). We designed an initial highly active antiretroviral therapy (HAART) regimen including lamivudine (3TC)+abacavir (ABC)+booster ritonavir (DRV/r). The virus was highly resistant to all nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) except for ABC, tenofovir (TDF), and efavirenz (EFV) and was susceptible to all protease inhibitors (PIs) and integrase inhibitors (INIs). A salvage regimen including raltegravir (RAL)+DRV/r was started. Ten months later, the immunovirological status shows CD4(+) 142/μl and HIV-RNA <37 cp/ml. Our results demonstrate the effectiveness of a treatment combination that includes RAL+DRV/r in a patient infected with a complex X4-tropic CRF11-cpx virus.

  4. Herpes simplex virus type 2 (HSV-2) genital shedding in HSV-2-/HIV-1-co-infected women receiving effective combination antiretroviral therapy.

    Science.gov (United States)

    Péré, Héléne; Rascanu, Aida; LeGoff, Jérome; Matta, Mathieu; Bois, Frédéric; Lortholary, Olivier; Leroy, Valériane; Launay, Odile; Bélec, Laurent

    2016-03-01

    The dynamics of genital shedding of HSV-2 DNA was assessed in HIV-1-infected women taking combination antiretroviral therapy (cART). HIV-1 RNA, HIV-1 DNA and HSV DNA loads were measured during 12-18 months using frozen plasma, PBMC and cervicovaginal lavage samples from 22 HIV-1-infected women, including 17 women naive for antiretroviral therapy initiating cART and 5 women with virological failure switching to a new regimen. Nineteen (86%) women were HSV-2-seropositive. Among HSV-2-/HIV-1-co-infected women, HIV-1 RNA loads showed a rapid fall from baseline after one month of cART, in parallel in paired plasma and cervicovaginal secretions. In contrast, HIV-1 DNA loads did not show significant variations from baseline up to 18 months of treatment in both systemic and genital compartments. HSV DNA was detected at least once in 12 (63%) of 19 women during follow up: HSV-2 shedding in the genital compartment was observed in 11% of cervicovaginal samples at baseline and in 16% after initiating or switching cART. Cervicovaginal HIV-1 RNA loads were strongly associated with plasma HIV-1 RNA loads over time, but not with cervicovaginal HSV DNA loads. Reactivation of genital HSV-2 replication frequently occurred despite effective cART in HSV-2-/HIV-1-co-infected women. Genital HSV-2 replication under cART does not influence cervicovaginal HIV-1 RNA or DNA shedding.

  5. The incidence rate of HIV type-1 drug resistance in patients on antiretroviral therapy: a nationwide population-based Danish cohort study 1999-2005

    DEFF Research Database (Denmark)

    Audelin, A.M.; Lohse, N.; Obel, N.;

    2009-01-01

    BACKGROUND: Newer antiretroviral treatment regimens for HIV carry a lower risk of inducing drug resistance mutations. We estimated changes in incidence rates (IRs) of new mutations in HIV-infected individuals receiving highly active antiretroviral therapy (HAART). METHODS: Population-based data...... were obtained from the Danish HIV Cohort Study and the Danish HIV Sequence Database. We included treatment-naive patients initiating HAART after December 1997 and computed time to first drug resistance mutation, identified as new mutations detected within 1 year after a 60-day period of treatment.......077). The IR of PI resistance decreased from 7.5 (1.4-21.8) in 1999 to 2.9 (0.7-11.4) in 2002-2003 (P=0.148). The IRs were low for specific resistance mutations, except for M184V (IR 5.6 [4.0-7.9]) and K103N (IR 8.2 [5.6-12.0]). CONCLUSIONS: The incidence of acquired drug resistance has decreased among HIV...

  6. HIV-infected individuals with co-occurring bipolar disorder evidence poor antiretroviral and psychiatric medication adherence.

    Science.gov (United States)

    Moore, David J; Posada, Carolina; Parikh, Mili; Arce, Miguel; Vaida, Florin; Riggs, Patricia K; Gouaux, Ben; Ellis, Ronald J; Letendre, Scott L; Grant, Igor; Atkinson, J Hampton

    2012-11-01

    The contribution of bipolar disorder (BD), a prevalent serious mental illness characterized by impulsivity and mood instability, to antiretroviral (ART) and psychiatric medication adherence among HIV-infected (HIV+) individuals is unknown. We examined medication adherence among 44 HIV+/BD+ persons as compared to 33 demographically- and medically-comparable HIV+/BD- persons. Classification of adherent (≥ 90%) or non-adherent (ART adherent (47.7%) as compared to HIV+/BD- (90.9%) persons. Within the HIV+/BD+ group, mean psychiatric medication adherence was significantly worse than ART medication adherence, although there was a significant correlation between ART and psychiatric adherence levels. Importantly, 30-day ART adherence was associated with plasma virologic response among HIV+/BD+ individuals. Given the high overlap of HIV and BD, and the observed medication adherence difficulties for these persons, specialized adherence improvement interventions are needed.

  7. Plasma and Intracellular Antiretroviral Concentrations in HIV-Infected Patients under Short Cycles of Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Laura Zehnacker

    2014-01-01

    Full Text Available Study of plasma and intracellular concentrations of atazanavir, lopinavir, nevirapine, and efavirenz was conducted on 48 patients under short cycles of antiretroviral therapy. Intracellular concentrations (IC were still measurable for all drugs after 85 h or 110 h drug intake despite the absence of drug in plasma for atazanavir and lopinavir. A linear relationship between plasma and intracellular efavirenz was observed. Further studies to fully understand the impact of IC in the intermittent antiviral treatment are required.

  8. Durability of first antiretroviral treatment in HIV chronically infected patients: why change and what are the outcomes?

    Directory of Open Access Journals (Sweden)

    Patricia Moniz

    2014-11-01

    Full Text Available Introduction: First antiretroviral therapy (ART is often switched to simpler, more potent or better tolerated regimens (1, 2. Although discontinuation rates are frequently studied, the durability of regimens is rarely approached. Materials and Methods: Retrospective study with the following objectives: analyze first ART schemes and their durability in naive patients with chronic HIV-1 and 2 infections, evaluate factors influencing ART change, second-line ART and consequent virologic and immunologic responses. Patients had follow-ups in a Central University Hospital, started ART between January 2007 and December 2012 and changed first regimens. Clinical data was obtained from medical records and analyzed using the Statistical Package for the Social Sciences (version 20. Results: Of the 652 naive patients who started ART, 164 changed regimens. The majority had HIV-1 infection (n=158. The mean age was 43.9 years (standard deviation±14.3, with a male predominance of 57.9%. Regimens with efavirenz were the most common amongst HIV-1 patients (50% followed by lopinavir/r (22%. In HIV-2 patients, lopinavir/r (n=3 regimens were most prevalent. First ART regimens had a mean duration of 12.1 months. There was no difference between NNRTI (59.8% and protease inhibitor (40.2% schemes regarding durability. Adverse reactions were the major cause of ART switching (55.5% followed by therapy resistance (12.1%. Age was inversely related to durability (p=0.007 Mann-Whitney, Phi coefficient −0.161 and associated with the appearance of adverse reactions (p=0.04, Chi-square. Younger patients had a reduced risk of adverse reactions by 27%. Adverse reactions increased the risk of inferior durability by 40%. Psychiatric symptoms (28.4% were the most prevalent, all attributed to efavirenz. The year of ART initiation was associated with different durability rates (p=0.005, Mann-Whitney. Patients started on ART before the year 2010 reduced the probability of inferior ART

  9. Opportunistic infections in relation to antiretroviral status among AIDS patients from south India

    Directory of Open Access Journals (Sweden)

    S Srirangaraj

    2011-01-01

    Full Text Available Background: There is a need to generate data from India on relative frequencies of specific opportunistic infections (OIs in different regions and their relation to the choice of commonly used generic highly active anti-retroviral therapy (HAART regimens. Objectives: To document the prevailing prevalence pattern of OIs both before and after HAART, to look for reduction in OIs following HAART, to assess the risk of developing new OIs within 6 months of HAART initiation and to see if there is any difference in the risk of developing a new OI within 6 months of HAART initiation, for those on Efavirenz (EFV-based regimens and Nevirapine (NVP-based regimens. Materials and Methods: In a prospective observational cohort study conducted in South India involving 108 ART-naive AIDS patients, different pathogens were isolated and identified using standard laboratory techniques. Data analysis was done using SPSS software (version 16.0. Risk of developing an OI after HAART initiation was assessed using the likelihood ratio test from Cox regression models. Results: Tuberculosis (53.4%, oral Candidiasis (27.2% and Herpes Zoster (14.7% were the common infections seen. There was a drastic reduction of 96.59% in OI events after 6 months of HAART. The risk of developing an OI within 6 months of HAART initiation was 5.56%. Time to development of an OI in the first 6 months of HAART was shorter for the NVP-based regimens than with EFV-based regimens, but this difference was not statistically significant (HR=0.891, 95% CI: 0.179-4.429; P=0.888. Conclusion: Tuberculosis is the most important OI before initiation of HAART. Both EFV and NVP-based regimens are equally efficacious in controlling OIs.

  10. Unanticipated Effects of New Drug Availability on Antiretroviral Durability: Implications for Comparative Effectiveness Research.

    Science.gov (United States)

    Eaton, Ellen F; Tamhane, Ashutosh R; Burkholder, Greer A; Willig, James H; Saag, Michael S; Mugavero, Michael J

    2016-04-01

    Background.  Durability of antiretroviral (ARV) therapy is associated with improved human immunodeficiency virus (HIV) outcomes. Data on ARV regimen durability in recent years and clinical settings are lacking. Methods.  This retrospective follow-up study included treatment-naive HIV-infected patients initiating ARV therapy between January 2007 and December 2012 in a university-affiliated HIV clinic in the Southeastern United States. Outcome of interest was durability (time to discontinuation) of the initial regimen. Durability was evaluated using Kaplan-Meier survival analyses. Cox proportional hazard analyses was used to evaluate the association among durability and sociodemographic, clinical, and regimen-level factors. Results.  Overall, 546 patients were analyzed. Median durability of all regimens was 39.5 months (95% confidence interval, 34.1-44.4). Commonly prescribed regimens were emtricitabine and tenofovir with efavirenz (51%; median duration = 40.1 months) and with raltegravir (14%; 47.8 months). Overall, 67% of patients had an undetectable viral load at the time of regimen cessation. Discontinuation was less likely with an integrase strand transfer inhibitor (adjusted hazards ratio [aHR] = 0.35, P = .001) or protease inhibitor-based regimen (aHR = 0.45, P = .006) and more likely with a higher pill burden (aHR = 2.25, P = .003) and a later treatment era (aHR = 1.64, P new drug availability and provider preference. Medication durability must be interpreted carefully in the context of a dynamic treatment landscape.

  11. Patient-reported barriers and facilitators to antiretroviral adherence in sub-Saharan Africa

    Science.gov (United States)

    Croome, Natasha; Ahluwalia, Monisha; Hughes, Lyndsay D.; Abas, Melanie

    2017-01-01

    Objective: The aim of this study was to identify the range and frequency of patient-reported barriers and facilitators to antiretroviral treatment (ART) adherence in sub-Saharan Africa (SSA). Design: Studies from 2005 to 2016 were identified by searching 10 electronic databases and through additional hand and web-searching. Methods: Inclusion criteria were HIV-positive adults taking ART based in any SSA country, qualitative study or quantitative survey and included at least one patient-reported barrier or facilitator to ART adherence. Exclusion criteria were only including data from treatment-naive patients initiating ART, only single-dose treatment, participants residing outside of SSA and reviews. Results: After screening 11 283 records, 154 studies (161 papers) were included in this review. Forty-three barriers and 30 facilitators were reported across 24 SSA countries. The most frequently identified barriers across studies were forgetting (n = 76), lack of access to adequate food (n = 72), stigma and discrimination (n = 68), side effects (n = 67) and being outside the house or travelling (n = 60). The most frequently identified facilitators across studies were social support (n = 60), reminders (n = 55), feeling better or healthier after taking ART (n = 35), disclosing their HIV status (n = 26) and having a good relationship with a health provider (n = 22). Conclusion: This review addresses the gap in knowledge by collating all the patient-reported barriers and facilitators to ART adherence in SSA. Current barriers measures need to be adapted or new tools developed to include the wide variety of factors identified. The factors that have the greatest impact need to be isolated so interventions are developed that reduce the barriers and enhance the facilitators. PMID:28121707

  12. Clinically relevant transmitted drug resistance to first line antiretroviral drugs and implications for recommendations.

    Directory of Open Access Journals (Sweden)

    Susana Monge

    Full Text Available BACKGROUND: The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR defined by the 2009 update of the WHO SDRM list. METHODS: We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain between 2007-2011. Using the Stanford algorithm "Low-level resistance", "Intermediate resistance" and "High-level resistance" categories were considered as "Resistant". RESULTS: 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8-7.7], and 221 harbored TDR using the WHO list [7.9% (6.9-9.0]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8-2.9 vs. 3.6% (2.9-4.3 by the WHO list] and PIs [0.8% (0.4-1.1 vs. 1.7% (1.2-2.2], while it was higher for NNRTIs [4.6% (3.8-5.3 vs. 3.7% (3.0-4.7]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02. CONCLUSIONS: Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.

  13. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Kirk, Ole; Reiss, Peter

    2010-01-01

    OBJECTIVES:: Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD. DESIGN:: A cohort study including 6843 HIV-positive persons...... with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards. METHODS:: CKD was defined as either confirmed (two measurements >/=3 months apart) estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m or below for persons with baseline eGFR of above...... 60 ml/min per 1.73 m or confirmed 25% decline in eGFR for persons with baseline eGFR of 60 ml/min per 1.73 m or less, using the Cockcroft-Gault formula. Poisson regression was used to determine factors associated with CKD. RESULTS:: Two hundred and twenty-five (3.3%) persons progressed to CKD during...

  14. Approaches to antiretroviral therapy in China

    Institute of Scientific and Technical Information of China (English)

    Bruce L GILLIAM; Robert R REDFIELD

    2005-01-01

    China has recognized the threat of HIV to its population and responded with a national antiretroviral treatment (ART)program. However, high ART failure rates and the spread of resistance within populations are important realities to consider when developing and managing ART programs in China and worldwide. Concepts which will define treatment success and local and national programmatic goals are 1) access to ART, 2) durability of ART at the patient level, 3)scalability of treatment modalities, and the 4) sustainability of the program at the community or national level. In the face of limited resources, China must also consider when to start ARV therapy, which agents to use, when to switch them, and how to treat highly experienced patients with drug resistance. The optimal ARV regimen to start with is changing frequently with the introduction of new agents and the presentation of new data. Currently, a regimen including tenofovir, emtricitabine or lamivudine and a nonnucleoside reverse transcriptase inhibitor appears to have optimal characteristics to treat HIV/AIDS in China. However, critical to all of these choices is the evaluation of programs implemented to insure wide scale success. China has wisely begun this process of evaluating the performance of local programs through systematic monitoring and evaluation of treatment outcomes. This will allow regimens and programs that work to be expanded, and programs with high failure rates to be eliminated. In the end,evidence based data supporting treatment strategies will allow China to successfully confront its AIDS epidemic early and prevent its tragic consequences

  15. Adesão à terapia antiretroviral para HIV/AIDS Adhesión a la terapia anti-retroviral para el vih/sida Adherence to the antiretroviral therapy for HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Maria Rosa Ceccato Colombrini

    2006-12-01

    que contribuyen a la construcción y ejercicio de la ciudadanía.The non-adherence to the highly active antiretroviral therapy (HAART is considered one of the most threatening risks for the effectiveness of the treatment of the person with HIV/AIDS on the individual plan and for the resistance-virus dissemination on the collective plan. The objective of this study was to analyze, through a literature review, the predicting factors of non-adherence to the HAART, as well as to assemble and relate them to the person in treatment, the disease, the treatment and the health and social support service. The literature points to the need for studies that evaluate social-cultural aspects, beliefs, quality of the service and the relationship of the patient with the multi-professional team, as well as others related to race and to the side effects of the antiretroviral agents. These studies aim at favoring the creation of strategies that im-prove the adherence of patients to the HAART, contributing at the same time for the development and the exercise of citizenship.

  16. Decline in HIV infectivity following the introduction of highly active antiretroviral therapy

    Science.gov (United States)

    Porco, Travis C.; Martin, Jeffrey N.; Page-Shafer, Kimberly A.; Cheng, Amber; Charlebois, Edwin; Grant, Robert M.; Osmond, Dennis H.

    2008-01-01

    Objective Little is known about the degree to which widespread use of antiretroviral therapy in a community reduces uninfected individuals’ risk of acquiring HIV. We estimated the degree to which the probability of HIV infection from an infected partner (the infectivity) declined following the introduction of highly active antiretroviral therapy (HAART) in San Francisco. Design Homosexual men from the San Francisco Young Men’s Health Study, who were initially uninfected with HIV, were asked about sexual practices, and tested for HIV antibodies at each of four follow-up visits during a 6-year period spanning the advent of widespread use of HAART (1994 to 1999). Methods We estimated the infectivity of HIV (per-partnership probability of transmission from an infected partner) using a probabilistic risk model based on observed incident infections and self-reported sexual risk behavior, and tested the hypothesis that infectivity was the same before and after HAART was introduced. Results A total of 534 homosexual men were evaluated. Decreasing trends in HIV seroincidence were observed despite increases in reported number of unprotected receptive anal intercourse partners. Conservatively assuming a constant prevalence of HIV infection between 1994 and 1999, HIV infectivity decreased from 0.120 prior to widespread use of HAART, to 0.048 after the widespread use of HAART – a decline of 60% (P = 0.028). Conclusions Use of HAART by infected persons in a community appears to reduce their infectiousness and therefore may provide an important HIV prevention tool. PMID:15090833

  17. A systematic review of antiretroviral adherence interventions for HIV-infected people who use drugs.

    Science.gov (United States)

    Binford, Meredith Camp; Kahana, Shoshana Y; Altice, Frederick L

    2012-12-01

    HIV-infected persons who use drugs (PWUDs) are particularly vulnerable for suboptimal combination antiretroviral therapy (cART) adherence. A systematic review of interventions to improve cART adherence and virologic outcomes among HIV-infected PWUDs was conducted. Among the 45 eligible studies, randomized controlled trials suggested directly administered antiretroviral therapy, medication-assisted therapy (MAT), contingency management, and multi-component, nurse-delivered interventions provided significant improved short-term adherence and virologic outcomes, but these effects were not sustained after intervention cessation. Cohort and prospective studies suggested short-term increased cART adherence with MAT. More conclusive data regarding the efficacy on cART adherence and HIV treatment outcomes using cognitive behavioral therapy, motivational interviewing, peer-driven interventions and the integration of MAT into HIV clinical care are warranted. Of great concern was the virtual lack of interventions with sustained post-intervention adherence and virologic benefits. Future research directions, including the development of interventions that promote long-term improvements in adherence and virologic outcomes, are discussed.

  18. The Effects Of Antiretroviral Drugs On The Absorbance Characteristics Of Blood Components

    Directory of Open Access Journals (Sweden)

    O. I. Ani

    2015-08-01

    Full Text Available Abstract The effects of antiretroviral drugs on the absorbance characteristics of blood components have been studied. The methodology involved the serial dilution of the five different antiretroviral drugs two HAARTFDC and three single drugs and the subsequent incubation with the blood samples collected from ten blood samples of HIV negative persons for the absorbance measurement using a digital Ultraviolet Visible MetaSpecAE1405031Pro Spectrophotometer. Reflectance Dielectric constant etc were derived from the absorbance data. For these drugs to be effective as HIV blockers they should be able to coat the surfaces of the lymphocytes. The question therefore arises as to what extent these drugs are able to coat the surfaces of the blood cells This was established using the extent of absorbance change. Models for coating effectiveness were formulated. The coating effectiveness was therefore calculated from peak absorbance values. Red blood cells were shown not to give reliable results. The results obtained however establish the fact that some coating of the drug had really occurred on the surfaces of the lymphocytes. The drug films were determined for lymphocytes and used to explain some observed clinical findings. The use of the findings of this work in drug design may be expected to yield good results.

  19. Predictors of mortality among HIV infected patients taking antiretroviral treatment in Ethiopia: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Biadgilign Sibhatu

    2012-05-01

    Full Text Available Abstract Background Studies indicate that there is high early mortality among patients starting antiretroviral treatment in sub-Saharan Africa. However, there is paucity of evidence on long term survival of patients on anti-retroviral treatment in the region. The objective of this study is to examine mortality and its predictors among a cohort of HIV infected patients on anti-retroviral treatment retrospectively followed for five years. Methods A retrospective cohort study was conducted among HIV infected patients on ART in eastern Ethiopia. Cox regression and Kaplan-Meier analyses were performed to investigate factors that influence time to death and survival over time. Result A total of 1540 study participants were included in the study. From the registered patients in the cohort, the outcome of patients as active, deceased, lost to follow up and transfer out was 1005 (67.2%, 86 (5.9%, 210 (14.0% and 192 (12.8% respectively. The overall mortality rate provides an incidence density of 2.03 deaths per 100 person years (95% CI 1.64 - 2.50. Out of a total of 86 deaths over 60 month period; 63 (73.3% died during the first 12 months, 10 (11.6% during the second year, and 10 (11.6% in the third year of follow up. In multivariate analysis, the independent predictors for mortality were loss of more 10% weight loss, bedridden functional status at baseline, ≤ 200 CD4 cell count/ml, and advanced WHO stage patients. Conclusion A lower level of mortality was detected among the cohort of patients on antiretroviral treatment in eastern Ethiopia. Previous history of weight loss, bedridden functional status at baseline, low CD4 cell count and advanced WHO status patients had a higher risk of death. Early initiation of ART, provision of nutritional support and strengthening of the food by prescription initiative, and counseling of patients for early presentation to treatment is recommended.

  20. Potential drug interactions in patients given antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Wendel Mombaque dos Santos

    Full Text Available ABSTRACT Objective: to investigate potential drug-drug interactions (PDDI in patients with HIV infection on antiretroviral therapy. Methods: a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r. Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. Results: of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000 and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p < 0.00. The clinical impact was prevalent sedation and cardiotoxicity. Conclusions: the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs.

  1. Pharmacokinetics and drug-drug interactions of antiretrovirals: an update.

    Science.gov (United States)

    Dickinson, Laura; Khoo, Saye; Back, David

    2010-01-01

    Current antiretroviral treatment has allowed HIV infection to become a chronic manageable condition with many HIV patients living longer. However, available antiretrovirals are not without limitations, for example the development of resistance and adverse effects. Consequently, new drugs in existing and novel classes are urgently required to provide viable treatment options to patients with few remaining choices. Darunavir, etravirine, maraviroc and raltegravir have been recently approved for treatment-experienced patients and other agents such as rilpivirine, vicriviroc and elvitegravir are currently under phase III study. Clinical studies are necessary to optimise potential treatment combinations and to manage drug-drug interactions to help avoid toxicity or therapy failure. This review aims to summarise the pharmacokinetics and key drug-drug interaction studies for newly available antiretrovirals and those in development. Further information regarding drug-drug interactions of well established antiretrovirals and those recently approved are readily available online at sites such as http://www.hiv-druginteractions.org, http://www.clinicaloptions.com/hiv, http://hivinsite.ucsf.edu. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.

  2. Long-term kinetics of T cell production in HIV-infected subjects treated with highly active antiretroviral therapy

    Science.gov (United States)

    Fleury, S.; Rizzardi, G. P.; Chapuis, A.; Tambussi, G.; Knabenhans, C.; Simeoni, E.; Meuwly, J.-Y.; Corpataux, J.-M.; Lazzarin, A.; Miedema, F.; Pantaleo, G.

    2000-01-01

    The long-term kinetics of T cell production following highly active antiretroviral therapy (HAART) were investigated in blood and lymph node in a group of HIV-infected subjects at early stage of established infection and prospectively studied for 72 wk. Before HAART, CD4 and CD8 T cell turnover was increased. However, the total number of proliferating CD4+ T lymphocytes, i.e., CD4+Ki67+ T lymphocytes, was not significantly different in HIV-infected (n = 73) and HIV-negative (n = 15) subjects, whereas proliferating CD8+Ki67+ T lymphocytes were significantly higher in HIV-infected subjects. After HAART, the total body number of proliferating CD4+Ki67+ T lymphocytes increased over time and was associated with an increase of both naive and memory CD4+ T cells. The maximal increase (2-fold) was observed at week 36, whereas at week 72 the number of proliferating CD4+ T cells dropped to baseline levels, i.e., before HAART. The kinetics of the fraction of proliferating CD4 and CD8 T cells were significantly correlated with the changes in the total body number of these T cell subsets. These results demonstrate a direct relationship between ex vivo measures of T cell production and quantitative changes in total body T lymphocyte populations. This study provides advances in the delineation of the kinetics of T cell production in HIV infection in the presence and/or in the absence of HAART. PMID:10805798

  3. Predictive factors of antiretroviral treatment French Guiana.

    Science.gov (United States)

    Elenga, Narcisse; Hanf, Matthieu; Nacher, Mathieu

    2012-01-01

    French Guiana is the French territory where the HIV epidemic is most preoccupying. In Cayenne, the mother to child HIV transmission rate was 6% in 2006-2008. Despite free testing and treatment, HIV pregnant women often have delayed or insufficient access to care. The aim of this study was to identify predictive factors of antiretroviral treatmentFrench Guiana) and then to describe their attitudes, practices, and beliefs regarding HIV/AIDS. A case control study was conducted including all deliveries in Cayenne from 2003 to 2010. For each case, a standardized questionnaire including epidemiological, clinical, and biological data was administered. The analysis first described the summary statistics and then bivariate analysis studied the relation of each variable with the outcome. Multivariate analysis adjusted for the confounding factors. Thirty-three women in the first group and 96 in the control group were included in the study. Women born in French Guiana (OR = 5, IC95% = 1.22-20.86, p=0.027) had a high risk of treatment<4 weeks. The other factors associated with treatment<4 weeks in our study were benefiting from food parcels (OR = 12.72, IC95% = 2.07-78.14, p=0.006), consulting a traditional healer when sick (OR = 9.86, IC95% = 2.57-37.88, p= < 0.001), and drug use (OR = 6.27, IC95% = 1.26-31.13, p=0.025). These predictive factors should be considered in prevention programs against mother to child transmission of HIV.

  4. Pharmacokinetic targets of antiretroviral therapy in children and adolescents

    Directory of Open Access Journals (Sweden)

    Michael N. Neely

    2013-06-01

    Full Text Available Large populations of HIV-infected and exposed infants, children and adolescents are increasingly exposed to antiretroviral therapy throughout dramatic changes of the body composition and maturation process in utero, perinatally and during the later growth and development throughout childhood and puberty. The majority of HIV-infected children live in the resource-limited setting where the presence of other significant co-morbidities such as malnutrition, tuberculosis and malaria complicates the selection of the most effective, safe and least toxic combination of antiretroviral drug therapy. This review focuses on the role of the pharmacokinetic factors including clinically important drug-drug interactions on the therapeutic targets of antiretroviral therapy throughout childhood and adolescence. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  5. The Place of protease inhibitors in antiretroviral treatment

    Directory of Open Access Journals (Sweden)

    S.B. Tenore

    2009-10-01

    Full Text Available With the introduction of highly active antiretroviral therapy, a number of drugs have been developed. The best choice concerning which antiretroviral analogs to start is always under discussion, especially in the choice between non-nucleoside reverse transcriptase inhibitors-based therapies and ritonavir-boosted protease inhibitors. Both are proven to control viral replication and lead to immunological gain. The choice between a non-nucleoside analog reverse transcriptase inhibitor and a protease inhibitor as a third antiretroviral drug in the therapy should consider factors related to the individual, as well as the inclusion of the best therapy in the patient's daily activities and potential adherence. The protease inhibitor-based therapies showed similar efficacy among the various inhibitors with characteristics concerning the adverse events from each medicine. For the treatment of protease-resistant patients, darunavir and tipranavir showed good efficacy with higher genetic barrier to resistance.

  6. Forgiveness of non-adherence to HIV-1 antiretroviral therapy.

    Science.gov (United States)

    Shuter, Jonathan

    2008-04-01

    Superior adherence to HIV-1 antiretroviral therapy is a mainstay of successful HIV management. Studies performed in the early era of highly active antiretroviral therapy demonstrated the need for > or =95% adherence in order to achieve and sustain viral suppression. High rates of viral suppression have been observed at more moderate levels of adherence with newer antiretroviral regimens. The term 'forgiveness' is being used to describe the ability of a regimen to achieve and sustain viral suppression, despite suboptimal adherence. A variety of pharmacological, viral and host properties determine the level of forgiveness of any specific regimen. As the choice of treatment options continues to expand, forgiveness of non-adherence is likely to emerge as an increasingly important factor in therapeutic decision-making.

  7. The (political) economics of antiretroviral treatment in developing countries.

    Science.gov (United States)

    Nattrass, Nicoli J

    2008-12-01

    Despite unprecedented international mobilisation to support universal provision of highly active antiretroviral therapy (HAART), national governments continue to play the key role in determining access to treatment. Whereas some AIDS-affected countries have performed as well as or better than expected given their level of development, institutional characteristics and demographic challenges (e.g. Thailand and Brazil), others (notably South Africa) have not. This article argues that the 'economics' of antiretroviral drug delivery is at heart a political-economy of access to treatment. It depends on commitment on the part of national governments to negotiate with pharmaceutical companies over patented antiretroviral drug prices, on their policy towards compulsory licensing, and on the approach they adopt to delivering HAART. Civil society has an important role to play in encouraging governments to become, and remain, committed to taking action to ensure sustainable and widespread access to HAART.

  8. Future implications: Compliance and failure with antiretroviral treatment

    Directory of Open Access Journals (Sweden)

    Patel Atul

    2006-01-01

    Full Text Available HIV management is currently in an era of effective, potent antiretroviral therapy. Modern drug discovery and development have transformed HIV-1 disease into a treatable, chronic infectious disease. Complete suppression of viral replication is critical for long-term durability of antiretroviral therapy. Partial suppression, even at very low levels, is likely to lead to virologic failure and ultimately to the appearance of drug resistance. The relationship between adherence and resistance to HIV antiretroviral therapy is more complex than to state ′non-adherence increases the risk of drug resistance.′ In many patients who fail to respond to initial therapy, the primary reason for failure is their inability to take the prescribed drug regimen or nonadherence.

  9. Associations between vascular co-morbidities and depression in insulin-naive diabetes patients

    DEFF Research Database (Denmark)

    Koopmans, B; Pouwer, F; de Bie, Rob A;

    2009-01-01

    AIMS/HYPOTHESIS: The aim of the study was to determine the prevalence of depression in insulin-naive diabetes patients and to investigate the associations between different forms of vascular co-morbidity and depression. METHODS: Cross-sectional data were used from a primary-care sample of 1......,269 insulin-naive (i.e. not using insulin therapy) diabetes patients participating in the DIAZOB Primary Care Diabetes study. Demographics, vascular co-morbidities, clinical and lifestyle characteristics, and psychosocial factors were assessed. Depression symptoms were measured with the Edinburgh Depression...... Scale, with a score >11 defined as depression. The chi (2) and Student's t tests were used to compare groups with and without vascular co-morbidities. Rates and odds ratios of depression were calculated for each vascular co-morbidity, with diabetes only as the reference group, correcting for age and sex...

  10. Modeling Spammer Behavior: Na\\"ive Bayes vs. Artificial Neural Networks

    CERN Document Server

    Islam, Md Saiful; Farhan, Khalid; Rahman, Md Abdur; Rahman, Joy

    2010-01-01

    Addressing the problem of spam emails in the Internet, this paper presents a comparative study on Na\\"ive Bayes and Artificial Neural Networks (ANN) based modeling of spammer behavior. Keyword-based spam email filtering techniques fall short to model spammer behavior as the spammer constantly changes tactics to circumvent these filters. The evasive tactics that the spammer uses are themselves patterns that can be modeled to combat spam. It has been observed that both Na\\"ive Bayes and ANN are best suitable for modeling spammer common patterns. Experimental results demonstrate that both of them achieve a promising detection rate of around 92%, which is considerably an improvement of performance compared to the keyword-based contemporary filtering approaches.

  11. Na\\"ive Physics and Quantum Mechanics: The Cognitive Bias of Everett's Many-Worlds Interpretation

    CERN Document Server

    Lang, Andrew Sid

    2016-01-01

    We discuss the role that intuitive theories of physics play in the interpretation of quantum mechanics. We compare and contrast na\\"ive physics with quantum mechanics and argue that quantum mechanics is not just hard to understand but that it is difficult to believe, often appearing magical in nature. Quantum mechanics is often discussed in the context of "quantum weirdness" and quantum entanglement is known as "spooky action at a distance." This spookiness is more than just because quantum mechanics doesn't match everyday experience; it ruffles the feathers of our na\\"ive physics cognitive module. In Everett's many-worlds interpretation of quantum mechanics, we preserve a form of deterministic thinking that can alleviate some of the perceived weirdness inherent in other interpretations of quantum mechanics, at the cost of having the universe split into parallel worlds at every quantum measurement. By examining the role cognitive modules play in interpreting quantum mechanics, we conclude that the many-worlds...

  12. System Dynamics Modelling of the Processes Involving the Maintenance of the Naive T Cell Repertoire

    CERN Document Server

    Figueredo, Grazziela P; Whitbrook, Amanda

    2010-01-01

    The study of immune system aging, i.e. immunosenescence, is a relatively new research topic. It deals with understanding the processes of immunodegradation that indicate signs of functionality loss possibly leading to death. Even though it is not possible to prevent immunosenescence, there is great benefit in comprehending its causes, which may help to reverse some of the damage done and thus improve life expectancy. One of the main factors influencing the process of immunosenescence is the number and phenotypical variety of naive T cells in an individual. This work presents a review of immunosenescence, proposes system dynamics modelling of the processes involving the maintenance of the naive T cell repertoire and presents some preliminary results.

  13. Naive and primed murine pluripotent stem cells have distinct miRNA expression profiles

    OpenAIRE

    Jouneau, A.; Ciaudo, C.; Sismeiro, O.; Brochard, V.; Jouneau, L.; Vandormael-Pournin, S; Coppee, J.-Y.; Zhou, Q.; Heard, E.; Antoniewski, C.; Cohen-Tannoudji, M.

    2012-01-01

    Over the last years, the microRNA (miRNA) pathway has emerged as a key component of the regulatory network of pluripotency. Although clearly distinct states of pluripotency have been described in vivo and ex vivo, differences in miRNA expression profiles associated with the developmental modulation of pluripotency have not been extensively studied. Here, the authors performed deep sequencing to profile miRNA expression in naive (embryonic stem cell [ESC]) and primed (epiblast stem cell [EpiSC...

  14. Are Prolactin Levels in Drug-Naive Schizophrenia Patients A Clinical Indicator?

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    Demet Yalcin

    2016-07-01

    Full Text Available Aim: The relationship between serum prolactin (PRL levels in patients with schizophrenia and the psychopathology, risk of relapse, symptom severity, the side effects after antipsychotics and schizophrenia subtypes are known. The aim of this study is to examine the serum PRL level difference between drug naive schizophrenia patients and healthy control group and between schizophrenia subtypes. Material and Method: 45 untreated volunteer participant between the ages of 18-55 who applied to Ankara Numune Training and Research Hospital, in patient and outpatient departments of Psychiatry, diagnosed with schizophrenia with the DSM IV-TR classification were included to study before getting treated. Participants were given sociodemographic information form; Axis-II for definitions Semi-Structured Clinical Interview, the Positive and Negative Syndrome Scale (PANSS and Global Assessment of Functioning Scale (GAF and biochemical measurements were made. Results: The mean serum PRL levels in drug naive patients with schizophrenia were higher compared to the control group (p = 0.004. When patients with schizophrenia divided in to two groups as “paranoid” and “non-paranoid”, the mean serum prolactin levels among these groups were significantly different (p = 0.000. There was no significant relationship between serum PRL levels and GAF scores (P = 0.116 or PANSS total scores (P = 0.676 in patients with drug naive schizophrenia. Discussion: The difference between mean serum PRL levels in drug naive schizophrenia patients and schizophrenia subtypes are consistent with studies in the literature. As to use PRL levels as a marker in the clinic, further studies are needed.

  15. Are Prolactin Levels in Drug-Naive Schizophrenia Patients A Clinical Indicator?

    OpenAIRE

    Demet Yalcin

    2016-01-01

    Aim: The relationship between serum prolactin (PRL) levels in patients with schizophrenia and the psychopathology, risk of relapse, symptom severity, the side effects after antipsychotics and schizophrenia subtypes are known. The aim of this study is to examine the serum PRL level difference between drug naive schizophrenia patients and healthy control group and between schizophrenia subtypes. Material and Method: 45 untreated volunteer participant between the ages of 18-55 who applied to Ank...

  16. Interleukin 7-engineered stromal cells: a new approach for hastening naive T cell recruitment.

    Science.gov (United States)

    Di Ianni, Mauro; Del Papa, Beatrice; De Ioanni, Maria; Terenzi, Adelmo; Sportoletti, Paolo; Moretti, Lorenzo; Falzetti, Franca; Gaozza, Eugenia; Zei, Tiziana; Spinozzi, Fabrizio; Bagnis, Claude; Mannoni, Patrice; Bonifacio, Elisabetta; Falini, Brunangelo; Martelli, Massimo F; Tabilio, Antonio

    2005-06-01

    In this study we determined whether human stromal cells could be engineered with a retroviral vector carrying the interleukin 7 (IL-7) gene and investigated the effects on T cells in vitro and in vivo in a murine model. Transduced mesenchymal cells strongly express CD90 (98.15%), CD105 (87.6%), and STRO-1 (86.7%). IL-7 production was 16.37 (+/-2 SD) pg/ml, which remained stable for 60 days. In vitro-immunoselected naive T cells maintained the CD45RA+ CD45RO- naive phenotype (4.2 times more than controls) after 7 days of culture with IL-7-engineered stromal cells. The apoptosis rate (4.7%) of the naive T cells cultured with transduced stromal cells overlapped with that of freshly isolated cells. Immunohistological analysis detected stromal cells in bone marrow, spleen, and thymus. Cotransplantation of IL-7-engineered stromal cells with CD34+ cells improved engraftment in terms of CD45+ cells and significantly increased the CD3+ cell count in peripheral blood, bone marrow, and spleen. These data demonstrate the following: (1) human stromal cells can be transduced, generating a normal layer; (2) transduced stromal cells in vitro maintain the naive T cell phenotype; and (3) IL-7-transduced stromal cells in vivo home to lymphoid organs and produce sufficient IL-7 in loco, supporting T cell development in a cotransplantation model. Because of their efficient cytokine production and homing, IL-7-engineered stromal cells might be an ideal vehicle to hasten immunological reconstitution in T cell-depleted hosts.

  17. Attenuation of morphine tolerance by minocycline and pentoxifylline in naive and neuropathic mice.

    Science.gov (United States)

    Mika, Joanna; Wawrzczak-Bargiela, Agnieszka; Osikowicz, Maria; Makuch, Wioletta; Przewlocka, Barbara

    2009-01-01

    We have previously demonstrated that glial inhibitors reduce the development of allodynia and hyperalgesia, potentiating the effect of a single morphine dose in a neuropathic pain model. This study explores the effects of two glial activation inhibitors, minocycline and pentoxifylline, on the development of tolerance to morphine in naive and chronic constriction injury (CCI)-exposed mice. Administration of morphine to naive (20 mg/kg; i.p.) and CCI-exposed mice (40 mg/kg; i.p.) twice daily resulted in tolerance to its anti-nociceptive effect after 6 days. Injections of morphine were combined with minocycline (30 mg/kg, i.p.) or pentoxifylline (20 mg/kg, i.p.) administered as two preemptive doses before first morphine administration in naive or pre-injury in CCI-exposed mice, and repeated twice daily 30 min before each morphine administration. With treatment, development of morphine tolerance was delayed by 5 days (from 6 to 11 days), as measured by the tail-flick test in naive and by tail-flick, von Frey, and cold plate tests in CCI-exposed mice. Western blot analysis of CD11b/c and GFAP protein demonstrated that minocycline and pentoxifylline, at doses delaying development of tolerance to morphine analgesia, significantly diminished the morphine-induced increase in CD11b/c protein level. We found that repeated systemic administration of glial inhibitors significantly delays development of morphine tolerance by attenuating the level of this microglial marker under normal and neuropathic pain conditions. Our results support the idea that targeting microglial activation during morphine therapy/treatment is a novel and clinically promising method for enhancing morphine's analgesic effects, especially in neuropathic pain.

  18. Diagnosis of combined faults in Rotary Machinery by Non-Naive Bayesian approach

    Science.gov (United States)

    Asr, Mahsa Yazdanian; Ettefagh, Mir Mohammad; Hassannejad, Reza; Razavi, Seyed Naser

    2017-02-01

    When combined faults happen in different parts of the rotating machines, their features are profoundly dependent. Experts are completely familiar with individuals faults characteristics and enough data are available from single faults but the problem arises, when the faults combined and the separation of characteristics becomes complex. Therefore, the experts cannot declare exact information about the symptoms of combined fault and its quality. In this paper to overcome this drawback, a novel method is proposed. The core idea of the method is about declaring combined fault without using combined fault features as training data set and just individual fault features are applied in training step. For this purpose, after data acquisition and resampling the obtained vibration signals, Empirical Mode Decomposition (EMD) is utilized to decompose multi component signals to Intrinsic Mode Functions (IMFs). With the use of correlation coefficient, proper IMFs for feature extraction are selected. In feature extraction step, Shannon energy entropy of IMFs was extracted as well as statistical features. It is obvious that most of extracted features are strongly dependent. To consider this matter, Non-Naive Bayesian Classifier (NNBC) is appointed, which release the fundamental assumption of Naive Bayesian, i.e., the independence among features. To demonstrate the superiority of NNBC, other counterpart methods, include Normal Naive Bayesian classifier, Kernel Naive Bayesian classifier and Back Propagation Neural Networks were applied and the classification results are compared. An experimental vibration signals, collected from automobile gearbox, were used to verify the effectiveness of the proposed method. During the classification process, only the features, related individually to healthy state, bearing failure and gear failures, were assigned for training the classifier. But, combined fault features (combined gear and bearing failures) were examined as test data. The achieved

  19. Antiretroviral therapy for prevention of HIV transmission: potential role for people who inject drugs in Central Asia.

    Science.gov (United States)

    McNairy, Margaret L; Deryabina, Anna; Hoos, David; El-Sadr, Wafaa M

    2013-11-01

    Interest in the use of antiretroviral therapy (ART) for prevention stems from mounting evidence from research studies demonstrating that ART is associated with a decrease in sexual HIV transmission among serodiscordant couples and, perhaps, in other populations at risk. There is paucity of data on the efficacy of ART for prevention in key populations, including persons who inject drugs (PWID). In this paper, we examine the current status of HIV services for PWID in Central Asia, the use of ART by this population and explore ART for prevention for PWID in this context. We also discuss research and implementation questions with relevance to such a strategy in the region.

  20. Clinical significance of increased cerebellar default-mode network connectivity in resting-state patients with drug-naive somatization disorder

    Science.gov (United States)

    Wang, Houliang; Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Li, Lehua; Zhao, Jingping

    2016-01-01

    Abstract The cerebellum has been proven to be connected to the brain network, as in the default-mode network (DMN), among healthy subjects and patients with psychiatric disorders. However, whether or not abnormal cerebellar DMN connectivity exists and what its clinical significance is among drug-naive patients with somatization disorder (SD) at rest remain unclear. A total of 25 drug-naive patients with SD and 28 healthy controls were enrolled for a resting-state scan. The imaging data were analyzed using the seed-based functional connectivity (FC) method. Compared with the controls, patients with SD showed increased left/right Crus I-left/right angular gyrus (AG) connectivity and Lobule IX-left superior medial prefrontal cortex (MPFC) connectivity. The FC values of the left/right Crus I-right AG connectivity of the patients were positively correlated with their scores in the somatization subscale of the symptom checklist-90 (Scl-90). A trend level of correlations was observed between the FC values of the left Crus I-left AG connectivity of the patients and their scores for the somatization subscale of Scl-90, as well as between the FC values of their Lobule IX-left superior MPFC connectivity and their scores for the Eysenck personality questionnaire (EPQ) extraversion. Our findings show the increased cerebellar DMN connectivity in patients with SD and therefore highlight the importance of the DMN in the neurobiology of SD. Increased cerebellar DMN connectivities are also correlated with their somatization severity and personality, both of which bear clinical significance. PMID:27428190

  1. In vivo assessment of antiretroviral therapy-associated side effects

    Directory of Open Access Journals (Sweden)

    Eduardo Milton Ramos-Sanchez

    2014-07-01

    Full Text Available Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.

  2. Antiretroviral activity of protease inhibitors against Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Lianet Monzote

    2013-02-01

    Full Text Available The introduction of highly active antiretroviral therapy (HAART has caused a marked reduction in the occurrence and severity of parasitic infections, including the toxoplasmic encephalitis (TE. These changes have been attributed to the restoration of cell-mediated immunity. This study was developed to examine the activity of six antiretroviral protease inhibitors (API on Toxoplasma gondii tachyzoites. The six API showed anti-Toxoplasma activity, with IC50 value between 1.4 and 6.6 µg/mL. Further studies at the molecular level should be performed to clarify if the use of API could be beneficial or not for AIDS patients with TE.

  3. Arrangement of Players Position in Soccer using the Technique of Naive Bayes

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    Gusti Made Trisetya Putra

    2015-12-01

    Full Text Available In the modern soccer era, soccer is already considered as an entertainment, even modern soccer already become as an industry or a business that considered can bring a great profit to the club owner. One of the most important factor in building a team is young age soccer player development. Right young age soccer player development method, can be very helpful in establish a good team. A professional team must have a coach, for the first team or junior team. The duties of a coach is determine a right position for soccer player in the game, this duties sometimes make a coach is hard to making a right decision. This research will discuss about how to design a decision support system for determine soccer player using naive bayes technique. Data mining used naive bayes technique for find a prediction for soccer player based on the player skill test result. From this research result, it can be seen that by using decision support system using data mining with naive bayes technique can be help coach performance in determine position for soccer player especially for young age soccer player development so that can help coach in the making right decision effectively and efficiently.

  4. Anorexic activity of cocaine and coca extract in naive and cocaine tolerant rats.

    Science.gov (United States)

    Vee, G L; Fink, G B; Constantine, G H

    1983-04-01

    Dose response curves for reducing limited access food consumption were determined for cocaine HCl IP, cocaine HCl PO, and whole Erythroxylum coca extract PO. The ED50's for cocaine HCl in drug naive rats were 19.6 mg/kg (IP) and 34.6 mg/kg (PO). When the dose of E. coca extract was expressed in terms of cocaine HCl content, the ED50 was 52.6 mg/kg (PO). When dose response curves were determined in rats that had received cocaine (45 mg/kg, PO) for 30 days, a shift to the right in the cocaine HCl curve (an ED50 of 98.4 mg/kg PO) indicated tolerance. However, the shift to the right was less for E. coca extract than for cocaine HCl. Although the anorexic activity of E. coca extract was less than that of an equivalent amount of cocaine in naive rats it was often more than that of equivalent doses of cocaine HCl in tolerant rats. Interaction with other constituents of E. coca extract appears to alter the potency of the cocaine content of the extract in different directions in naive and tolerant rats.

  5. Right lateralized white matter abnormalities in first-episode, drug-naive paranoid schizophrenia.

    Science.gov (United States)

    Guo, Wenbin; Liu, Feng; Liu, Zhening; Gao, Keming; Xiao, Changqing; Chen, Huafu; Zhao, Jingping

    2012-11-30

    Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia.

  6. Ensemble of Chaotic and Naive Approaches for Performance Enhancement in Video Encryption

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    Jeyamala Chandrasekaran

    2015-01-01

    Full Text Available Owing to the growth of high performance network technologies, multimedia applications over the Internet are increasing exponentially. Applications like video conferencing, video-on-demand, and pay-per-view depend upon encryption algorithms for providing confidentiality. Video communication is characterized by distinct features such as large volume, high redundancy between adjacent frames, video codec compliance, syntax compliance, and application specific requirements. Naive approaches for video encryption encrypt the entire video stream with conventional text based cryptographic algorithms. Although naive approaches are the most secure for video encryption, the computational cost associated with them is very high. This research work aims at enhancing the speed of naive approaches through chaos based S-box design. Chaotic equations are popularly known for randomness, extreme sensitivity to initial conditions, and ergodicity. The proposed methodology employs two-dimensional discrete Henon map for (i generation of dynamic and key-dependent S-box that could be integrated with symmetric algorithms like Blowfish and Data Encryption Standard (DES and (ii generation of one-time keys for simple substitution ciphers. The proposed design is tested for randomness, nonlinearity, avalanche effect, bit independence criterion, and key sensitivity. Experimental results confirm that chaos based S-box design and key generation significantly reduce the computational cost of video encryption with no compromise in security.

  7. Naive (commonsense) geography and geobrowser usability after ten years of Google Earth

    Science.gov (United States)

    Hamerlinck, J. D.

    2016-04-01

    In 1995, the concept of ‘naive geography’ was formally introduced as an area of cognitive geographic information science representing ‘the body of knowledge that people have about the surrounding geographic world’ and reflecting ‘the way people think and reason about geographic space and time, both consciously and subconsciously’. The need to incorporate such commonsense knowledge and reasoning into design of geospatial technologies was identified but faced challenges in formalizing these relationships and processes in software implementation. Ten years later, the Google Earth geobrowser was released, marking the beginning of a new era of open access to, and application of, geographic data and information in society. Fast-forward to today, and the opportunity presents itself to take stock of twenty years of naive geography and a decade of the ubiquitous virtual globe. This paper introduces an ongoing research effort to explore the integration of naive (or commonsense) geography concepts in the Google Earth geobrowser virtual globe and their possible impact on Google Earth's usability, utility, and usefulness. A multi-phase methodology is described, combining usability reviews and usability testing with use-case scenarios involving the U.S.-Canadian Yellowstone to Yukon Initiative. Initial progress on a usability review combining cognitive walkthroughs and heuristics evaluation is presented.

  8. Ensemble of Chaotic and Naive Approaches for Performance Enhancement in Video Encryption.

    Science.gov (United States)

    Chandrasekaran, Jeyamala; Thiruvengadam, S J

    2015-01-01

    Owing to the growth of high performance network technologies, multimedia applications over the Internet are increasing exponentially. Applications like video conferencing, video-on-demand, and pay-per-view depend upon encryption algorithms for providing confidentiality. Video communication is characterized by distinct features such as large volume, high redundancy between adjacent frames, video codec compliance, syntax compliance, and application specific requirements. Naive approaches for video encryption encrypt the entire video stream with conventional text based cryptographic algorithms. Although naive approaches are the most secure for video encryption, the computational cost associated with them is very high. This research work aims at enhancing the speed of naive approaches through chaos based S-box design. Chaotic equations are popularly known for randomness, extreme sensitivity to initial conditions, and ergodicity. The proposed methodology employs two-dimensional discrete Henon map for (i) generation of dynamic and key-dependent S-box that could be integrated with symmetric algorithms like Blowfish and Data Encryption Standard (DES) and (ii) generation of one-time keys for simple substitution ciphers. The proposed design is tested for randomness, nonlinearity, avalanche effect, bit independence criterion, and key sensitivity. Experimental results confirm that chaos based S-box design and key generation significantly reduce the computational cost of video encryption with no compromise in security.

  9. The BMP Pathway Participates in Human Naive CD4+ T Cell Activation and Homeostasis.

    Directory of Open Access Journals (Sweden)

    Víctor G Martínez

    Full Text Available Bone Morphogenetic Proteins (BMPs form a group of secreted factors that belongs to the TGF-β superfamily. Among different roles in a number of immune cell types, BMPs are known to regulate T cell development within the thymus, although the role of BMP signaling in human mature T cells remains elusive. In this study, we demonstrate that canonical BMP signaling is necessary during two critical events that regulate the size and function of human naive CD4+ T cell population: activation and homeostasis. Upon stimulation via TCR, naive CD4+ T cells upregulate the expression of BMP ligands triggering canonical BMP signaling in CD25+ cells. Blockade of BMP signaling severely impairs CD4+ T cell proliferation after activation mainly through regulation of IL-2, since the addition of this cytokine recuperates normal T cell expansion after inhibition of BMP signaling. Similarly, activation of canonical BMP pathway is required for both the maintenance of cell survival and the homeostatic proliferation induced by IL-7, a key factor for T cell homeostasis. Moreover, upregulation of two critical receptors for T cell homeostasis, CXCR4 and CCR9, triggered by IL-7 is also abrogated in the absence of BMP signaling. Collectively, we describe important roles of the canonical BMP signaling in human naive CD4+ T cell activation and homeostasis that could be valuable for clinical application.

  10. Epigenomic comparison reveals activation of "seed" enhancers during transition from naive to primed pluripotency.

    Science.gov (United States)

    Factor, Daniel C; Corradin, Olivia; Zentner, Gabriel E; Saiakhova, Alina; Song, Lingyun; Chenoweth, Josh G; McKay, Ronald D; Crawford, Gregory E; Scacheri, Peter C; Tesar, Paul J

    2014-06-05

    Naive mouse embryonic stem cells (mESCs) and primed epiblast stem cells (mEpiSCs) represent successive snapshots of pluripotency during embryogenesis. Using transcriptomic and epigenomic mapping we show that a small fraction of transcripts are differentially expressed between mESCs and mEpiSCs and that these genes show expected changes in chromatin at their promoters and enhancers. Unexpectedly, the cis-regulatory circuitry of genes that are expressed at identical levels between these cell states also differs dramatically. In mESCs, these genes are associated with dominant proximal enhancers and dormant distal enhancers, which we term seed enhancers. In mEpiSCs, the naive-dominant enhancers are lost, and the seed enhancers take up primary transcriptional control. Seed enhancers have increased sequence conservation and show preferential usage in downstream somatic tissues, often expanding into super enhancers. We propose that seed enhancers ensure proper enhancer utilization and transcriptional fidelity as mammalian cells transition from naive pluripotency to a somatic regulatory program.

  11. Evaluation of the impact of chitosan/DNA nanoparticles on the differentiation of human naive CD4+ T cells

    Science.gov (United States)

    Liu, Lanxia; Bai, Yuanyuan; Zhu, Dunwan; Song, Liping; Wang, Hai; Dong, Xia; Zhang, Hailing; Leng, Xigang

    2011-06-01

    Chitosan (CS) is one of the most widely studied polymers in non-viral gene delivery since it is a cationic polysaccharide that forms nanoparticles with DNA and hence protects the DNA against digestion by DNase. However, the impact of CS/DNA nanoparticle on the immune system still remains poorly understood. Previous investigations did not found CS/DNA nanoparticles had any significant impact on the function of human and murine macrophages. To date, little is known about the interaction between CS/DNA nanoparticles and naive CD4+ T cells. This study was designed to investigate whether CS/DNA nanoparticles affect the initial differentiation direction of human naive CD4+ T cells. The indirect impact of CS/DNA nanoparticles on naive CD4+ T cell differentiation was investigated by incubating the nanoparticles with human macrophage THP-1 cells in one chamber of a transwell co-incubation system, with the enriched human naive CD4+ T cells being placed in the other chamber of the transwell. The nanoparticles were also co-incubated with the naive CD4+ T cells to explore their direct impact on naive CD4+ T cell differentiation by measuring the release of IL-4 and IFN-γ from the cells. It was demonstrated that CS/DNA nanoparticles induced slightly elevated production of IL-12 by THP-1 cells, possibly owing to the presence of CpG motifs in the plasmid. However, this macrophage stimulating activity was much less significant as compared with lipopolysaccharide and did not impact on the differentiation of the naive CD4+ T cells. It was also demonstrated that, when directly exposed to the naive CD4+ T cells, the nanoparticles induced neither the activation of the naive CD4+ T cells in the absence of recombinant cytokines (recombinant human IL-4 or IFN-γ) that induce naive CD4+ T cell polarization, nor any changes in the differentiation direction of naive CD4+ T cells in the presence of the corresponding cytokines.

  12. Evaluation of the impact of chitosan/DNA nanoparticles on the differentiation of human naive CD4{sup +} T cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu Lanxia; Bai Yuanyuan; Zhu Dunwan; Song Liping; Wang Hai; Dong Xia; Zhang Hailing; Leng Xigang, E-mail: lengxg@bme.org.cn [Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Lab of Bioengineering, Institute of Biomedical Engineering (China)

    2011-06-15

    Chitosan (CS) is one of the most widely studied polymers in non-viral gene delivery since it is a cationic polysaccharide that forms nanoparticles with DNA and hence protects the DNA against digestion by DNase. However, the impact of CS/DNA nanoparticle on the immune system still remains poorly understood. Previous investigations did not found CS/DNA nanoparticles had any significant impact on the function of human and murine macrophages. To date, little is known about the interaction between CS/DNA nanoparticles and naive CD4{sup +} T cells. This study was designed to investigate whether CS/DNA nanoparticles affect the initial differentiation direction of human naive CD4{sup +} T cells. The indirect impact of CS/DNA nanoparticles on naive CD4{sup +} T cell differentiation was investigated by incubating the nanoparticles with human macrophage THP-1 cells in one chamber of a transwell co-incubation system, with the enriched human naive CD4{sup +} T cells being placed in the other chamber of the transwell. The nanoparticles were also co-incubated with the naive CD4{sup +} T cells to explore their direct impact on naive CD4{sup +} T cell differentiation by measuring the release of IL-4 and IFN-{gamma} from the cells. It was demonstrated that CS/DNA nanoparticles induced slightly elevated production of IL-12 by THP-1 cells, possibly owing to the presence of CpG motifs in the plasmid. However, this macrophage stimulating activity was much less significant as compared with lipopolysaccharide and did not impact on the differentiation of the naive CD4{sup +} T cells. It was also demonstrated that, when directly exposed to the naive CD4{sup +} T cells, the nanoparticles induced neither the activation of the naive CD4{sup +} T cells in the absence of recombinant cytokines (recombinant human IL-4 or IFN-{gamma}) that induce naive CD4{sup +} T cell polarization, nor any changes in the differentiation direction of naive CD4{sup +} T cells in the presence of the corresponding

  13. IL-7-Induced Proliferation of Human Naive CD4 T-Cells Relies on Continued Thymic Activity

    Science.gov (United States)

    Silva, Susana L.; Albuquerque, Adriana S.; Matoso, Paula; Charmeteau-de-Muylder, Bénédicte; Cheynier, Rémi; Ligeiro, Dário; Abecasis, Miguel; Anjos, Rui; Barata, João T.; Victorino, Rui M. M.; Sousa, Ana E.

    2017-01-01

    Naive CD4 T-cell maintenance is critical for immune competence. We investigated here the fine-tuning of homeostatic mechanisms of the naive compartment to counteract the loss of de novo CD4 T-cell generation. Adults thymectomized in early childhood during corrective cardiac surgery were grouped based on presence or absence of thymopoiesis and compared with age-matched controls. We found that the preservation of the CD31− subset was independent of the thymus and that its size is tightly controlled by peripheral mechanisms, including prolonged cell survival as attested by Bcl-2 levels. Conversely, a significant contraction of the CD31+ naive subset was observed in the absence of thymic activity. This was associated with impaired responses of purified naive CD4 T-cells to IL-7, namely, in vitro proliferation and upregulation of CD31 expression, which likely potentiated the decline in recent thymic emigrants. Additionally, we found no apparent constraint in the differentiation of naive cells into the memory compartment in individuals completely lacking thymic activity despite upregulation of DUSP6, a phosphatase associated with increased TCR threshold. Of note, thymectomized individuals featuring some degree of thymopoiesis were able to preserve the size and diversity of the naive CD4 compartment, further arguing against complete thymectomy in infancy. Overall, our data suggest that robust peripheral mechanisms ensure the homeostasis of CD31− naive CD4 pool and point to the requirement of continuous thymic activity to the maintenance of IL-7-driven homeostatic proliferation of CD31+ naive CD4 T-cells, which is essential to secure T-cell diversity throughout life. PMID:28154568

  14. French 2013 guidelines for antiretroviral therapy of HIV-1 infection in adults

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    Bruno Hoen

    2014-06-01

    Full Text Available Introduction: These guidelines are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the French health authorities in September 2013. The objective was to provide updated recommendations for antiretroviral treatment (ART of HIV-positive adults. Guidelines included the following topics: when to start, what to start, specific situations for the choice of the first session of antiretroviral therapy, optimization of antiretroviral therapy after virologic suppression, and management of virologic failure. Methods: Ten members of the French HIV 2013 expert group were responsible for guidelines on ART. They systematically reviewed the most recent literature. The chairman of the subgroup was responsible for drafting the guidelines, which were subsequently discussed within, and finalized by the whole expert group to obtain a consensus. Recommendations were graded for strength and level of evidence using predefined criteria. Economic considerations were part of the decision-making process for selecting preferred first-line options. Potential conflicts of interest were actively managed throughout the whole process. Results: ART should be initiated in any HIV-positive person, whatever his/her CD4 T-cell count, even when >500/mm3. The level of evidence of the individual benefit of ART in terms of mortality or progression to AIDS increases with decreasing CD4 cell count. Preferred initial regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine plus a non-nucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine, or a ritonavir-boosted protease inhibitor (atazanavir or darunavir. Raltegravir, lopinavir/r, and nevirapine are recommended as alternative third agents, with specific indications and restrictions. Specific situations such as HIV infection in women, primary HIV infection, severe immune suppression

  15. Maximizing the benefits of antiretroviral therapy for key affected populations

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    Ian R Grubb

    2014-07-01

    Full Text Available Introduction: Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART, and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion: Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions: Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including

  16. Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naïve HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwan

    Science.gov (United States)

    Wu, Pei-Ying; Cheng, Chien-Yu; Liu, Chun-Eng; Lee, Yi-Chien; Yang, Chia-Jui; Tsai, Mao-Song; Cheng, Shu-Hsing; Lin, Shih-Ping; Lin, De-Yu; Wang, Ning-Chi; Lee, Yi-Chieh; Sun, Hsin-Yun; Tang, Hung-Jen; Hung, Chien-Ching

    2017-01-01

    Objectives Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. Methods Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study. According to the national HIV treatment guidelines, patients were assessed at baseline, 2 and 4 weeks of cART initiation, and subsequently every 8 to 12 weeks. Plasma HIV RNA load, CD4 cell count and aminotransferases were determined. The toxicity grading scale of the Division of AIDS (DAIDS) 2014 was used for reporting clinical and laboratory adverse events. Results During the 3.5-year study period, 2,341 patients initiated nNRTI-containing cART: NVP in 629 patients, EFV 1,363 patients, and RPV 349 patients. Rash of any grade occurred in 14.1% (n = 331) of the patients. In multiple logistic regression analysis, baseline CD4 cell counts (per 100-cell/μl increase, adjusted odds ratio [AOR], 1.125; 95% confidence interval [95% CI], 1.031–1.228) and use of NVP (AOR, 2.443; 95% CI, 1.816–3.286) (compared with efavirenz) were independently associated with the development of skin rashes. Among the 1,455 patients (62.2%) with aminotransferase data both at baseline and week 4, 72 (4.9%) developed grade 2 or greater hepatotoxicity. In multiple logistic regression analysis, presence of antibody for hepatitis C virus (HCV) (AOR, 2.865; 95% CI, 1.439–5.704) or hepatitis B surface antigen (AOR, 2.397; 95% CI, 1.150–4.997), and development of skin rashes (AOR, 2.811; 95% CI, 1

  17. Effect of combination antiretroviral therapy on cytomegalovirus retinitis

    Directory of Open Access Journals (Sweden)

    Banker Alay

    2002-01-01

    Full Text Available Purpose: To study the various changes in the course of cytomegalovirus (CMV retinitis following combination antiretroviral treatment. Methods: Combination antiretroviral treatment was given to 12 patients with active CMV retinitis following which all anti-CMV medications were discontinued once the CD4 cell counts were> 100/mm3 for 3 months. Results: The median CD4 cell count increased from 36.5/mm3 (range, 3-74/mm3 at baseline to 175.5/mm3 (range, 97-410/mm3 at 3 months. No patient had reactivation of CMV retinitis or developed extraocular CMV infection during median follow-up of 16.7 months. In one patient with peripheral active CMV retinitis, the retinitis resolved completely and remained so throughout the follow-up period without specific anti-CMV treatment. Five (41.7% patients had immune recovery vitritis. Conclusion: Patients receiving combination antiretroviral treatment following treatment for CMV retinitis have better control of CMV retinitis but immune recovery vitritis is a common sequelae. Reactivation of CMV retinitis is common in patients who discontinue combination antiretroviral treatment

  18. Implementation and effectiveness of antiretroviral therapy in Greenland

    DEFF Research Database (Denmark)

    Lohse, N.; Ladefoged, K.; Obel, N.

    2008-01-01

    Analyses from the Danish HIV Cohort Study showed that, despite comparable economic means and general education of healthcare personnel, antiretroviral treatment of HIV in Greenland began later and has been implemented at a slower pace with lower therapeutic effectiveness than in Denmark. However...

  19. Combination antiretroviral therapy and the risk of myocardial infarction

    NARCIS (Netherlands)

    Friis-Moller, N; Sabin, CA; Weber, R; Monforte, AD; El-Sadr, WM; Reiss, P; Thiebaut, R; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Lundgren, JD; Lundgren, JD; Weber, R; Monteforte, AD; Bartsch, G; Reiss, P; Dabis, F; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Houyez, F; Loeliger, E; Tressler, R; Weller, I.; Friis-Moller, N; Sabin, CA; Sjol, A; Lundgren, JD; Sawitz, A; Rickenbach, M; Pezzotti, P; Krum, E; Meester, R; Lavignolle, V.; Sundstrom, A; Poll, B; Fontas, E; Torres, F; Petoumenos, K; Kjaer, J; Hammer, S; Neaton, J; Sjol, A; de Wolf, F; van der Ven, E; Zaheri, S; Van Valkengoed, L; Meester, R; Bronsveld, W; Weigel, H; Brinkman, K; Frissen, P; ten Veen, J; Hillbrand, M; Schieveld, S; Mulder, J; van Gorp, E; Meenhorst, P; Danner, S; Claessen, F; Perenboom, R; Schattenkerk, JKE; Godfried, M; Lange, J; Lowe, S; van der Meer, J; Nellen, F; Pogany, K; van der Poll, T; Reiss, R; Ruys, T; Wit, F; Richter, C; van Leusen, R; Vriesendorp, R; Jeurissen, F; Kauffmann, R; Koger, E; Brevenboer, B; Sprenger, HG; Law, G; ten Kate, RW; Leemhuis, M; Schippers, E; Schrey, G; van der Geest, S; Verbon, A; Koopmans, P; Keuter, M; Telgt, D; van der Ven, A; van der Ende, Marchina E.; Gyssens, I.; de Marie, S; Juttmann, J; van der Heul, C; Schneider, M; Borleffs, J; Hoepelman, I.; Jaspers, C; Matute, A; Schurink, C; Blok, W; Salamon, R; Beylot, J; Dupon, M; Le Bras, M; Pellegrin, JL; Ragnaud, JM; Dabis, F; Chene, G; Jacqmin-Gadda, H; Rhiebaut, R; Lawson-Ayayi, S; Lavignolle, V.; Balestre, E; Blaizeau, MJ; Decoin, M; Formaggio, AM; Delveaux, S; Labarerre, S; Uwamaliya, B; Vimard, E; Merchadou, L; Palmer, G; Touchard, D; Dutoit, D; Pereira, F; Boulant, B; Beylot, J; Morlat, P; Bonarek, M; Bonnet, F; Coadou, B; Gelie, P; Jaubert, D; Nouts, C; Lacoste, D; Dupon, M; Dutronc, H; Cipriano, G; Lafarie, S; Chossat, I.; Lacut, JY; Leng, B; Pellegrin, JL; Mercie, P; Viallard, JF; Faure, I.; Rispal, P; Cipriano, C; Tchamgoue, S; Le Bras, M; Djossou, F; Malvy, D; Pivetaud, JP; Ragnaud, JM; Chambon, D; De La Taille, C; Galperine, T; Lafarie, S; Neau, D; Ochoa, A; Beylot, C; Doutre, MS; Bezian, JH; Moreau, JF; Taupin, JL; Conri, C; Constans, J; Couzigou, P; Castera, L; Fleury, H; Lafon, ME; Masquelier, B; Pellegrin, I.; Trimoulet, P; Moreau, F; Mestre, C; Series, C; Taytard, A; Law, M; Petoumenos, K; Bal, J; Mijch, A; Watson, K; Roth, N; Wood, H; Austin, D; Gowers, A; Baker, B; McFarlane, R; Carr, A; Cooper, D; Chuah, J; Fankhauser, W; Mallal, S; Skett, J; Calvo, G; Torres, F; Mateau, S; Domingo, P; Sambeat, MA; Gatell, J; Del Cacho, E; Cadafalch, J; Fuster, M; Codina, C; Sirera, G; Vaque, A; Clumeck, N; De Wit, S; Gerard, M; Hildebrand, M; Kabeya, K; Konopnicki, D; Payen, MC; Poll, B; Van Laethem, Y; Neaton, J; Bartsch, G; El-Sadr, WM; Krum, E; Thompson, G; Wentworth, D; Luskin-Hawk, R; Telzak, E; El-Sadr, WM; Abrams, DI; Cohn, D; Markowitz, N; Arduino, R; Mushatt, D; Friedland, G; Perez, G; Tedaldi, E; Fisher, E; Gordin, F; Crane, LR; Sampson, J; Baxter, J; Kirk, O; Mocroft, A; Phillips, AN; Lundgren, JD; Vetter, N; Clumeck, N; Hermans, P; Colebunders, R; Machala, L; Nielsen, J; Benfield, T; Gerstoft, J; Katzenstein, T; Roge, B; Skinhoj, P; Pedersen, C; Katlama, C; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Miller, V.; Staszewski, S; Bieckel, M; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Karydis, I.; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, I.; Turner, D; Pollack, S; Ben-Ishai, Z; Bentwich, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, V.; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Finazzi, R; Monforte, VO; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, V.; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Boron-Kaczmarska, A; Pnyka, M; Beniowski, M; Trocha, H; Antunes, F; Mansinho, K; Proenca, R; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, V.; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Blaxhult, A; Heidemann, B; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Telenti, A; Hirschel, B; Soravia-Dunand, V.; Furrer, H; Fisher, M; Brettle, R; Barton, S; Johnson, AM; Mercey, D; Loveday, C; Johnson, MA; Pinching, A; Parkin, J; Weber, J; Scullard, G; Morfeldt, L; Thulin, G; Sunstrom, A; Akerlund, B; Koppel, K; Karlsson, A; Flamholc, L; Hakangard, C; Monforte, AD; Pezzotti, P; Moroni, M; Monforte, AD; Cargnel, A; Merli, S; Vigevani, GM; Pastecchia, C; Lazzarin, A; Novati, R; Caggese, L; Moioli, C; Mura, MS; Mannazzu, M; Suter, F; Arici, C; Manconi, PE; Piano, P; Mazzotta, F; Lo Caputo, S; Poggio, A; Bottari, G; Pagano, G; Alessandrini, A; Scasso, A; Vincenti, A; Abbadesse, V.; Mancuso, S; Alberici, F; Ruggieri, A; Arlotti, M; Ortolani, P; De Lalla, F; Tositti, G; Piersantelli, N; Piscopo, R; Raise, E; Pasquinucci, S; Soscia, F; Tacconi, L; Tirelli, U; Nasti, G; Santoro, D; Pusterla, L; Carosi, G; Castelli, F; Cadeo, G; Vangi, D; Carnevale, G; Galloni, D; Filice, G; Bruno, R; Sinicco, A; Sciandra, M; Caramello, P; Gennero, L; Soranzo, ML; Bonasso, M; Rizzardini, G; Migliorino, G; Chiodo, F; Colangeli, V.; Magnani, G; Ursitti, M; Menichetti, F; Martinelli, C; Esposito, R; Mussini, C; Ghinelli, F; Sighinolfi, L; Coronado, O; Zauli, T; Ballardini, G; Montroni, M; Zoli, A; Petrelli, E; Cioppi, A; Ortona, L; De Luca, A; Petrosillo, N; Noto, P; Narciso, P; Salcuni, P; Antinori, A; De Longis, P; Vullo, V.; Lichtner, M; Pastore, G; Minafra, G; Chiriann, A; Loiacono, L; Piazza, M; Nappa, S; Abrescia, N; De Marco, M; Colomba, A; Prestileo, T; De Stefano, C; La Gala, A; Ferraro, T; Scerbo, A; Grima, P; Tundo, P; Pizzigallo, E; D'Alessandro, M; Grisorio, B; Ferrara, S; Pradier, C; Fontas, E; Caissotti, C; Dellamonica, P; Bentz, L; Bernard, E; Chaillou, S; De Salvador-Guillouet, F; Durant, J; Guttman, R; Heripret, L; Mondain-Miton, V.; Perbost, I.; Prouvost-Keller, B; Pugliese, P; Rahelinirina, V.; Roger, PM; Vandenbos, F; Bernasconi, E; Bucher, H; Burgisser, P; Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Ten Napel, C.

    2003-01-01

    Background: It remains controversial whether exposure to combination antiretroviral treatment increases the risk of myocardial infarction. Methods: In this prospective observational study, we enrolled 23,468 patients from 11 previously established cohorts from December 1999 to April 2001 and collect

  20. Pharmacokinetics of antiretroviral therapy in HIV-1-infected children

    NARCIS (Netherlands)

    P.L.A. Fraaij (Pieter); J.J.A. van Kampen (Jeroen); D.M. Burger (David); R. de Groot (Ronald)

    2005-01-01

    textabstractThe initiation of antiretroviral therapy has resulted in an impressive reduction in the rate of disease progression in AIDS and HIV-1-related deaths in children; however, there are still several major challenges to be faced in order to improve therapy. A major topic that needs to be deal

  1. Generic antiretroviral drugs and HIV care: An economic review.

    Science.gov (United States)

    Yazdanpanah, Y; Schwarzinger, M

    2016-03-01

    The cost of HIV care in European countries is high. Direct medical costs, in France, have been estimated at 500,000 Euros per patient's lifetime (20,000 Euros/year/patient). Overall, 73% of these costs are related to antiretroviral treatments. In the current financial crisis context, some European countries are beginning to make economic decisions on the drugs to be used. These approaches are likely to become more frequent. It is obviously essential to prescribe the most effective, appropriate, best tolerated, and easy-to-use antiretroviral treatments to patients. However, while taking the above into consideration, and if various treatment options or combinations are available, cost should also be considered in the treatment choice. One may thus reflect on the use of generic antiretroviral agents as they have just been launched in France. We aimed to review the cost and cost-effectiveness of generic antiretroviral drugs and to review treatment strategies other than generic drugs that could help reduce HIV-related costs. HIV clinicians should consider treatment costs to avoid any future coercive measures.

  2. The emergence of drug resistant HIV variants and novel anti-retroviral therapy

    Institute of Scientific and Technical Information of China (English)

    Koosha Paydary; Parisa Khaghani; Sahra Emamzadeh-Fard; SeyedAhmad SeyedAlinaghi; Kazem Baesi

    2013-01-01

    After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world;however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint.

  3. Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.

    Directory of Open Access Journals (Sweden)

    Timothy B Hallett

    2011-11-01

    Full Text Available BACKGROUND: Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed. METHODS AND FINDINGS: We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is 70% effective. CONCLUSIONS: Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention. Please see later in the article for the Editors' Summary.

  4. Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.

    Science.gov (United States)

    Tittle, Victoria; Bull, Lauren; Boffito, Marta; Nwokolo, Nneka

    2015-01-01

    More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women

  5. Renal impairment in a rural African antiretroviral programme

    Directory of Open Access Journals (Sweden)

    Lessells Richard J

    2009-08-01

    Full Text Available Abstract Background There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods (i Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ≤ 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR of significantly impaired renal function (combining severe and moderate impairment. Co-variates for analysis were age, sex and CD4 count at initiation. Results (i There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8 whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5 with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/μl. In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1, male gender (aOR 1.89, 95% C.I. 1.39–2.56 and CD4 Conclusion In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited.

  6. Characteristics of HIV antiretroviral regimen and treatment adherence

    Directory of Open Access Journals (Sweden)

    Vera Lúcia da Silveira

    2003-06-01

    Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

  7. Risk of erectile dysfunction in transfusion-naive thalassemia men: a nationwide population-based retrospective cohort study.

    Science.gov (United States)

    Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

    2015-04-01

    Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction. This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities.

  8. Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction.

    Directory of Open Access Journals (Sweden)

    Reneé de Waal

    Full Text Available BACKGROUND: Lipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART. Both are assumed to be antiretroviral adverse drug reactions. METHODS: We conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals. RESULTS: Twenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs showed more limb fat loss (or less fat gain with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs; efavirenz (versus protease inhibitors (PIs; and NRTI-containing (versus NRTI-sparing. RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens. CONCLUSIONS: There is clear evidence of a causal relationship between NRTIs (especially thymidine analogues and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching.

  9. Subtrochanteric fractures in bisphosphonate-naive patients: results from the HORIZON-recurrent fracture trial.

    Science.gov (United States)

    Adachi, Jonathan D; Lyles, Kenneth; Boonen, Steven; Colón-Emeric, Cathleen; Hyldstrup, Lars; Nordsletten, Lars; Pieper, Carl; Recknor, Chris; Su, Guoqin; Bucci-Rechtweg, Christina; Magaziner, Jay

    2011-12-01

    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained incident subtrochanteric fractures with those sustaining other hip fractures. Subjects were bisphosphonate-naive or had a bisphosphonate washout period of 6-24 months and subsequently received an annual infusion of zoledronic acid 5 mg or placebo after low-trauma hip-fracture repair. In total, 2,127 men and women were included. Of the qualifying hip fractures, 5.2% were subtrochanteric, 54.8% femoral neck, 33.0% intertrochanteric, and 7.1% other (generally complex fractures of mixed type). Significant baseline (pre-hip fracture) differences were seen between index hip-fracture types, with the percentage of patients with extreme mobility problems being twofold higher in patients with index subtrochanteric fracture (9.9%) compared to other patients. The distribution of hip-fracture types was similar between the treatment groups at baseline. No patients with index subtrochanteric fractures and six patients with other qualifying hip fractures reported prior bisphosphonate use. Only one further subtrochanteric fracture occurred in each treatment group over an average 2-year patient follow-up. Subtrochanteric fractures are not uncommon in bisphosphonate-naive patients. Extreme difficulties with mobility may be a unique risk factor predisposing to development of incident subtrochanteric fractures rather than other types of hip fracture. In patients with recent hip fracture who received zoledronic acid therapy, the incidence of new subtrochanteric fractures was too small to draw any meaningful conclusions.

  10. Short term clinical disease progression in HIV-1 positive patients taking combination antiretroviral therapy : The EuroSIDA risk-score

    DEFF Research Database (Denmark)

    Mocroft, A; Ledergerber, B; Zilmer, K;

    2007-01-01

    (CI), 2.7-3.3]. Current levels of viral load, CD4 cell count, CD4 cell slope, anaemia, and body mass index all independently predicted new AIDS/death, as did age, exposure group, a prior AIDS diagnosis, prior antiretroviral treatment and stopping all antiretroviral drugs. The EuroSIDA risk......OBJECTIVES: To derive and validate a clinically applicable prognostic score for predicting short-term disease progression in HIV-infected patients taking combination antiretroviral therapy (cART). DESIGN AND METHODS: Poisson regression was used to identify prognostic markers for new AIDS....../death in patients taking cART. A score was derived for 4169 patients from EuroSIDA and validated on 5150 patients from the Swiss HIV Cohort Study (SHCS). RESULTS: In EuroSIDA, 658 events occurred during 22 321 person-years of follow-up: an incidence rate of 3.0/100 person-years of follow-up [95% confidence interval...

  11. A Naive Glance to Postmodern Architecture in 21st Century: Termination or Transformation?

    OpenAIRE

    Lerzan ARAS

    2015-01-01

    Too many years have past since Venturi’s Las Vegas analysis. Our taste, point of views, and of course our societal structure has changed. Gene Roddenberry’s cult TV series Star Trek which remained years on screen, turned out to be naive, and charming but also deficient for us. Communication channels have been increased. Technology’s rapid progress has surprised even itself. Lyotard’s analysis about postmodern conditions, or Hassan’s renewed descriptions about postmodernism should be moved to ...

  12. First-line antiretroviral drug discontinuations in children

    Science.gov (United States)

    Fortuin-de Smidt, Melony; de Waal, Reneé; Cohen, Karen; Technau, Karl-Günter; Stinson, Kathryn; Maartens, Gary; Boulle, Andrew; Igumbor, Ehimario U.; Davies, Mary-Ann

    2017-01-01

    Introduction There are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART) durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010. Methods We included children (<16 years at ART initiation) who initiated ≥3 antiretrovirals between 2004–2014 with ≥1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity. Results We included 3579 children with median follow-up duration of 41 months (IQR 14–72). At ART initiation, median age was 44 months (IQR 13–89) and median CD4 percent was 15% (IQR 9–21%). At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%), treatment failure (18%), treatment simplification (5%), drug interactions (3%), and other or unspecified reasons (18%). The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2–55.4), 1.6 (0.5–4.8), 2.0 (1.2–3.3), and 1.3 (0.6–2.8) per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively. Conclusions While stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health

  13. A model for extending antiretroviral care beyond the rural health centre

    Directory of Open Access Journals (Sweden)

    Wools-Kaloustian Kara K

    2009-09-01

    Full Text Available Abstract Background A major obstacle facing many lower-income countries in establishing and maintaining HIV treatment programmes is the scarcity of trained health care providers. To address this shortage, the World Health Organization has recommend task shifting to HIV-infected peers. Methods We designed a model of HIV care that utilizes HIV-infected patients, community care coordinators (CCCs, to care for their clinically stable peers with the assistance of preprogrammed personal digital assistants (PDAs. Rather than presenting for the standard of care, monthly clinic visits, in this model, patients were seen every three months in clinics and monthly by their CCCs in the community during the interim two months. This study was conducted in Kosirai Division, western Kenya, where eight of the 24 sub-locations (defined geographic areas within the division were randomly assigned to the intervention with the remainder used as controls. Prior to entering the field, CCCs underwent intensive didactic training and mentoring related to the assessment and support of HIV patients, as well as the use of PDAs. PDAs were programmed with specific questions and to issue alerts if responses fell outside of pre-established parameters. CCCs were regularly evaluated in six performance areas. An impressionistic analysis on the transcripts from the monthly group meetings that formed the basis of the continuous feedback and quality improvement programme was used to assess this model. Results All eight of the assigned CCCs successfully passed their training and mentoring, entered the field and remained active for the two years of the study. On evaluation of the CCCs, 89% of their summary scores were documented as superior during Year 1 and 94% as superior during Year 2. Six themes emerged from the impressionistic analysis in Year 1: confidentiality and "community" disclosure; roles and responsibilities; logistics; clinical care partnership; antiretroviral adherence; and

  14. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

    DEFF Research Database (Denmark)

    NN, NN; Mugavero, Michael J; May, Margaret

    2008-01-01

    OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between ...

  15. Opportunistic disease and mortality in patients coinfected with hepatitis B or C virus in the strategic management of antiretroviral therapy (SMART) study

    DEFF Research Database (Denmark)

    Tedaldi, Ellen; Peters, Lars; Neuhaus, Jacquie;

    2008-01-01

    with the viral suppression (continued use of antiretroviral therapy) group. We assessed whether participants with concurrent hepatitis had an increased risk of the end points evaluated in the SMART study. METHODS: Participants were classified as being positive for hepatitis B virus (HBV) if they had positive...... hepatitis B surface antigen results for >6 months and positive for HCV if they tested HCV antibody positive. The rate and hazard ratio (HR) of OD and/or death and its 2 components were compared by hepatitis status and drug conservation versus the viral suppression group. RESULTS: Among 5472 participants...... of antiretroviral therapy is particularly unsafe in persons with hepatitis virus coinfection. Although HCV- and/or HBV-coinfected participants constituted 17% of participants in the SMART study, almost one-half of all non-OD deaths occurred in this population. Viral hepatitis was an unlikely cause of this excess...

  16. Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy

    DEFF Research Database (Denmark)

    Kirk, Ole; Reiss, Peter; Uberti-Foppa, Caterina;

    2002-01-01

    maintenance therapy for cytomegalovirus (CMV) end-organ disease, disseminated Mycobacterium avium complex (MAC) infection, cerebral toxoplasmosis, and extrapulmonary cryptococcosis in patients receiving antiretroviral therapy. DESIGN: Observational study. SETTING: Seven European HIV cohorts. PATIENTS: 358...... identified: 162 for CMV disease, 103 for MAC infection, 75 for toxoplasmosis, and 39 for cryptococcosis. During 781 person-years of follow-up, five patients had relapse. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted when the CD4 lymphocyte....... One relapse (toxoplasmosis) was diagnosed after maintenance therapy interruption at a CD4 lymphocyte count greater than 200 x 10(6) cells/L for 15 months. The overall incidences of recurrent CMV disease, MAC infection, toxoplasmosis, and cryptococcosis were 0.54 per 100 person-years (95% CI, 0.07 to 1...

  17. TLR activation excludes circulating naive CD8+ T cells from gut-associated lymphoid organs in mice.

    Science.gov (United States)

    Heidegger, Simon; Kirchner, Sophie-Kathrin; Stephan, Nicolas; Bohn, Bernadette; Suhartha, Nina; Hotz, Christian; Anz, David; Sandholzer, Nadja; Stecher, Bärbel; Rüssmann, Holger; Endres, Stefan; Bourquin, Carole

    2013-05-15

    The trafficking of effector T cells is tightly regulated by the expression of site-specific sets of homing molecules. In contrast, naive T cells are generally assumed to express a uniform pattern of homing molecules and to follow a random distribution within the blood and secondary lymphoid organs. In this study, we demonstrate that systemic infection fundamentally modifies the trafficking of circulating naive CD8(+) T cells. We show that on naive CD8(+) T cells, the constitutive expression of the integrin α4β7 that effects their entry into GALT is downregulated following infection of mice with Salmonella typhimurium. We further show that this downregulation is dependent on TLR signaling, and that the TLR-activated naive CD8(+) T cells are blocked from entering GALT. This contrasts strongly with Ag-experienced effector T cells, for which TLR costimulation in the GALT potently upregulates α4β7 and enhances trafficking to intestinal tissues. Thus, TLR activation leads to opposite effects on migration of naive and effector CD8(+) T cells. Our data identify a mechanism that excludes noncognate CD8(+) T cells from selected immune compartments during TLR-induced systemic inflammation.

  18. Monitoring the initiation and kinetics of human dendritic cell-induced polarization of autologous naive CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Tammy Oth

    Full Text Available A crucial step in generating de novo immune responses is the polarization of naive cognate CD4+ T cells by pathogen-triggered dendritic cells (DC. In the human setting, standardized DC-dependent systems are lacking to study molecular events during the initiation of a naive CD4+ T cell response. We developed a TCR-restricted assay to compare different pathogen-triggered human DC for their capacities to instruct functional differentiation of autologous, naive CD4+ T cells. We demonstrated that this methodology can be applied to compare differently matured DC in terms of kinetics, direction, and magnitude of the naive CD4+ T cell response. Furthermore, we showed the applicability of this assay to study the T cell polarizing capacity of low-frequency blood-derived DC populations directly isolated ex vivo. This methodology for addressing APC-dependent instruction of naive CD4+ T cells in a human autologous setting will provide researchers with a valuable tool to gain more insight into molecular mechanisms occurring in the early phase of T cell polarization. In addition, it may also allow the study of pharmacological agents on DC-dependent T cell polarization in the human system.

  19. Combination of anti-retroviral drugs and radioimmunotherapy specifically kills infected cells from HIV infected individuals

    Directory of Open Access Journals (Sweden)

    Dina Tsukrov

    2016-09-01

    Full Text Available Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT, a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infect-ed cells. Since gp41 expression by infected cells is likely down-regulated in patients on an-tiretroviral therapy (ART, we evaluated the ability of RIT to kill ART-treated infected cells us-ing both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal anti-body to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. conjugated to the human monoclonal antibody 2556, which binds to HIV gp41. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: ten on ART and five ART-naive. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART, and supports continued development of 213Bi

  20. Risk of Cancer among Commercially Insured HIV-Infected Adults on Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Jeannette Y. Lee

    2016-01-01

    Full Text Available The objective of this study was to explore the cancer incidence rates among HIV-infected persons with commercial insurance who were on antiretroviral therapy and compare them with those rates in the general population. Paid health insurance claims for 63,221 individuals 18 years or older, with at least one claim with a diagnostic code for HIV and at least one filled prescription for an antiretroviral medication between January 1, 2006, and September 30, 2012, were obtained from the LifeLink® Health Plan Claims Database. The expected number of cancer cases in the general population for each gender-age group (60 years was estimated using incidence rates from the Surveillance Epidemiology and End Results (SEER program. Standardized incidence ratios (SIRs were estimated using their 95% confidence intervals (CIs. Compared to the general population, incidence rates for HIV-infected adults were elevated (SIR, 95% CI for Kaposi sarcoma (46.08; 38.74–48.94, non-Hodgkin lymphoma (4.22; 3.63–4.45, Hodgkin lymphoma (9.83; 7.45–10.84, and anal cancer (30.54; 25.62–32.46 and lower for colorectal cancer (0.69; 0.52–0.76, lung cancer (0.70; 0.54, 0.77, and prostate cancer (0.54; 0.45–0.58. Commercially insured, treated HIV-infected adults had elevated rates for infection-related cancers, but not for common non-AIDS defining cancers.

  1. Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a man with AIDS

    Directory of Open Access Journals (Sweden)

    Yoganathan K

    2012-04-01

    Full Text Available Katie Yoganathan1, David Brown2, Kathir Yoganathan31Cardiff Medical School, Cardiff, Wales, UK; 2Virus Reference Department, Microbiology Services, Health Protection Agency, London, UK; 3Singleton Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UKAbstract: A 43-year-old Caucasian homosexual man with AIDS presented with blurring of vision, change of personality, and memory loss in March 1999. He had first been admitted 2 months previously for treatment of Pneumocystis jiroveci pneumonia. A magnetic resonance imaging scan on admission showed multiple white matter lesions involving both subcortical cerebral hemispheres and cerebellar regions, with no mass effect or surrounding edema. JC virus was detected by nested polymerase chain reaction in the cerebrospinal fluid. These findings were diagnostic of progressive multifocal leukoencephalopathy (PML. His CD4 count was 34 cells/mL, and his HIV ribonucleic acid level was 800,789 copies/mL. He was treated with a combination antiretroviral therapy. He was last reviewed in October 2011. He was fully independent socially and mentally, but he still had some residual neurologic signs with right-sided homonymous hemianopia and visual agnosia. His HIV ribonucleic acid level was undetectable, and his CD4 count was 574 cells/mm3. Although the median survival of patients with PML was poor before the antiretroviral therapy era, our patient, who is now aged 55 years, is still alive 12 years after the diagnosis. The diagnosis of PML and differential diagnosis of focal neurologic signs in HIV-positive patients are discussed in this case report.Keywords: HIV, focal neurologic signs, cerebral toxoplasmosis, primary brain lymphoma, ischaemic stroke

  2. Epitope-Specific Vaccination Limits Clonal Expansion of Heterologous Naive T Cells during Viral Challenge

    Directory of Open Access Journals (Sweden)

    Lexus R. Johnson

    2016-10-01

    Full Text Available Despite robust secondary T cell expansion primed by vaccination, the impact on primary immune responses to heterotypic antigens remains undefined. Here we show that secondary expansion of epitope-specific memory CD8+ T cells primed by prior infection with recombinant pathogens limits the primary expansion of naive CD8+ T cells with specificity to new heterologous antigens, dampening protective immunity against subsequent pathogen challenge. The degree of naive T cell repression directly paralleled the magnitude of the recall response. Suppressed primary T cell priming reflects competition for antigen accessibility, since clonal expansion was not inhibited if the primary and secondary epitopes were expressed on different dendritic cells. Interestingly, robust recall responses did not impact antigen-specific NK cells, suggesting that adaptive and innate lymphocyte responses possess different activation requirements or occur in distinct anatomical locations. These findings have important implications in pathogen vaccination strategies that depend on the targeting of multiple T cell epitopes.

  3. DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis.

    Science.gov (United States)

    Filatova, Elena Nikolaevna; Anisenkova, Elena Viktorovna; Presnyakova, Nataliya Borisovna; Utkin, Oleg Vladimirovich

    2016-09-01

    Acute infectious mononucleosis (AIM) is a widespread viral disease that mostly affects children. Development of AIM is accompanied by a change in the ratio of immune cells. This is provided by means of different biological processes including the regulation of apoptosis of naive T-cells. One of the potential regulators of apoptosis of T-lymphocytes is a death receptor 3 (DR3). We have studied the role of DR3 in the regulation of apoptosis of naive CD4(+) (nTh) and CD8(+) (nCTL) T-cells in healthy children and children with AIM. In healthy children as well as in children with AIM, the activation of DR3 is accompanied by inhibition of apoptosis of nTh. In healthy children, the stimulation of DR3 resulted in the increase in apoptosis of nCTL. On the contrary, in children with AIM, the level of apoptosis of nCTL decreased after DR3 activation, which is a positive contribution to the antiviral immune response. In children with AIM, nCTL are characterized by reduced level of apoptosis as compared with healthy children. These results indicate that DR3 can be involved in the reduction of sensitivity of nCTL to apoptosis in children with AIM.

  4. Class of Antiretroviral Drugs and the Risk of Myocardial Infarction

    DEFF Research Database (Denmark)

    2007-01-01

    BACKGROUND: We have previously demonstrated an association between combination antiretroviral therapy and the risk of myocardial infarction. It is not clear whether this association differs according to the class of antiretroviral drugs. We conducted a study to investigate the association...... to the other drug class and established cardiovascular risk factors (excluding lipid levels), the relative rate of myocardial infarction per year of protease-inhibitor exposure was 1.16 (95% confidence interval [CI], 1.10 to 1.23), whereas the relative rate per year of exposure to nonnucleoside reverse......-transcriptase inhibitors was 1.05 (95% CI, 0.98 to 1.13). Adjustment for serum lipid levels further reduced the effect of exposure to each drug class to 1.10 (95% CI, 1.04 to 1.18) and 1.00 (95% CI, 0.93 to 1.09), respectively. CONCLUSIONS: Increased exposure to protease inhibitors is associated with an increased risk...

  5. The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties

    OpenAIRE

    Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C.; France, Charles P.; Dillon, Glenn H.; Forster, Michael J; Schetz, John A.

    2013-01-01

    Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indola...

  6. Predictive Utility of Brief AUDIT for HIV Antiretroviral Medication Nonadherence

    OpenAIRE

    Broyles, Lauren Matukaitis; Gordon, Adam J; Sereika, Susan M.; Ryan, Christopher M.; Erlen, Judith A.

    2011-01-01

    Alcohol use negatively affects adherence to antiretroviral therapy (ART), thus HIV/AIDS providers need accurate, efficient assessments of alcohol use. Using existing data from an efficacy trial of two cognitive-behavioral ART adherence interventions, we sought to determine if results on two common alcohol screening tests (Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) and its binge-related question (AUDIT-3)) predict ART nonadherence. Twenty seven percent of the sample (n=308...

  7. Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system.

    Science.gov (United States)

    Calcagno, Andrea; Di Perri, Giovanni; Bonora, Stefano

    2014-10-01

    HIV-positive patients may be effectively treated with highly active antiretroviral therapy and such a strategy is associated with striking immune recovery and viral load reduction to very low levels. Despite undeniable results, the central nervous system (CNS) is commonly affected during the course of HIV infection, with neurocognitive disorders being as prevalent as 20-50 % of treated subjects. This review discusses the pathophysiology of CNS infection by HIV and the barriers to efficacious control of such a mechanism, including the available data on compartmental drug penetration and on pharmacokinetic/pharmacodynamic relationships. In the reviewed articles, a high variability in drug transfer to the CNS is highlighted with several mechanisms as well as methodological issues potentially influencing the observed results. Nevirapine and zidovudine showed the highest cerebrospinal fluid (CSF) to plasma ratios, although target concentrations are currently unknown for the CNS. The use of the composite CSF concentration effectiveness score has been associated with better virological outcomes (lower HIV RNA) but has been inconsistently associated with neurocognitive outcomes. These findings support the CNS effectiveness of commonly used highly antiretroviral therapies. The use of antiretroviral drugs with increased CSF penetration and/or effectiveness in treating or preventing neurocognitive disorders however needs to be assessed in well-designed prospective studies.

  8. Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

    Directory of Open Access Journals (Sweden)

    Balkundi S

    2011-12-01

    Full Text Available Shantanu Balkundi1, Ari S Nowacek1, Ram S Veerubhotla1, Han Chen2, Andrea Martinez-Skinner1, Upal Roy1, R Lee Mosley1,3, Georgette Kanmogne1, Xinming Liu1,3,4, Alexander V Kabanov3,4, Tatiana Bronich3,4, JoEllyn McMillan1, Howard E Gendelman1,31Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA; 2Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA; 3Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USA; 4Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility.Keywords: human immunodeficiency virus type one, nanotoxicology, monocyte-derived macrophage, nanoformulated antiretroviral therapy, manufacturing techniques

  9. Care of Patients With HIV Infection: Antiretroviral Drug Regimens.

    Science.gov (United States)

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    The advent of combination antiretroviral drug regimens has transformed HIV infection from a fatal illness into a manageable chronic condition. All patients with HIV infection should be considered for antiretroviral therapy, regardless of CD4 count or HIV viral load, for individual benefit and to prevent HIV transmission. Antiretroviral drugs affect HIV in several ways: entry inhibitors block HIV entry into CD4 T cells; nucleotide and nucleoside reverse transcriptase inhibitors prevent reverse transcription from RNA to DNA via chain-terminating proteins; nonnucleoside reverse transcriptase inhibitors prevent reverse transcription through enzymatic inhibition; integrase strand transfer inhibitors block integration of viral DNA into cellular DNA; protease inhibitors block maturation and production of the virus. Current guidelines recommend six combination regimens for initial therapy. Five are based on tenofovir and emtricitabine; the other uses abacavir and lamivudine. Five include integrase strand transfer inhibitors. HIV specialists should assist with treating patients with complicated HIV infection, including patients with treatment-resistant HIV infection, coinfection with hepatitis B or C virus, pregnancy, childhood infections, severe opportunistic infections, complex drug interactions, significant drug toxicity, or comorbidities. Family physicians can treat most patients with HIV infection effectively by choosing appropriate treatment regimens, monitoring patients closely, and retaining patients in care.

  10. Transcription Factor Ets-2 Acts as a Preinduction Repressor of Interleukin-2 (IL-2) Transcription in Naive T Helper Lymphocytes.

    Science.gov (United States)

    Panagoulias, Ioannis; Georgakopoulos, Tassos; Aggeletopoulou, Ioanna; Agelopoulos, Marios; Thanos, Dimitris; Mouzaki, Athanasia

    2016-12-23

    IL-2 is the first cytokine produced when naive T helper (Th) cells are activated and differentiate into dividing pre-Th0 proliferating precursors. IL-2 expression is blocked in naive, but not activated or memory, Th cells by the transcription factor Ets-2 that binds to the antigen receptor response element (ARRE)-2 of the proximal IL-2 promoter. Ets-2 acts as an independent preinduction repressor in naive Th cells and does not interact physically with the transcription factor NFAT (nuclear factor of activated T-cells) that binds to the ARRE-2 in activated Th cells. In naive Th cells, Ets-2 mRNA expression, Ets-2 protein levels, and Ets-2 binding to ARRE-2 decrease upon cell activation followed by the concomitant expression of IL-2. Cyclosporine A stabilizes Ets-2 mRNA and protein when the cells are activated. Ets-2 silences directly constitutive or induced IL-2 expression through the ARRE-2. Conversely, Ets-2 silencing allows for constitutive IL-2 expression in unstimulated cells. Ets-2 binding to ARRE-2 in chromatin is stronger in naive compared with activated or memory Th cells; in the latter, Ets-2 participates in a change of the IL-2 promoter architecture, possibly to facilitate a quick response when the cells re-encounter antigen. We propose that Ets-2 expression and protein binding to the ARRE-2 of the IL-2 promoter are part of a strictly regulated process that results in a physiological transition of naive Th cells to Th0 cells upon antigenic stimulation. Malfunction of such a repression mechanism at the molecular level could lead to a disturbance of later events in Th cell plasticity, leading to autoimmune diseases or other pathological conditions.

  11. Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial

    DEFF Research Database (Denmark)

    El-Sadr, W M; Grund, B; Neuhaus, J;

    2008-01-01

    BACKGROUND: Episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. OBJECTIVE: To determine whether reinitiating continuous antiretroviral therapy in patients who received episodic treatment reduces excess risk for opportunistic disease ...

  12. Factors associated with adherence to antiretroviral therapy in HIV/AIDS patients: a cross-sectional study in Southern Brazil

    Directory of Open Access Journals (Sweden)

    C.A.T. Pinheiro

    2002-10-01

    Full Text Available A cross-sectional study was conducted on HIV-infected adults being treated with antiretroviral drugs at a reference service in Southern Brazil. Participants answered a sociodemographic questionnaire and were tested by scales assessing sociocognitive variables. Adherence to treatment was assessed by a self-report inventory developed for the study. Clinical information was obtained from the patients' records. Significance tests were conducted using univariate logistic regressions followed by multivariate logistic regression analysis. A total of 195 patients participated in the study and 56.9% of them reported > or = 95% adherence on the previous two days. In univariate analysis, the odds of adherence increased with self-efficacy (a person's conviction that he/she can successfully execute the behavior required to produce a certain desired outcome in taking medications as prescribed (OR = 3.50, 95% CI 1.90-6.55, and decreased with perception of negative affect and physical concerns (OR = 0.71, 95% CI 0.53-0.95. The odds were lower for taking antiretroviral medications >4 times a day (OR = 0.44, 95% CI 0.20-0.94 and higher for patients with 8 years of schooling (OR = 2.28, 95% CI 1.12-4.66. In the multivariate analysis, self-efficacy (OR = 3.33, 95% CI 1.69-6.56 and taking medication >4 times a day (OR = 0.34, 95% CI 0.14-0.80 were independently associated with adherence. Self-efficacy was the most important predictor of adherence, followed by number of times antiretroviral medication was taken per day. Among sociodemographic and clinical variables, only the number of years of schooling was associated with adherence. Motivational interventions based on self-efficacy may be useful for increasing treatment adherence.

  13. Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

    Science.gov (United States)

    Peluso, Michael J; Spudich, Serena

    2014-09-01

    The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

  14. Effector cells derived from naive T cells used in tumor immunotherapy of mice bearing B16 melanoma

    Institute of Scientific and Technical Information of China (English)

    Wen Ming; Xu Weili; Ren Lili; Gao Fei; Cui Naipeng; Wen Junye; Li Xinjiang

    2014-01-01

    Background Adoptive cell transfer (ACT) immunotherapy has been used clinically for years to treat malignancies.Improving the killing efficiency of effector cells,such as tumor-specific cytotoxic T lymphocytes (CTLs),is an important component for enhancing the clinical response of cancer immunotherapy.Hence,we explored a novel method for preparing cancer-specific CTLs using naive T lymphocytes.Methods C57BL/6 mice bearing B16 melanoma tumors were pretreated with cyclophosphamide (CTX) by peritoneal injection.The immunosuppressive influence of CTX on tumor regression and the tumor microenvironment was assessed.Naive T cells and T cell pools were isolated via negative selection using immunomagnetic beads.The proliferative potential and cytokine production of different T cell subpopulations were evaluated in vitro.Tumor-specific CTLs derived from naive T cells (naive CD4+ T cells:naive CD8+ T cells=2:1) and pooled T cells were generated in vitro,respectively.B16 melanoma-bearing C57BL/6 mice were pretreated with CTX,followed by ACT immunotherapy using dendritic cell-induced CTLs.The homing abilities of the effector cells and interleukin-2 (IL-2),interferon-y,granzyme B,and perforin mRNA levels in tumor tissues were evaluated,and the change in tumor volume was measured.Results Mice receiving CTX peritoneal pretreatment injections did not display tumor regression compared with control mice.However,a significant downregulation of splenic Tregs and tumor growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) serum levels was observed (P <0.05).Naive T cells showed a stronger proliferative capacity and elevated cytokine production than did pooled T cells (P <0.05).In addition,effector cells generated from naive T cells displayed more potent antitumor activity in vivo than those derived from pooled T cells (P <0.05).Conclusion Effector cells derived from the naive T cells possess a stronger proliferative potential,homing capacity,and enhanced cytokine production

  15. Clinical outcomes of first-line antiretroviral therapy in Latin America: analysis from the LATINA retrospective cohort study.

    Science.gov (United States)

    Angriman, Federico; Belloso, Waldo H; Sierra-Madero, Juan; Sánchez, Jorge; Moreira, Ronaldo Ismerio; Kovalevski, Leandro O; Orellana, Liliana C; Cardoso, Sandra Wagner; Crabtree-Ramirez, Brenda; La Rosa, Alberto; Losso, Marcelo H

    2016-02-01

    Nearly 2 million people are infected with human immunodeficiency virus (HIV) in Latin America. However, information regarding population-scale outcomes from a regional perspective is scarce. We aimed to describe the baseline characteristics and therapeutic outcomes of newly-treated individuals with HIV infection in Latin America. A Retrospective cohort study was undertaken. The primary explanatory variable was combination antiretroviral therapy based on either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The main outcome was defined as the composite of all-cause mortality and the occurrence of an AIDS-defining clinical event or a serious non-AIDS-defining event during the first year of therapy. The secondary outcomes included the time to a change in treatment strategy. All analyses were performed according to the intention to treat principle. A total of 937 treatment-naive patients from four participating countries were included (228 patients with PI therapy and 709 with NNRTI-based treatment). At the time of treatment initiation, the patients had a mean age of 37 (SD: 10) years and a median CD4 + T-cell count of 133 cells/mm(3) (interquartile range: 47.5-216.0). Patients receiving PI-based regimens had a significantly lower CD4 + count, a higher AIDS prevalence at baseline and a shorter time from HIV diagnosis until the initiation of treatment. There was no difference in the hazard ratio for the primary outcome between groups. The only covariates associated with the latter were CD4 + cell count at baseline, study site and age. The estimated hazard ratio for the time to a change in treatment (NNRTI vs PI) was 0.61 (95% CI 0.47-0.80, p Latin America present with similar clinical outcomes regardless of the choice of initial therapy. Patients treated with PIs are more likely to require a treatment change during the first year of follow up.

  16. Attenuated SIV causes persisting neuroinflammation in the absence of a chronic viral load and neurotoxic antiretroviral therapy

    Science.gov (United States)

    Ferguson, Deborah; Clarke, Sean; Berry, Neil; Almond, Neil

    2016-01-01

    Objectives: Using simian models, where SIV chronic viral loads are naturally controlled in the absence of potentially neurotoxic therapies, we investigated the neuropathological events occurring during times of suppressed viraemia and when these events were initiated. Design: Cynomolgus macaques were infected with SIV strains that are naturally controlled to low levels of chronic viraemia. Study 1: animals were maintained up to 300 days after inoculation and analysed for viral-induced neuropathology following sustained suppression of chronic viral loads. Study 2: initiation and development of lesion was examined following 3, 10, 21, or 125 days SIVmacC8 infection. Methods: Formalin-fixed, paraffin-embedded brain sections were analysed following immunohistochemical staining for simian immunodeficiency virus (SIV) (KK41), blood–brain barrier leakage (ZO-1, fibrinogen), apoptosis (active caspase 3), neuroinflammation [GFAP, cyclooxygenase (COX)-1, COX-2], microglia and macrophage (Iba-1, CD68, and CD16), oligodendrocytes (CNPase1), MHC class II expression, and T cells (CD3 and CD8). Replicating SIV was detected through in-situ hybridization. Results: Study 1: neuroinflammation was present despite prolonged suppressed viraemia. Study 2: attenuated SIV entered the brain rapidly triggering acute phase neuroinflammatory responses. These did not return to naive levels and GFAP and COX-2 responses continued to develop during a chronic phase with a suppressed viral load. Conclusion: Neuroinflammatory responses similar to those in HIV neurocognitively impaired patients are present within macaque brains during prolonged periods of suppressed SIV viral load and in the absence of potentially neurotoxic antiretroviral drugs. These responses, initiated during acute infection, do not resolve despite the lack of on-going peripheral viraemia to potentially reseed the brain. PMID:27258396

  17. Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Côte d’Ivoire

    Science.gov (United States)

    Kroidl, Arne; Ello, Frederic; Mgaya, Jimson; Lennemann, Tessa; Moh, Raoul; Maganga, Lucas; Eholie, Serge; Pruvost, Alain; Saathoff, Elmar; Girard, Pierre-Marie; Zuhse, Ralph; von Massow, Friedrich; Anglaret, Xavier; Hoelscher, Michael; Danel, Christine

    2017-01-01

    Objective: Use of zidovudine (ZDV) in antiretroviral therapy is limited by toxicity and twice daily (b.i.d.) dosing. Fozivudine (FZD) is a ZDV prodrug, which is activated intracellularly to ZDV-monophosphate especially in mononuclear cells but not in bone marrow cells. FZD promises improved myelotoxicity and once daily (o.d.) dosing. Design: Randomized clinical trial. Methods: We conducted an open-label, phase II, proof-of-concept trial investigating three different FZD doses (800 mg o.d., 600 mg b.i.d., 1200 mg o.d.) versus ZDV (300 mg b.i.d.) in combination with lamivudine and efavirenz in HIV-infected, ART-naive patients from Tanzania and Côte d’Ivoire. The primary objective was to demonstrate virological efficacy after 24 weeks in intent-to treat and per-protocol analysis. Secondary endpoints included safety and pharmacokinetic outcomes. Results: Of 119 participants included in the intent-to treat analysis, HIV RNA less than 50 copies/ml at 24 weeks was observed in 64 of 88 (73%) patients in the combined FZD arms versus 24 of 31 (77%) in the ZDV arm (RR 0.94, 95% confidence interval 0.75–1.18). In the per-protocol analysis, responses were 64 of 77 (87%) versus 23 of 29 (79%), respectively (RR 1.09, 95% confidence interval 0.89–1.34). Outcomes were similar between FZD arms. Overall, treatments were well tolerated. Severe or worse anaemia occurred in two cases (one related to FZD, one to ZDV), grade III/IV neutropenia was less frequent in FZD compared with ZDV arms (22 versus 42%, P = 0.035). Pharmacokinetic analysis supported o.d. administration of FZD. Conclusion: Virological 24-week efficacy was demonstrated in b.i.d. and o.d. administered FZD-based regimens. Reduced myelotoxicity of FZD needs to be confirmed in a larger trial. PMID:27941394

  18. Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naive and memory T-cell subsets.

    Directory of Open Access Journals (Sweden)

    Willard Tinago

    Full Text Available BACKGROUND: Although effective antiretroviral therapy(ART increases CD4+ T-cell count, responses to ART vary considerably and only a minority of patients normalise their CD4+/CD8+ ratio. Although retention of naïve CD4+ T-cells is thought to predict better immune responses, relationships between CD4+ and CD8+ T-cell subsets and CD4+/CD8+ ratio have not been well described. METHODS: A cross-sectional study in a cohort of ambulatory HIV+ patients. We used flow cytometry on fresh blood to determine expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+(central memory, CD45RO+CD62L-(effector memory and CD45RO-CD62L+(naïve alongside routine T-cell subsets(absolute, percentage CD4+ and CD8+ counts, HIVRNA and collected demographic and treatment data. Relationship between CD4+/CD8+ T-cell ratio and expanded T-cell subsets was determined using linear regression analysis. Results are median[IQR] and regression coefficients unless stated. RESULTS: We recruited 190 subjects, age 42(36-48 years, 65% male, 65.3% Caucasian, 91% on ART(52.6% on protease inhibitors, 78.4% with HIVRNA1. Of the expanded CD4+ T-cell subsets, 27.3(18.0-38.3% were naïve, 36.8(29.0-40.0% central memory and 27.4(20.0-38.5% effector memory. Of the CD8+ T-cells subsets, 16.5(10.2-25.5% were naïve, 19.9(12.7-26.6% central memory and 41.0(31.8-52.5% effector memory. In the multivariable adjusted analysis, total cumulative-ART exposure(+0.15,p = 0.007, higher nadir CD4+ count(+0.011,p1 had significantly higher median %CD8+ naive T-cells; 25.4(14.0-36.0% versus 14.4(9.4-21.6%, p<0.0001, but significantly lower absolute CD8+ count; 464(384.5-567 versus 765(603-1084 cells/mm3, p<0.001. CONCLUSIONS: Study suggests important role for naïve CD8+ T-cell populations in normalisation of the immune response to HIV-infection. How these findings relate to persistent immune activation on ART requires further study.

  19. Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.

    Science.gov (United States)

    Jordan, M R; Obeng-Aduasare, Y; Sheehan, H; Hong, S Y; Terrin, N; Duong, D V; Trung, N V; Wanke, C; Kinh, N V; Tang, A M

    2014-08-01

    The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9 ± 4.9 years. The median duration on antiretroviral therapy was 16.2 ± 12.7 months; 83% reported 'very good' or 'perfect' adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30-3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14-1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases.

  20. Persons Living with HIV/AIDS: Employment as a Social Determinant of Health

    Science.gov (United States)

    Hergenrather, Kenneth C.; Zeglin, Robert J.; Conyers, Liza; Misrok, Mark; Rhodes, Scott D.

    2016-01-01

    Purpose: For persons living with HIV/AIDS (PLWHA), the advent of highly active antiretroviral therapy has increased their longevity and quality of life. As HIV progresses, many PLWHA present declined domains of functioning that impede their ability to work. The authors explore employment as a social determinant of health to identify issues…

  1. Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

    Science.gov (United States)

    Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia

    2015-08-01

    SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy.

  2. Relation of an ability measure of emotional intelligence to personality.

    Science.gov (United States)

    Caruso, David R; Mayer, John D; Salovey, Peter

    2002-10-01

    Is emotional intelligence simply a naive theory of personality, or is it a form of intelligence? If emotional intelligence is to be of value, it must measure something unique and distinct from standard personality traits. To explore this question, this study examined an ability test of emotional intelligence and its relationship to personality test variables to determine the extent to which these constructs overlap. A sample of 183 men and women took the Multifactor Emotional Intelligence Scale (Mayer, Caruso, & Salovey, 1999), an ability measure of emotional intelligence as well as measures of career interests, personality, and social behavior. Emotional intelligence was measured reliably and was relatively independent of traditionally defined personality traits, supporting the discriminant validity of the emotional intelligence construct.

  3. Antiretroviral treatment switch strategies for lowering the costs of antiretroviral therapy in subjects with suppressed HIV-1 viremia in Spain

    Directory of Open Access Journals (Sweden)

    Llibre JM

    2013-05-01

    Full Text Available Josep M Llibre,1,2 Gloria Cardona,3 José R Santos,2 Angels Andreu,3 Josep O Estrada,4 Jordi Ara,4 Xavier Bonafont,3 Bonaventura Clotet1,21HIV Unit, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 2Lluita contra la SIDA Foundation, Badalona, Barcelona, Spain; 3Hospital Pharmacy, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 4Hospital Management, University Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainBackground: The current economic recession in European countries has forced governments to design emergency measures to reduce spending on drugs, including antiretroviral therapy (ART. Switching antiretroviral drugs for others that have the same efficacy and safety profile at a lower cost (cost-reduction measures, CRM could prove to be a valid means of generating savings.Methods: Descriptive study of prospective consensus-based CRM undertaken in 2011 in a Catalonian hospital HIV unit among patients with prolonged plasma HIV-1 RNA <50 copies/mL.Results: During the study period, we made 673 switches (87.5% more than the previous year, of which 378 (56.2% were CRM (16% of all patients treated, leading to a savings of €87,410/month. Switching tenofovir/emtricitabine for abacavir/lamivudine was the most common CRM (129, 31.3%, followed by simplification to boosted protease inhibitor monotherapy (bPImono, 102, 26%. The CRM that generated the greatest saving were switching to bPImono (38%, withdrawal or replacement of raltegravir (24%, switching tenofovir/emtricitabine for abacavir/lamivudine (13%, and switching to nevirapine (5%. Cost savings with CRM were slightly higher than those achieved with medication paid for by clinical trial sponsors (€80,333/month or through discount arrangements (€76,389/month.Conclusion: Proactively switching antiretroviral therapy in selected treated patients with sustained virological suppression can generate significant cost savings in pharmacy spending in

  4. Targeted Help for Spoken Dialogue Systems: Intelligent Feedback Improves Naive Users' Performance

    Science.gov (United States)

    Hockey, Beth Ann; Lemon, Oliver; Campana, Ellen; Hiatt, Laura; Aist, Gregory; Hieronymous, Jim; Gruenstein, Alexander; Dowding, John

    2003-01-01

    We present experimental evidence that providing naive users of a spoken dialogue system with immediate help messages related to their out-of-coverage utterances improves their success in using the system. A grammar-based recognizer and a Statistical Language Model (SLM) recognizer are run simultaneously. If the grammar-based recognizer suceeds, the less accurate SLM recognizer hypothesis is not used. When the grammar-based recognizer fails and the SLM recognizer produces a recognition hypothesis, this result is used by the Targeted Help agent to give the user feed-back on what was recognized, a diagnosis of what was problematic about the utterance, and a related in-coverage example. The in-coverage example is intended to encourage alignment between user inputs and the language model of the system. We report on controlled experiments on a spoken dialogue system for command and control of a simulated robotic helicopter.

  5. Text Classification using Association Rule with a Hybrid Concept of Naive Bayes Classifier and Genetic Algorithm

    CERN Document Server

    Kamruzzaman, S M; Hasan, Ahmed Ryadh

    2010-01-01

    Text classification is the automated assignment of natural language texts to predefined categories based on their content. Text classification is the primary requirement of text retrieval systems, which retrieve texts in response to a user query, and text understanding systems, which transform text in some way such as producing summaries, answering questions or extracting data. Now a day the demand of text classification is increasing tremendously. Keeping this demand into consideration, new and updated techniques are being developed for the purpose of automated text classification. This paper presents a new algorithm for text classification. Instead of using words, word relation i.e. association rules is used to derive feature set from pre-classified text documents. The concept of Naive Bayes Classifier is then used on derived features and finally a concept of Genetic Algorithm has been added for final classification. A system based on the proposed algorithm has been implemented and tested. The experimental ...

  6. Clinical role of obinutuzumab in the treatment of naive patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Cerquozzi, Sonia; Owen, Carolyn

    2015-01-01

    The introduction of targeted therapy against CD20(+) with the monoclonal antibody rituximab has dramatically improved the survival of B-cell non-Hodgkin lymphoma including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma. Unfortunately, CLL remains incurable with chemoimmunotherapy, with many patients having refractory or relapsing disease after rituximab-containing therapy. Obinutuzumab (GA101) is a novel humanized Type II anti-CD20 monoclonal antibody that has been investigated and compared to rituximab. Here, we provide an overview of obinutuzumab, including its mechanisms of action, preclinical data, and Phase I to III clinical studies. Preclinical data illustrate obinutuzumab's higher potency compared to rituximab through antibody-dependent cellular cytotoxicity and direct cell death. Recently, the CLL11 study presented a significant benefit from obinutuzumab chemoimmunotherapy and supports its use for treatment-naive unfit CLL patients. Herein, we review that obinutuzumab is both a safe and effective alternative to rituximab.

  7. Attenuated neural response to gamble outcomes in drug-naive patients with Parkinson’s disease

    DEFF Research Database (Denmark)

    van der Vegt, Joyce P M; Hulme, Oliver J; Zittel, Simone;

    2013-01-01

    Parkinson's disease results from the degeneration of dopaminergic neurons in the substantia nigra, manifesting as a spectrum of motor, cognitive and affective deficits. Parkinson's disease also affects reward processing, but disease-related deficits in reinforcement learning are thought to emerge...... at a slower pace than motor symptoms as the degeneration progresses from dorsal to ventral striatum. Dysfunctions in reward processing are difficult to study in Parkinson's disease as most patients have been treated with dopaminergic drugs, which sensitize reward responses in the ventral striatum, commonly...... resulting in impulse control disorders. To circumvent this treatment confound, we assayed the neural basis of reward processing in a group of newly diagnosed patients with Parkinson's disease that had never been treated with dopaminergic drugs. Thirteen drug-naive patients with Parkinson's disease and 12...

  8. Maternal CD4+ Cell Count Decline after Interruption of Antiretroviral Prophylaxis for the Prevention of Mother-to-Child Transmission of HIV

    Science.gov (United States)

    Ekouevi, Didier; Abrams, Elaine J.; Schlesinger, Malka; Myer, Landon; Phanuphak, Nittaya; Carter, Rosalind J.

    2012-01-01

    Background We evaluated maternal CD4+ cell count (CD4+) decline after PMTCT prophylaxis in a multi-country HIV care program. Methods Analysis was restricted to antiretroviral therapy (ART)-naive, HIV-infected pregnant women with CD4+ ≥250 cells/mm3 at enrollment. Single-dose nevirapine (sd-NVP) or short-course antiretroviral prophylaxis (sc-ARVp) with zidovudine (AZT) or AZT + lamivudine (3TC) was initiated in 11 programs while 2 programs offered triple-drug antiretroviral prophylaxis (tARVp) (AZT+3TC+ NVP or nelfinavir). All regimens were stopped at delivery. CD4+ decline was defined as proportion of women who declined to CD4+ <350 cells/mm3 or <200 cells/mm3 at 24 months. Weibull regression was used for multivariable analysis. Findings A total of 1,393 women with enrollment CD4+ ≥250 cells/mm3 initiated tARVp (172; 12%) or sc-ARVp (532; 38%) during pregnancy or received intrapartum sd-NVP (689; 50%). At enrollment, maternal median age was 27 years (interquartile range (IQR) 23–30), median CD4+ was 469 cells/mm3 (IQR: 363–613). At 24 months post-delivery, the cumulative probability of CD4+ decline to <200 cells/mm3 was 12% (95% CI: 10–14). Among a subgroup of 903 women with CD4+ ≥400 cells at enrollment, the 24 month cumulative probability of decline to CD4+ <350 cells/mm3 was 28%; (95% CI: 25–32). Lower antepartum CD4+ was associated with higher probability of CD4+ decline to <350 cells/mm3: 46% (CD4+400–499 cells/mm3) vs. 19% (CD4+ ≥500 cells/mm3). After adjusting for age, enrollment CD4+ and WHO stage, women who received tARVp or sd-NVP were twice as likely to experience CD4+ decline to <350 cells/mm3 within 24 months than women receiving sc-ARVp (adjusted hazard ratio: 2.2; 95% CI: 1.5–3.2, p<0.0001). Conclusion Decline in CD4+ cell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery. PMID:22952754

  9. Maternal CD4+ cell count decline after interruption of antiretroviral prophylaxis for the prevention of mother-to-child transmission of HIV.

    Directory of Open Access Journals (Sweden)

    Didier Ekouevi

    Full Text Available BACKGROUND: We evaluated maternal CD4+ cell count (CD4+ decline after PMTCT prophylaxis in a multi-country HIV care program. METHODS: Analysis was restricted to antiretroviral therapy (ART-naive, HIV-infected pregnant women with CD4+ ≥250 cells/mm(3 at enrollment. Single-dose nevirapine (sd-NVP or short-course antiretroviral prophylaxis (sc-ARVp with zidovudine (AZT or AZT + lamivudine (3TC was initiated in 11 programs while 2 programs offered triple-drug antiretroviral prophylaxis (tARVp (AZT+3TC+ NVP or nelfinavir. All regimens were stopped at delivery. CD4+ decline was defined as proportion of women who declined to CD4+ <350 cells/mm(3 or <200 cells/mm(3 at 24 months. Weibull regression was used for multivariable analysis. FINDINGS: A total of 1,393 women with enrollment CD4+ ≥250 cells/mm(3 initiated tARVp (172; 12% or sc-ARVp (532; 38% during pregnancy or received intrapartum sd-NVP (689; 50%. At enrollment, maternal median age was 27 years (interquartile range (IQR 23-30, median CD4+ was 469 cells/mm(3 (IQR: 363-613. At 24 months post-delivery, the cumulative probability of CD4+ decline to <200 cells/mm(3 was 12% (95% CI: 10-14. Among a subgroup of 903 women with CD4+ ≥400 cells at enrollment, the 24 month cumulative probability of decline to CD4+ <350 cells/mm(3 was 28%; (95% CI: 25-32. Lower antepartum CD4+ was associated with higher probability of CD4+ decline to <350 cells/mm(3: 46% (CD4+400-499 cells/mm(3 vs. 19% (CD4+ ≥500 cells/mm(3. After adjusting for age, enrollment CD4+ and WHO stage, women who received tARVp or sd-NVP were twice as likely to experience CD4+ decline to <350 cells/mm(3 within 24 months than women receiving sc-ARVp (adjusted hazard ratio: 2.2; 95% CI: 1.5-3.2, p<0.0001. CONCLUSION: Decline in CD4+ cell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery.

  10. Psychosocial factors affecting medication adherence among HIV-1 infected adults receiving combination antiretroviral therapy (cART) in Botswana.

    Science.gov (United States)

    Do, Natalie T; Phiri, Kelesitse; Bussmann, Hermann; Gaolathe, Tendani; Marlink, Richard G; Wester, C William

    2010-06-01

    As increasing numbers of persons are placed on potentially life-saving combination antiretroviral therapy (cART) in sub-Saharan Africa, it is imperative to identify the psychosocial and social factors that may influence antiretroviral (ARV) medication adherence. Using an 87 question survey, the following data were collected from patients on cART in Botswana: demographics, performance (Karnofsky) score, perceived stigma and level of HIV disclosure, attitudes and beliefs concerning HIV/AIDS, substance and/or drug use, depression, and pharmacy and healthcare provider-related factors. Overall adherence rates were determined by patient self-report, institutional adherence, and a culturally modified Morisky scale. Three hundred adult patients were recruited between April and May 2005. The overall cART adherence rate was 81.3% based on 4 day and 1 month patient recall and on clinic attendance for ARV medication refills during the previous 3 months. Adults receiving cART for 1-6 months were the least adherent (77%) followed by those receiving cART for greater than 12 months (79%). Alcohol use, depression, and nondisclosure of positive HIV status to their partner were predictive of poor adherence rates (p value HIV disclosure to "at-risk" partners and provide ongoing counseling and education to help patients recognize and overcome HIV-associated stigma, alcohol abuse, and depression.

  11. The impact of new antiretroviral treatments on college students' intention to use a condom with a new sexual partner.

    Science.gov (United States)

    Gagnon, M P; Godin, G

    2000-06-01

    The aim of this study was to evaluate possible changes in predisposing factors in sexual preventive behaviors that could result from the availability of an efficient new antiretroviral therapy. A total of 136 young adults were randomly assigned a vignette to read describing AIDS as a lethal or chronic disease. After reading the vignette, the participants completed a self-administered questionnaire assessing the psychosocial determinants of intention to use a condom with a new sexual partner. The variables were measured according to Ajzen's (1985, 1988, 1991) theory of planned behavior and Triandis's (1977) theory of interpersonal behavior. The experimental manipulation was more successful when the disease was described as lethal (66 of the 68 subjects) rather than chronic (30 of the 68 subjects). For the 96 participants who correctly identified the expected outcome of the disease presented in the vignette, a significant difference in intention was found between the two experimental situations (p intention to use condoms on the psychosocial variables yielded an adjusted R2 of .62. Perceived behavioral control, social norms, personal normative belief and anticipated affective reaction were the significant variables explaining this intention. The results suggest that intention to use condoms with a new sexual partner is likely to be modified by the expected outcome of the disease, that is, whether lethal or chronic. Thus, it is suggested that interventions aimed at young adults take into account the impacts the new antiretroviral treatments are likely to have on preventive behaviors.

  12. Personality Disorders

    Science.gov (United States)

    Personality disorders are a group of mental illnesses. They involve long-term patterns of thoughts and behaviors that ... serious problems with relationships and work. People with personality disorders have trouble dealing with everyday stresses and problems. ...

  13. Transcatheter arterial chemoembolization and radiation therapy for treatment-naive patients with locally advanced hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won [Dept. of Radiation Oncology, Yeungnam University Medical Center, Daegu (Korea, Republic of); Oh, Dong Ryul; Park, Hee Chul; Lim, Do Hoon; Shin, Sung Wook; Cho, Sung Ki; Gwak, Geum Youn; Choi, Moon Seok; Paik, Yong Han; Paik, Seung Woon [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) followed by radiotherapy (RT) in treatment-naive patients with locally advanced hepatocellular carcinoma (HCC). Eligibility criteria were as follows: newly diagnosed with HCC, the Barcelona Clinic Liver Cancer stage C, Child-Pugh class A or B, and no prior treatment for HCC. Patients with extrahepatic spread were excluded. A total of 59 patients were retrospectively enrolled. All patients were treated with TACE followed by RT. The time interval between TACE and RT was 2 weeks as per protocol. A median RT dose was 47.25 Gy10 as the biologically effective dose using the α/β = 10 (range, 39 to 65.25 Gy10). At 1 month, complete response was obtained in 3 patients (5%), partial response in 27 patients (46%), stable disease in 13 patients (22%), and progressive disease in 16 patients (27%). The actuarial one- and two-year OS rates were 60.1% and 47.2%, respectively. The median OS was 17 months (95% confidence interval, 5.6 to 28.4 months). The median time to progression was 4 months (range, 1 to 35 months). Grade 3 or greater liver enzyme elevation occurred in only two patients (3%) after RT. Grade 3 gastroduodenal toxicity developed in two patients (3%). The combination treatment of TACE followed by RT with two-week interval was safe and it showed favorable outcomes in treatment-naive patients with locally advanced HCC. A prospective randomized trial is needed to validate these results.

  14. The Galileo Bias: A Naive Conceptual Belief That Influences People's Perceptions and Performance in a Ball-Dropping Task

    Science.gov (United States)

    Oberle, Crystal D.; McBeath, Michael K.; Madigan, Sean C.; Sugar, Thomas G.

    2005-01-01

    This research introduces a new naive physics belief, the Galileo bias, whereby people ignore air resistance and falsely believe that all objects fall at the same rate. Survey results revealed that this bias is held by many and is surprisingly strongest for those with formal physics instruction. In 2 experiments, 98 participants dropped ball pairs…

  15. Predicting Ecstasy Use among Young People at Risk: A Prospective Study of Initially Ecstasy-Naive Subjects

    Science.gov (United States)

    Vervaeke, Hylke K.E.; Benschop, Annemieke; Van Den Brink, Wim; Korf, Dirk J.

    2008-01-01

    Our aim is to identify predictors of first-time ecstasy use in a prospective study among young people at risk. As part of the multidisciplinary Netherlands XTC Toxicity Study (NeXT), we monitored 188 subjects aged up to 18 years who were ecstasy-naive at baseline but seemed likely to start taking ecstasy in the near future. After an 11- to…

  16. Predicting ecstasy use among young people at risk: a prospective study of initially ecstasy-naive subjects

    NARCIS (Netherlands)

    H.K.E. Vervaeke; A. Benschop; W. van den Brink; D.J. Korf

    2008-01-01

    Our aim is to identify predictors of first-time ecstasy use in a prospective study among young people at risk. As part of the multidisciplinary Netherlands XTC Toxicity Study (NeXT), we monitored 188 subjects aged ≥ 18 who were ecstasy-naive at baseline but seemed likely to start taking ecstasy in t

  17. Ribavirin rather than PEG-interferon pharmacodynamics predict nonresponse to antiviral therapy in naive chronic hepatitis C patients.

    NARCIS (Netherlands)

    Vlerken, L.G. Van; Huisman, E.J.; Soest, H. van; Boland, G.J.; Drenth, J.P.H.; Siersema, P.D.; Burger, D.M.; Erpecum, K.J. van

    2012-01-01

    Twenty to fifty per cent of patients with chronic hepatitis C (CHC) experience nonresponse to current antiviral therapy, which may relate in part to ribavirin or PEG-interferon pharmacodynamics. We evaluated potential relevance of various factors for nonresponse. Two hundred forty-two naive CHC pati

  18. Nonspecific Effect of Stress on Brain Gray Matter Volume in Drug-naive Female Patients with First Depressive Episode

    Directory of Open Access Journals (Sweden)

    Chuan-Jun Zhuo

    2016-01-01

    Conclusions: Although the results of the present study suggest the absence of significant differences in brain gray matter volume between female drug-naive patients after the first episode of major depression with and without SLEs after FDR correction, the study provides useful information for exploring the definitive role of stress in the onset of depression.

  19. Altered Pattern of Naive and Memory B cells and B1 Cells in Patients with Chronic Granulomatous Disease

    NARCIS (Netherlands)

    Mohsenzadegan, Monireh; Fattahi, Fahimeh; Fattahi, Fatemeh; Mirshafiey, Abbas; Fazlollahi, Mohammad Reza; Beni, Fariba Naderi; Movahedi, Masoud; Pourpak, Zahra

    2014-01-01

    Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder characterized by a greatly increased susceptibility to severe fungal and bacterial infections caused by defects in NADPH oxidase of phagocytic cells. We aimed to investigate immunophenotype alterations of naive and memor

  20. A Discrete Choice Conjoint Experiment to Evaluate Parent Preferences for Treatment of Young, Medication Naive Children with ADHD

    Science.gov (United States)

    Waschbusch, Daniel A.; Cunningham, Charles E.; Pelham, William E., Jr.; Rimas, Heather L.; Greiner, Andrew R.; Gnagy, Elizabeth M.; Waxmonsky, James; Fabiano, Gregory A.; Robb, Jessica A.; Burrows-MacLean, Lisa; Scime, Mindy; Hoffman, Martin T.

    2011-01-01

    The current study examined treatment preferences of 183 parents of young (average age = 5.8 years, SD = 0.6), medication naive children with ADHD. Preferences were evaluated using a discrete choice experiment in which parents made choices between different combinations of treatment characteristics, outcomes, and costs. Latent class analysis…

  1. Autotaxin-mediated lipid signaling intersects with LIF and BMP signaling to promote the naive pluripotency transcription factor program

    Science.gov (United States)

    Kime, Cody; Sakaki-Yumoto, Masayo; Goodrich, Leeanne; Hayashi, Yohei; Sami, Salma; Derynck, Rik; Asahi, Michio; Panning, Barbara; Yamanaka, Shinya; Tomoda, Kiichiro

    2016-01-01

    Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion. BMP4, which also stimulates conversion to naive pluripotency, bypassed the need for exogenous LPA by increasing the activity of the extracellular LPA-producing enzyme autotaxin (ATX). We found that LIF and LPA-LPAR1 signaling affect the abundance of signal transducer and activator of transcription 3 (STAT3), which induces a previously unappreciated Kruppel-like factor (KLF)2-KLF4-PR domain 14 (PRDM14) transcription factor circuit key to establish naive pluripotency. AA also affects this transcription factor circuit by controlling PRDM14 expression. Thus, our study reveals that ATX-mediated autocrine lipid signaling promotes naive pluripotency by intersecting with LIF and BMP4 signaling. PMID:27738243

  2. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study

    DEFF Research Database (Denmark)

    Worm, Signe Westring; Sabin, Caroline; Weber, Rainer

    2010-01-01

    BACKGROUND. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS. Poisson regression models were adjusted for cardiovascular risk......% CI, 1.01-1.17], respectively) after adjustment for lipids but were not altered further after adjustment for other metabolic parameters. CONCLUSIONS. Of the drugs considered, only indinavir, lopinavir-ritonavir, didanosine, and abacavir were associated with a significantly increased risk of MI...... factors, cohort, calendar year, and use of other antiretroviral drugs and assessed the association between MI risk and cumulative (per year) or recent (current or in the past 6 months) use of antiretroviral drugs, with >30,000 person-years of exposure. RESULTS. Over 178,835 person-years, 580 patients...

  3. Factor structure of the Beck Depression Inventory-II among South Africans receiving antiretroviral therapy.

    Science.gov (United States)

    Kagee, Ashraf; Nel, Adriaan; Saal, Wylene

    2014-02-01

    Considerable evidence suggests that mood disturbance is common among patients living with HIV and may be an important barrier to anti-retroviral therapy (ART) adherence. Thus the assessment of depressed mood is an important and necessary aspect of the experience of persons living with HIV as it may impact the health status of individuals directly and indirectly. We sought to determine the factor structure of the Beck Depression Inventory (BDI) among a sample of 185 South Africans living with HIV and receiving ART. The mean BDI score was 16.5 (SD 12.15) with a range from 0-50 (out of a possible 63), indicating on average moderate levels of depression. Cronbach's alpha for the total scale was 0.90. Although the four factors had eigenvalues that were technically above 1.0, only three factors could logically be extracted, the combination of which accounted for 47.29% of the variance. These three factors were Cognitive, Affective and Somatic. The results indicate that the BDI-II is a reliable measure of symptoms of depression among persons living with HIV. The factor structure among South Africans receiving ART is similar to that of other samples, although surprisingly, the item assessing appetite disturbance did not load on any factor. The results of the study suggest that the BDI-II is a useful measure among South Africans living with HIV. In the context of the need to rapidly identify depressed mood among persons receiving ART in public health clinics, the BDI may be a useful instrument. We end the paper with certain cautions associated with routine screening.

  4. Antiretroviral Treatment-Associated Tuberculosis in a Prospective Cohort of HIV-Infected Patients Starting ART

    Directory of Open Access Journals (Sweden)

    William Worodria

    2011-01-01

    Full Text Available Commencement of antiretroviral treatment (ART in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4% patients were diagnosed with TB during followup. Eight (3.8% patients had ART-associated TB (incidence rate of 4.3 per 100 person years; of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years. A body mass index of less than 18.5 kg/m2 BMI (HR 5.85 95% CI 1.24–27.46, P=.025 and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36–38.33, P=.020 were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray, the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence.

  5. Antiretroviral treatment-associated tuberculosis in a prospective cohort of HIV-infected patients starting ART.

    Science.gov (United States)

    Worodria, William; Massinga-Loembe, Marguerite; Mayanja-Kizza, Harriet; Namaganda, Jane; Kambugu, Andrew; Manabe, Yukari C; Kestens, Luc; Colebunders, Robert

    2011-01-01

    Commencement of antiretroviral treatment (ART) in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB) disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI) consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4%) patients were diagnosed with TB during followup. Eight (3.8%) patients had ART-associated TB (incidence rate of 4.3 per 100 person years); of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years). A body mass index of less than 18.5 kg/m(2) BMI (HR 5.85 95% CI 1.24-27.46, P = .025) and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36-38.33, P = .020) were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray), the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence.

  6. Low Rate of Transmitted Drug Resistance May Indicate Low Access to Antiretroviral Treatment in Maranhão State, Northeast Brazil

    Science.gov (United States)

    Moura, Maria Edileuza Soares; da Guarda Reis, Mônica Nogueira; Lima, Yanna Andressa Ramos; Eulálio, Kelsen Dantas; Cardoso, Ludimila Paula Vaz

    2015-01-01

    Abstract The Brazilian AIDS epidemic is characterized by significant geographic contrasts: a reduction in incidence and mortality in the epicenter (southeast) and an increase in the northeast. HIV-1-transmitted drug resistance (TDR) and genetic diversity were investigated among 106 antiretroviral (ARV)-naive patients from Maranhão State, northeast. The HIV-1 protease (PR) and reverse transcriptase (RT) regions were sequenced; subtypes were assigned by REGA/phylogenetic analysis. TDR to the nucleoside/nonnucleoside reverse transcriptase inhibitor (NRTI/NNRTI) and protease inhibitor (PI) was identified by the Calibrated Population Resistance tool (Stanford). The median age was 31 years (range 18–72), with 54.7% women, 78.3% heterosexual transmission, and 17.9% men who have sex with men (MSM). Around 30% had <350 CD4+ T cells/μl and 47.2% had plasma viral loads ≤10,000 copies/ml. The TDR rate was 3.8% (4/106; CI 95%, 1.2–8.9%) (three males, two of them MSM). Only single class mutations to NRTI (M184V; T215S) or NNRTI (K103S/N) were detected. Subtype B represented 81.1% (86/106), F1 1.9% (2/106), and C 2.8% (3/106); 14.2% were mosaics: 13 BF1 and 2 BC. Surveillance of TDR and HIV-1 genetic diversity is important to improve control strategies regionally. PMID:25411830

  7. Strategies for Living with the Challenges of HIV and Antiretroviral Use in Zambia

    Science.gov (United States)

    Jones, Deborah; Zulu, Isaac; Mumbi, Miriam; Chitalu, Ndashi; Vamos, Szonja; Gomez, Jacqueline; Weiss, Stephen M.

    2009-01-01

    This study sought to identify strategies for living with the challenges of HIV and antiretroviral (ARV) use among new medication users in urban Zambia. Participants (n = 160) were recruited from urban Lusaka, Zambia. Qualitative Data was drawn from monthly ARV treatment education intervention groups addressing HIV and antiretroviral use. Themes…

  8. Adherence to national guidelines for initiation of antiretroviral regimens in HIV patients: a Danish nationwide study

    DEFF Research Database (Denmark)

    Petersen, Tonny; Andersen, Stig E; Gerstoft, Jan;

    2011-01-01

    To determine the adherence to the national guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients.......To determine the adherence to the national guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients....

  9. Possible drug-metabolism interactions of medicinal herbs with antiretroviral agents.

    NARCIS (Netherlands)

    Beukel, C. van den; Koopmans, P.P.; Ven, A.J.A.M. van der; Smet, P.A.G.M. de; Burger, D.M.

    2006-01-01

    Herbal medicines are widely used by HIV patients. Several herbal medicines have been shown to interact with antiretroviral drugs, which might lead to drug failure. We have aimed to provide an overview of the modulating effects of Western and African herbal medicines on antiretroviral drug-metabolizi

  10. The prevalence of metabolic syndrome in Danish patients with HIV infection: the effect of antiretroviral therapy

    DEFF Research Database (Denmark)

    Hansen, Birgitte Rønde; Petersen, J; Haugaard, S B;

    2009-01-01

    OBJECTIVES: The prevalence of metabolic syndrome (MS) in HIV-infected patients on highly active antiretroviral therapy (HAART) is a subject of debate. We investigated the prevalence of MS in a cohort of Danish HIV-infected patients and estimated the effect of the various classes of antiretroviral...

  11. HIV-1 subtypes and response to combination antiretroviral therapy in Europe

    DEFF Research Database (Denmark)

    Bannister, WP; Ruiz, L; Loveday, C;

    2006-01-01

    BACKGROUND: Combination antiretroviral therapy (cART) may vary in ability to suppress viral load and increase CD4+ T-cell count in people infected with different HIV-1 subtypes, possibly due to differences in resistance development. Antiretroviral drugs have predominantly been developed in Western...

  12. Persistent Inflammation and Endothelial Activation in HIV-1 Infected Patients after 12 Years of Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L;

    2013-01-01

    The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART).......The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART)....

  13. Is there a role for generic antiretroviral drugs in the United States?

    Science.gov (United States)

    Wormser, Gary P; Lappas, Thomas

    2014-08-01

    The high cost of antiretroviral drugs has limited access to treatment for some HIV-infected patients in the United States and strained public resources. With the introduction of much cheaper generic versions of some of these agents, and with more to come in the next few years, the need increases to define the role of generic antiretroviral drugs in patient management.

  14. Evaluation of HIV/AIDS patients' knowledge on antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Regina Flávia de Castro Almeida

    2009-06-01

    Full Text Available Lack of information on antiretroviral drugs or the misunderstanding of available information can facilitate incorrect use of such drugs. This can result in non-adherence to the prescribed regimen, leading to a great possibility of a therapeutic failure. The aim of this study was to know which information HIV/AIDS patients, who receive their medicines at the pharmacy of a reference hospital in the northeast Brazil, have on the drugs they use, the source of this information and whether there is a need for additional information. A total of 195 HIV/AIDS patients, who were using either zidovudina + lamivudina 300+150mg (AZT+3TC, efavirenz 600mg (EFZ or lopinavir/ritonavir 133.33/33mg (LPV/r, were interviewed. The mean age was 41 years (SD = 9.55 and 70.8% were males. Of the total, 55.4% didn't know the effect of the drug in the organism; 35.9% were unaware of the necessity of taking antiretroviral drugs for the rest of their lives; only 14.4% knew how to proceed when a dosage was missed; 22.1% said they could die and the same number of individuals believed in aggravation of the disease in case of treatment interruption. The majority, 68.2%, considered it very necessary to receive drug information. The results show that there is an apparent lack of general information among users of antiretroviral drugs, and at the same time a need for it. It is necessary that all professionals involved in the health care of the patients agree that an efficient supply of information on prescribed drugs is an ethical component of the treatment that favors and fosters its adherence.

  15. 1,25-dihydroxyvitamin D{sub 3} impairs NF-{kappa}B activation in human naive B cells

    Energy Technology Data Exchange (ETDEWEB)

    Geldmeyer-Hilt, Kerstin, E-mail: kerstin.hilt@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Heine, Guido, E-mail: guido.heine@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Hartmann, Bjoern, E-mail: bjoern.hartmann@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Baumgrass, Ria, E-mail: baumgrass@drfz.de [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Radbruch, Andreas, E-mail: radbruch@drfz.de [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Worm, Margitta, E-mail: margitta.worm@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany)

    2011-04-22

    Highlights: {yields} In naive B cells, VDR activation by calcitriol results in reduced NF-{kappa}B p105 and p50 protein expression. {yields} Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-{kappa}B p65. {yields} Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. {yields} Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1{alpha},25-dihydroxyvitamin D{sub 3} (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-{kappa}B p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-{kappa}B mediated activation of human naive B cells. Naive B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naive B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-{kappa}B activation by interference with NF-{kappa}B p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.

  16. Overview of antiretroviral treatment in China: advancement and challenges

    Institute of Scientific and Technical Information of China (English)

    LUO Ling; LI Tai-sheng

    2011-01-01

    As the severity of the HIV epidemic in China grew, National Free Antiretroviral Treatment (ART) Program was announced since 2003. Even though there still were many difficulties, China had obtained great achievements in fighting against HIV.Over 52 000 adult patients had received first-line HAART thus far and the mortality of AIDS in China decreased significantly. This paper presents an overview of the HIV/AIDS epidemic in China; the status of national free ART program,the difficulties suffered and the achievements made since the initiation of program and the challenges ahead for continued progress for China. This paper also provides suggestions to overcome these challenges.

  17. Outcomes of Universal Access to Antiretroviral Therapy (ART) in Georgia

    OpenAIRE

    Tengiz Tsertsvadze; Nikoloz Chkhartishvili; Lali Sharvadze; Natia Dvali; Otar Chokoshvili; Pati Gabunia; Akaki Abutidze; Kenrad Nelson; Jack DeHovitz; Carlos del Rio

    2011-01-01

    Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/mm3. During followup, 152 (...

  18. Combination antiretroviral drugs in PLGA nanoparticle for HIV-1

    Directory of Open Access Journals (Sweden)

    Sharma Akhilesh

    2009-12-01

    Full Text Available Abstract Background Combination antiretroviral (AR therapy continues to be the mainstay for HIV treatment. However, antiretroviral drug nonadherence can lead to the development of resistance and treatment failure. We have designed nanoparticles (NP that contain three AR drugs and characterized the size, shape, and surface charge. Additionally, we investigated the in vitro release of the AR drugs from the NP using peripheral blood mononuclear cells (PBMCs. Methods Poly-(lactic-co-glycolic acid (PLGA nanoparticles (NPs containing ritonavir (RTV, lopinavir (LPV, and efavirenz (EFV were fabricated using multiple emulsion-solvent evaporation procedure. The nanoparticles were characterized by electron microscopy and zeta potential for size, shape, and charge. The intracellular concentration of AR drugs was determined over 28 days from NPs incubated with PBMCs. Macrophages were imaged by fluorescent microscopy and flow cytometry after incubation with fluorescent NPs. Finally, macrophage cytotoxicity was determined by MTT assay. Results Nanoparticle size averaged 262 ± 83.9 nm and zeta potential -11.4 ± 2.4. AR loading averaged 4% (w/v. Antiretroviral drug levels were determined in PBMCs after 100 μg of NP in 75 μL PBS was added to media. Intracellular peak AR levels from NPs (day 4 were RTV 2.5 ± 1.1; LPV 4.1 ± 2.0; and EFV 10.6 ± 2.7 μg and continued until day 28 (all AR ≥ 0.9 μg. Free drugs (25 μg of each drug in 25 μL ethanol added to PBMCs served as control were eliminated by 2 days. Fluorescence microscopy and flow cytometry demonstrated phagocytosis of NP into monocytes-derived macrophages (MDMs. Cellular MTT assay performed on MDMs demonstrated that NPs are not significantly cytotoxic. Conclusion These results demonstrated AR NPs could be fabricated containing three antiretroviral drugs (RTV, LPV, EFV. Sustained release of AR from PLGA NP show high drug levels in PBMCs until day 28 without cytotoxicity.

  19. Personality and personal network type

    NARCIS (Netherlands)

    Doeven-Eggens, Lilian; De Fruyt, Filip; Hendriks, A. A. Jolijn; Bosker, Roel J.; Van der Werf, Margaretha P. C.

    2008-01-01

    The association between personality and personal relationships is mostly studied within dyadic relationships. We examined these variables within the context of personal network types. We used Latent Class Analysis to identify groups Of Students with similar role relationships with three focal figure

  20. Change in serum 25-hydroxyvitamin D with antiretroviral treatment initiation and nutritional intervention in HIV-positive adults

    DEFF Research Database (Denmark)

    Yilma, Daniel; Kæstel, Pernille; Olsen, Mette F;

    2016-01-01

    Low vitamin D level in HIV-positive persons has been associated with disease progression. We compared the levels of serum 25-hydroxyvitamin D (25(OH)D) in HIV-positive and HIV-negative persons, and investigated the role of nutritional supplementation and antiretroviral treatment (ART) on serum 25...... daily allowance of vitamin D (10 μg/200 g). The level of serum 25(OH)D before nutritional intervention and ART initiation was compared with serum 25(OH)D of HIV-negative individuals. A total of 348 HIV-positive and 100 HIV-negative persons were recruited. The median baseline serum 25(OH)D level......-supplemented group had a 10·8 (95 % CI 7·8, 13·9) nmol/l decrease in serum 25(OH)D level after 3 months of ART. Nutritional supplementation that contained vitamin D prevented a reduction in serum 25(OH)D levels in HIV-positive persons initiating ART. Vitamin D replenishment may be needed to prevent reduction...

  1. A Multilevel Conceptual Framework to Understand the Role of Food Insecurity on Antiretroviral Therapy Adherence in Low-Resource Settings: From Theory to Practice.

    Science.gov (United States)

    Masa, Rainier; Chowa, Gina

    2017-04-03

    The objective of this study was to describe a multilevel conceptual framework to understand the role of food insecurity on antiretroviral therapy adherence. The authors illustrated an example of how they used the multilevel framework to develop an intervention for poor people living with HIV in a rural and low-resource community. The framework incorporates intrapersonal, interpersonal, and structural-level theories of understanding and changing health behaviors. The framework recognizes the role of personal, social, and environmental factors on cognition and behavior, with particular attention to ways in which treatment adherence is enabled or prevented by structural conditions, such as food insecurity.

  2. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study

    DEFF Research Database (Denmark)

    Babiker, Abdel G; Emery, Sean; Fätkenheuer, Gerd

    2013-01-01

    Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an incr...... is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals....... with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication...

  3. Potential impact on HIV incidence of higher HIV testing rates and earlier antiretroviral therapy initiation in MSM

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Cambiano, Valentina; Miners, Alec

    2015-01-01

    BACKGROUND: Increased rates of testing, with early antiretroviral therapy (ART) initiation, represent a key potential HIV-prevention approach. Currently, in MSM in the United Kingdom, it is estimated that 36% are diagnosed by 1 year from infection, and the ART initiation threshold is at CD4 cell...... on HIV in MSM in the United Kingdom. Outcomes were projected according to future alternative HIV testing and ART initiation scenarios to 2030, considering also potential changes in levels of condomless sex. RESULTS: For ART use to result in an incidence of close to 1/1000 person-years requires...... the proportion of all HIV-positive MSM with viral suppression to increase from below 60% currently to 90%, assuming no rise in levels of condomless sex. Substantial increases in HIV testing, such that over 90% of men are diagnosed within a year of infection, would increase the proportion of HIV-positive men...

  4. Personality traits and personality disorders.

    Science.gov (United States)

    Deary, I J; Peter, A; Austin, E; Gibson, G

    1998-11-01

    The structure of personality disorder traits was examined in a sample of 400 undergraduates who completed the personality disorder questionnaire from the Structured Clinical Interview for DSM-III-R (SCID-II). The relations between personality disorder and normal personality traits indexed by the Eysenck Personality Questionnaire-Revised (EPQ-R) were examined. The three-cluster model of personality traits--as described in the DSM scheme--found equivocal support. Exploratory principal components analysis and confirmatory factor analysis found four broad factors of personality disorder that overlapped with normal personality traits: an asthenic factor related to neuroticism; an antisocial factor associated with psychoticism; an asocial factor linked to introversion-extraversion; and an anankastic (obsessive-compulsive) factor. There is growing agreement about the number and type of broad personality disorder dimensions; similar dimensions may be found in clinical and non-clinical samples, suggesting that those people with personality disorders differ quantitatively rather than qualitatively from others; and there is substantial overlap between normal and abnormal personality dimensions.

  5. Antiretroviral Treatment Adherence: Knowledge and Experiences among Adolescents and Young Adults in Soweto, South Africa

    Directory of Open Access Journals (Sweden)

    Stefanie Hornschuh

    2017-01-01

    Full Text Available Human immunodeficiency virus (HIV management of adolescents and young adults (AYAs is particularly pertinent to sub-Saharan Africa, where the pediatric HIV burden is marked. Antiretroviral treatment (ART adherence is a major challenge for AYAs. This qualitative study explored knowledge and experiences of adherence amongst AYAs attending treatment at the Perinatal HIV Research Unit (PHRU, Soweto, South Africa. Four focus group discussions (FGDs and eight in-depth interviews (IDIs were conducted with HIV-infected 15–25-year-old ART recipients. Transcripts were coded thematically. Participants (n=26 were aged median 18.5 years, 59.1% female and 69.2% virally suppressed <400 cp/ml. Three main themes emerged during FGDs and IDIs: (i correct knowledge about how to be adherent, benefits, and nonadherence consequences, (ii social, personal, and medication-related barriers to adherence, and (iii reminder, concealment, and motivational strategies to optimize adherence. Interventions to improve AYA adherence could focus on practical strategies, including status disclosure and medication concealment.

  6. Patient and regimen characteristics associated with self-reported nonadherence to antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Patrick S Sullivan

    Full Text Available BACKGROUND: Nonadherence to antiretroviral therapy (ARVT is an important behavioral determinant of the success of ARVT. Nonadherence may lead to virological failure, and increases the risk of development of drug resistance. Understanding the prevalence of nonadherence and associated factors is important to inform secondary HIV prevention efforts. METHODOLOGY/PRINCIPAL FINDINGS: We used data from a cross-sectional interview study of persons with HIV conducted in 18 U.S. states from 2000-2004. We calculated the proportion of nonadherent respondents (took or=4 medications; living in a shelter or on the street; and feeling "blue" >or=14 of the past 30 days. We found weaker associations with having both male-male sex and injection drug use risks for HIV acquisition; being prescribed ARVT for >or=21 months; and being prescribed a protease inhibitor (PI-based regimen not boosted with ritonavir. The median proportion of doses missed was 50%. The most common reasons for missing doses were forgetting and side effects. CONCLUSIONS/SIGNIFICANCE: Self-reported recent nonadherence was high in our study. Our data support increased emphasis on adherence in clinical settings, and additional research on how providers and patients can overcome barriers to adherence.

  7. The impact of antiretroviral therapy in resource-limited settings and current HIV therapeutics.

    Science.gov (United States)

    Kumarasamy, N

    2016-04-01

    Four million people of the global total of 35 million with HIV infection are from South-East Asia. ART is currently utilized by 15 million people and has led to a dramatic decline in the mortality rate, including those in low- and middle-income countries. A reduction in sexually transmitted HIV and in comorbidities including tuberculosis has also followed. Current recommendations for the initiation of antiretroviral therapy in people who are HIV+ are essentially to initiate ART irrespective of CD4 cell count and clinical stage. The frequency of HIV testing should be culturally specific and based on the HIV incidence in different key populations but phasing in viral load technology in LMIC is an urgent priority and this needs resources and capacity. With the availability of simplified potent ART regimens, persons with HIV now live longer. The recent WHO treatment guidelines recommending routine HIV testing and earlier initiation of treatment should be the stepping stone for ending the AIDS epidemic and to meet the UNAIDS mission of 90*90*90.

  8. Risk factors for intestinal parasitosis among antiretroviral-treated HIV/AIDS patients in Ethiopia.

    Science.gov (United States)

    Mahmud, Mahmud Abdulkader; Bezabih, Afework Mulugeta; Gebru, Rezene Berhe

    2014-10-01

    Summary A cross-sectional survey was conducted to determine the risk factors associated with intestinal parasitosis in HIV/AIDS patients receiving antiretroviral therapy (ART). Socio-demographic information was collected and faecal samples were analysed from 384 randomly selected patients on ART. Data on CD4+ T-cell counts and World Health Organization clinical staging were obtained from the medical records at the hospital. The overall prevalence of intestinal parasitosis was 56% (95% confidence interval [CI]: 51% to 61%). No opportunistic intestinal parasites or Schistosoma haematobium eggs were detected. Unavailability of latrine and lack of hand washing with soap were associated with Entamoeba histolytica/dispar (adjusted odds ratio [AOR], 2.75; 95% CI: 1.77 to 4.27 and AOR, 2.67; 95% CI: 1.60 to 4.44, respectively) and Giardia lamblia (AOR, 2.08; 95% CI: 1.08 to 3.99 and AOR, 2.46; 95% CI: 1.06 to 5.75, respectively) infections. Intestinal parasitosis was significantly associated with low CD4 cell count (p = 0.002). In contrast, intestinal parasitic infections were not associated (p > 0.05) with the World Health Organization disease staging. In summary, poor personal hygiene and sanitation practice contributed to the high prevalence of intestinal parasitosis. Routine diagnosis for intestinal parasitic infections should be performed in patients attending ART clinics in this setting.

  9. HIV Transmission Risk Persists During the First 6 Months of Antiretroviral Therapy

    Science.gov (United States)

    Mujugira, Andrew; Celum, Connie; Coombs, Robert W.; Campbell, James D.; Ndase, Patrick; Ronald, Allan; Were, Edwin; Bukusi, Elizabeth A.; Mugo, Nelly; Kiarie, James; Baeten, Jared M.

    2016-01-01

    Objective Combination antiretroviral therapy (ART) decreases the risk of sexual HIV transmission by suppressing blood and genital HIV RNA concentrations. We sought to determine HIV transmission risk prior to achieving complete viral suppression. Design Prospective cohort study. Methods Using data from the Partners PrEP Study, a prospective study of 4747 heterosexual HIV-serodiscordant couples in Kenya and Uganda, we examined multiple markers of HIV transmission risk during the first months after ART initiation: time to viral suppression in blood, persistence of HIV RNA in genital specimens, sexual risk behavior, pregnancy incidence, and HIV transmission using survival analysis and GEE logistic regression. Results The cumulative probabilities of achieving blood viral suppression (6 months of ART (0 infections; 167 person-years). Conclusions Residual HIV transmission risk persists during the first 6-months of ART, with incomplete viral suppression in blood and genital compartments. For HIV-serodiscordant couples in which the infected partner starts ART, other prevention options are needed, such as pre-exposure prophylaxis, until viral suppression is achieved. PMID:27070123

  10. Personality Development

    Directory of Open Access Journals (Sweden)

    Osman Ozdemir

    2012-12-01

    Full Text Available Personality is the integration of characteristics acquired or brought by birth which separate the individual from others. Personality involves aspects of the individual's mental, emotional, social, and physical features in continuum. Several theories were suggested to explain developmental processes of personality. Each theory concentrates on one feature of human development as the focal point, then integrates with other areas of development in general. Most theories assume that childhood, especially up to 5-6 years, has essential influence on development of personality. The interaction between genetic and environmental factors reveals a unique personality along growth and developmental process. It could be said that individual who does not have any conflict between his/her basic needs and society's, has well-developed and psychologically healthy personality.

  11. Sclerosing cholangitis by cytomegalovirus in highly active antiretroviral therapy era

    Directory of Open Access Journals (Sweden)

    Carmen Hidalgo-Tenorio

    2013-10-01

    Full Text Available Sclerosing colangitis (SC due to cytomegalovirus (CMV is very rare. It has been described mainly in immunocompromised patients. Currently, in HIV infected patients it is exceptional. The most of cases belong to pre-highly active antiretroviral therapy (pre-HAART and those cases were in stage AIDS with less than 100 CD4/μl. The most frequently involved pathogen in pre-HAART period was Cryptosporidium parvum (30-57% and CMV (10-30%; in late HAART period this information are unaware. CMV has been implicated as a possible etiological agent in primary SC partly because of the ability to cause liver damage and its relationship with smooth muscle antibodies. The most effective treatment for SC was the combination of antiretroviral therapy and endoscopic retrograde cholangiopancreatography with sphincterotomy and stent placement. Following, we present the first case of late HAART period which describes a SC extrahepatic without papillary stenosis with CMV as the only cause and clinical presentation of HIV infection in a woman with 177 CD4/μl.

  12. Drug-drug interactions: antiretroviral drugs and recreational drugs.

    Science.gov (United States)

    Staltari, Orietta; Leporini, Christian; Caroleo, Benedetto; Russo, Emilio; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

    2014-01-01

    With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrates of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reversetranscriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but show several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs.

  13. Intellectual property rights, market competition and access to affordable antiretrovirals.

    Science.gov (United States)

    Pascual, Fernando

    2014-01-01

    The number of patients receiving antiretroviral therapy (ART) has increased from around half a million in 2003 to almost 10 million in only 10 years, and will continue to increase in the coming years. Over 16 million more are eligible to start ART according to the last World Health Organization (WHO) guidelines. The demand is also switching from the less expensive antiretrovirals (ARVs) that allowed such scale-up to newer more expensive ones with fewer side effects or those that can be used by people who have developed resistance to first-line treatment. However, patents on these new drugs can delay robust generic competition and, consequently, price reduction made possible by economies of scale. Various ways to address this issue have been envisaged or implemented, including the use of the flexibilities available under the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), systematic widespread voluntary licensing, of which the Medicines Patent Pool (MPP) is an example, and the application of different prices in different countries, called tiered pricing. This paper helps explain the impact of patents on market competition for ARVs and analyses various approaches available today to minimize this impact.

  14. [Positioning of lopinavir/ritonavir in antiretroviral treatment schemes].

    Science.gov (United States)

    Camacho, Ángela; Rivero, Antonio

    2014-11-01

    Lopinavir/ritonavir (LPV/r) was approved for use in the treatment of human immunodeficiency virus (HIV) infection in 2001 and is the protease inhibitor that has been most widely studied in clinical trials. Despite the time interval since its approval, all the evidence accumulated in the last 14 years indicates that LPV/r continues to occupy an important position among antiretroviral drugs. Firstly, LPV/r plus 2 nucleoside/nucleotide analogs is still considered a good option for initial antiretroviral therapy (ART). Secondly, numerous studies have evaluated the efficacy and safety of new initial ART strategies based on LPV/r in dual therapy. The results obtained suggest that LPV/r plus lamivudine (3TC) or raltegravir can be as effective in initial ART as standard triple therapy and justify their consideration as alternative regimens in this scenario. Thirdly, LPV/r is a pioneer drug, as well as being the agent with the largest amount of evidence from clinical trials on simplification to monotherapy (LPV/r) or dual therapy (LPV/r + 3TC). Lastly, LPV/r is highly useful is special situations. It has a low risk of liver toxicity in patients with chronic liver disease, its use is preferred in the treatment of patients with HIV-2, and it is safe and effective in preventing vertical HIV transmission.

  15. Negotiation Strategies for Antiretroviral Drug Purchasers in the United States.

    Science.gov (United States)

    Linnemayr, Sebastian; Ryan, Gery W; Karir, Veena; Liu, Jenny; Palar, Kartika

    2012-01-01

    Antiretroviral treatment has transformed HIV from a death sentence to a chronic condition, allowing people with HIV to live longer and healthier lives. However, they face significant barriers to accessing and affording life-saving-but expensive-antiretroviral (ARV) medications. These barriers are particularly severe for low-income patients, and they disproportionately affect racial and ethnic minorities. High ARV prices create pressure for government insurers to contain costs either by rationing care or by restricting eligibility for public programs. Limited funding, coupled with a growing demand for HIV care and treatment, is likely to make programmatic decisions about who is covered become more difficult over time. Therefore, it is important to identify options for reducing the cost of providing ARVs to allow more people to receive treatment. This study examines a variety of options for negotiating lower ARV procurement costs in U.S. markets. A case-study approach is used to assess options that different stakeholders could use in negotiating ARV price discounts with drug manufacturers given the regulatory and market constraints that exist in the United States.

  16. HIV-Antiretroviral Therapy Induced Liver, Gastrointestinal, and Pancreatic Injury

    Directory of Open Access Journals (Sweden)

    Manuela G. Neuman

    2012-01-01

    Full Text Available The present paper describes possible connections between antiretroviral therapies (ARTs used to treat human immunodeficiency virus (HIV infection and adverse drug reactions (ADRs encountered predominantly in the liver, including hypersensitivity syndrome reactions, as well as throughout the gastrointestinal system, including the pancreas. Highly active antiretroviral therapy (HAART has a positive influence on the quality of life and longevity in HIV patients, substantially reducing morbidity and mortality in this population. However, HAART produces a spectrum of ADRs. Alcohol consumption can interact with HAART as well as other pharmaceutical agents used for the prevention of opportunistic infections such as pneumonia and tuberculosis. Other coinfections that occur in HIV, such as hepatitis viruses B or C, cytomegalovirus, or herpes simplex virus, further complicate the etiology of HAART-induced ADRs. The aspect of liver pathology including liver structure and function has received little attention and deserves further evaluation. The materials used provide a data-supported approach. They are based on systematic review and analysis of recently published world literature (MedLine search and the experience of the authors in the specified topic. We conclude that therapeutic and drug monitoring of ART, using laboratory identification of phenotypic susceptibilities, drug interactions with other medications, drug interactions with herbal medicines, and alcohol intake might enable a safer use of this medication.

  17. Using an Integrated Naive Bayes Calssifier for Crawling Relevent Data on the Web

    Science.gov (United States)

    Mihsra, A.

    2015-12-01

    In our experiments (at JPL, NASA) for DARPA Memex project, we wanted to crawl a large amount of data for various domains. A big challenge was data relevancy in the crawled data. More than 50% of the data was irrelevant to the domain at hand. One immediate solution was to use good seeds (seeds are the initial urls from where the program starts to crawl) and make sure that the crawl remains into the original host urls. This although a very efficient technique, fails under two conditions. One when you aim to reach deeper into the web; into new hosts (not in the seed list) and two when the website hosts myriad content types eg. a News website.The relevancy calculation used to be a post processing step i.e. once we had finished crawling, we trained a NaiveBayes Classifier and used it to find a rough relevancy of the web pages that we had. Integrating the relevancy into the crawling rather than after it was very important because crawling takes resources and time. To save both we needed to get an idea of relevancy of the whole crawl during run time and be able to steer its course accordingly. We use Apache Nutch as the crawler, which uses a plugin system to incorporate any new implementations and hence we built a plugin for Nutch.The Naive Bayes Parse Plugin works in the following way. It parses every page and decides, using a trained model (which is built in situ only once using the positive and negative examples given by the user in a very simple format), if it is relevant; If true, then it allows all the outlinks from that page to go to the next round of crawling; If not, then it gives the urls a second chance to prove themselves by checking some commonly expected words in the url relevant to that domain. This two tier system is very intuitive and efficient in focusing the crawl. In our initial test experiments over 100 seed urls, the results were astonishingly good with a recall of 98%.The same technique can be applied to geo-informatics. This will help scientists

  18. Agreement between physicians and non-physician clinicians in starting antiretroviral therapy in rural Uganda

    Directory of Open Access Journals (Sweden)

    Vasan Ashwin

    2009-08-01

    Full Text Available Abstract Background The scarcity of physicians in sub-Saharan Africa – particularly in rural clinics staffed only by non-physician health workers – is constraining access to HIV treatment, as only they are legally allowed to start antiretroviral therapy in the HIV-positive patient. Here we present a pilot study from Uganda assessing agreement between non-physician clinicians (nurses and clinical officers and physicians in their decisions as to whether to start therapy. Methods We conducted the study at 12 government antiretroviral therapy sites in three regions of Uganda, all of which had staff trained in delivery of antiretroviral therapy using the WHO Integrated Management of Adult and Adolescent Illness guidelines for chronic HIV care. We collected seven key variables to measure patient assessment and the decision as to whether to start antiretroviral therapy, the primary variable of interest being the Final Antiretroviral Therapy Recommendation. Patients saw either a clinical officer or nurse first, and then were screened identically by a blinded physician during the same clinic visit. We measured inter-rater agreement between the decisions of the non-physician health workers and physicians in the antiretroviral therapy assessment variables using simple and weighted Kappa analysis. Results Two hundred fifty-four patients were seen by a nurse and physician, while 267 were seen by a clinical officer and physician. The majority (> 50% in each arm of the study were in World Health Organization Clinical Stages I and II and therefore not currently eligible for antiretroviral therapy according to national antiretroviral therapy guidelines. Nurses and clinical officers both showed moderate to almost perfect agreement with physicians in their Final Antiretroviral Therapy Recommendation (unweighted κ = 0.59 and κ = 0.91, respectively. Agreement was also substantial for nurses versus physicians for assigning World Health Organization Clinical

  19. Nevirapine related hepatotoxicity: the prevalence and risk factors in a cohort of ART na(i)ve Han Chinese with AIDS%奈韦拉平相关肝毒性的发病率及危险因素

    Institute of Scientific and Technical Information of China (English)

    高世成; 桂希恩; 邓莉平; 张永喜; 严亚军; 荣玉萍; 梁科; 杨蓉蓉

    2010-01-01

    ART had at least one episode of ALT elevation during a median 21 months (interquartile ranges, IQR 6, 37) follow-up time,acounts for 28.5 cases per 100 person-years. Baseline ALT elevation (OR = 14.368, P = 0.017)and HCV coinfection (OR = 3.009, P = 0.000) were risk factors for cART related hepatotoxicity, while greatly increased CD4+T(CD4) cell count was protective against hepatotoxicity development (OR = 0.996, P = 0.000). Patients co-infected with HCV received NVP-based cART had the higher probability of hepatotoxicity than those without HCV co-infection (Log rank: x2 = 16.764, P = 0.000). 23 out of the 133 subjects (17.3%) with NVP related hepatotoxicity discontinued cART temporarily or shifted NVP to efavirenz. Conclusions NVP related hepatotoxicity was common among ARV naive HIV infected subjects in our cohort. Baseline ALT elevation and HCV co-infection were associated statistically with the development of hepatotoxicity. Hepatotoxicity led to discontinuing cART temporarily or switching to other regimens in some subjects. It suggested that NVP should be used with caution in patients co-infected with HCV among whom anti-HCV therapy before cART initiation may contribute to minimizing the probability of NVP associated hepatotoxicity.

  20. Incidence and predictors of first line antiretroviral regimen modification in western Kenya.

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    Seth Inzaule

    Full Text Available BACKGROUND: Limited antiretroviral treatment regimens in resource-limited settings require long-term sustainability of patients on the few available options. We evaluated the incidence and predictors of combined antiretroviral treatment (cART modifications, in an outpatient cohort of 955 patients who initiated cART between January 2009 and January 2011 in western Kenya. METHODS: cART modification was defined as either first time single drug substitution or switch. Incidence rates were determined by Poisson regression and risk factor analysis assessed using multivariate Cox regression modeling. RESULTS: Over a median follow-up period of 10.7 months, 178 (18.7% patients modified regimens (incidence rate (IR; 18.6 per 100 person years [95% CI: 16.2-21.8]. Toxicity was the most common cited reason (66.3%. In adjusted multivariate Cox piecewise regression model, WHO disease stage III/IV (aHR; 1.82, 95%CI: 1.25-2.66, stavudine (d4T use (aHR; 2.21 95%CI: 1.49-3.30 and increase in age (aHR; 1.02, 95%CI: 1.0-1.04 were associated with increased risk of treatment modification within the first year post-cART. Zidovudine (AZT and tenofovir (TDF use had a reduced risk for modification (aHR; 0.60 95%CI: 0.38-0.96 and aHR; 0.51 95%CI: 0.29-0.91 respectively. Beyond one year of treatment, d4T use (aHR; 2.75, 95% CI: 1.25-6.05, baseline CD4 counts ≤350 cells/mm3 (aHR; 2.45, 95%CI: 1.14-5.26, increase in age (aHR; 1.05 95%CI: 1.02-1.07 and high baseline weight >60kg aHR; 2.69 95% CI: 1.58-4.59 were associated with risk of cART modification. CONCLUSIONS: Early treatment initiation at higher CD4 counts and avoiding d4T use may reduce treatment modification and subsequently improve sustainability of patients on the available limited options.

  1. Evaluation of multiple measures of antiretroviral adherence in the Eastern European country of Georgia

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    Nikoloz Chkhartishvili

    2014-04-01

    Full Text Available Introduction: There is little information on adherence to antiretroviral therapy (ART in the Eastern European region. This prospective study evaluated multiple measures of adherence and their association with viral suppression among HIV patients in Georgia. Methods: A prospective cohort study enrolled 100 consecutive antiretroviral-naïve adult (age ≥18 years patients, who were followed for three months. Adherence was assessed by medication refill and three self-report measures (an AIDS Clinical Trial Group [ACTG] tool for four-day adherence, a visual analogue scale [VAS] and a rating task for 30-day adherence. The VAS represented a line anchored by 0 and 100% corresponding to the percentage of prescribed doses taken. The rating task asked patients to rate their ability to take all medications as prescribed, with responses categorized into six levels of adherence: very poor (0%, poor (20%, fair (40%, good (60%, very good (80% and excellent (100%. Patients with adherence of ≥95% by medication refill, ACTG and VAS, and ≥80% by rating task, were defined as adherent. Results: Of 100 patients enrolled, eight had missing data and were excluded from analysis. Among the remaining 92 patients, the median age was 39 years, and 70% were men. Major modes of HIV acquisition were injection drug use (IDU; 47.3% and heterosexual contact (44.1%. The proportions of adherent patients were as follows: 68% by medication refill, 90% by ACTG questionnaire, 38% by VAS and 42% by rating task. On average, four months after commencing ART, 52 (56.5% patients had a viral load <400 copies/ml and 26 (28.3% patients had a viral load <50 copies/ml. Of 43 persons with a history of IDU, 22 (51.2% reached a viral load of <400 copies/ml. In multivariate analysis, only refill adherence was a statistically significant predictor of viral suppression of <400 copies/ml: the risk ratio was 1.7 (95% CI: 1.1–2.8. Refill adherence, VAS and rating task were associated with viral

  2. Adjudicated morbidity and mortality outcomes by age among individuals with HIV infection on suppressive antiretroviral therapy.

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    Christopher J Miller

    Full Text Available BACKGROUND: Non-AIDS conditions such as cardiovascular disease and non-AIDS defining cancers dominate causes of morbidity and mortality among persons with HIV on suppressive combination antiretroviral therapy. Accurate estimates of disease incidence and of risk factors for these conditions are important in planning preventative efforts. METHODS: With use of medical records, serious non-AIDS events, AIDS events, and causes of death were adjudicated using pre-specified criteria by an Endpoint Review Committee in two large international trials. Rates of serious non-AIDS which include cardiovascular disease, end-stage renal disease, decompensated liver disease, and non-AIDS cancer, and other serious (grade 4 adverse events were determined, overall and by age, over a median follow-up of 4.3 years for 3,570 participants with CD4+ cell count ≥300 cells/mm³ who were taking antiretroviral therapy and had an HIV RNA level ≤500 copies/mL. Cox models were used to examine the effect of age and other baseline factors on risk of a composite outcome of all-cause mortality, AIDS, or serious non-AIDS. RESULTS: Five-year Kaplan-Meier estimates of the composite outcome, overall and by age were 8.3% (overall, 3.6% (<40, 8.7% (40-49 and 16.1% (≥50, respectively (p<0.001. In addition to age, smoking and higher levels of interleukin-6 and D-dimer were significant predictors of the composite outcome. The composite outcome was dominated by serious non-AIDS events (overall 65% of 277 participants with a composite event. Most serious non-AIDS events were due to cardiovascular disease and non-AIDS cancers. CONCLUSIONS: To date, few large studies have carefully collected data on serious non-AIDS outcomes. Thus, reliable estimates of event rates are scarce. Data cited here, from a geographically diverse cohort, will be useful for planning studies of interventions aimed at reducing rates of serious non-AIDS events among people with HIV.

  3. Trends and economic stress: a challenge to universal access to antiretroviral treatment in India.

    Science.gov (United States)

    Dhamija, P; Bansal, D; Medhi, B

    2009-07-01

    The prospects for expanded access to antiretroviral therapy (ART) in resource-poor settings have greatly improved as a result of global and national efforts to reduce the cost of antiretroviral drugs (ARV), growing availability of cheaper generics, and increased financing available from the Global Funds like Medicines Sans Frontieres. Indian health set-up provides drugs free-of-cost to HIV infected patients through government network and also through open-market to those who intend to have personalized care. Post-2005, implementation of WTO agreement on TRIPS is expected to have a significant impact on pricing and availability of generic ARV. The study has been planned to explore the trends and gaps in availability & accessibility of ARV in India. The trends in per-patient-per-year (PPPY) cost of individual ARV and treatment regimes were also explored. The epidemiological data demonstrated stabilization of the epidemic in India. Most ARV are available in India by the generic manufacturers with a median drug lag period of 2.05 years (Range 0.75-6.51 years). There is a significant price difference in drugs available from generic and originator companies. Prices for patented and generic ARV in India reflect price negotiations that have taken place since the introduction of drugs in the country, still most of the ARVs are available at a much higher cost in the market [median 2.6 times (range 1-7)]. The per-patient per year (PPPY) cost of providing first-line regime in 2008 has decreased 2.75 times from that in 2003. The analysis shows the stabilization of prices of all drugs after 2006. HIV spending in India has seen a growth of 26 percent and 28 percent in 2005-06 and 2006-07 respectively. Still, the expected expenditure to cover the whole patient population needing therapy is considerably higher than the actual expenditure incurred for providing ARV. Despite the price reductions and availability of ARV at a lower cost through agencies like MSF, there is a large gap

  4. Sensorimotor gating and habituation in antipsychotic-naive, first-episode schizophrenia patients before and after 6 months' treatment with quetiapine

    DEFF Research Database (Denmark)

    Aggernaes, Bodil; Glenthøj, Birte Yding; Ebdrup, Bjorn H;

    2010-01-01

    of the human startle reflex in a large group of antipsychotic-naive, first-episode schizophrenia patients, and the effect of subsequent treatment with quetiapine. Thirty-four antipsychotic-naive, first-episode schizophrenia patients (24 males, 10 females), and age- and gender-matched healthy controls were......Impaired prepulse inhibition of the startle reflex (PPI) in schizophrenia has been replicated in many studies. However, previous results may have been influenced by course of illness, and antipsychotic medication. Studies on antipsychotic-naive, first-episode schizophrenia patients are lacking...

  5. The Impact of Non-Antiretroviral Polypharmacy on the Continuity of Antiretroviral Therapy (ART) Among HIV Patients.

    Science.gov (United States)

    Krentz, Hartmut B; Gill, M John

    2016-01-01

    Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy.

  6. Mystery Person

    Science.gov (United States)

    O'Brien, Tom

    2011-01-01

    This article features a mathematical game called "Mystery Person." The author describes how the Mystery Person game was tried with first-graders [age 6]. The Mystery games involve the generation of key questions, the coordination of information--often very complex information--and the formulation of consequences based on this…

  7. Training needs assessment for clinicians at antiretroviral therapy clinics: evidence from a national survey in Uganda

    Directory of Open Access Journals (Sweden)

    Namagala Elizabeth

    2009-08-01

    Full Text Available Abstract Background To increase access to antiretroviral therapy in resource-limited settings, several experts recommend "task shifting" from doctors to clinical officers, nurses and midwives. This study sought to identify task shifting that has already occurred and assess the antiretroviral therapy training needs among clinicians to whom tasks have shifted. Methods The Infectious Diseases Institute, in collaboration with the Ugandan Ministry of Health, surveyed health professionals and heads of antiretroviral therapy clinics at a stratified random sample of 44 health facilities accredited to provide this therapy. A sample of 265 doctors, clinical officers, nurses and midwives reported on tasks they performed, previous human immunodeficiency virus training, and self-assessment of knowledge of human immunodeficiency virus and antiretroviral therapy. Heads of the antiretroviral therapy clinics reported on clinic characteristics. Results Thirty of 33 doctors (91%, 24 of 40 clinical officers (60%, 16 of 114 nurses (14% and 13 of 54 midwives (24% who worked in accredited antiretroviral therapy clinics reported that they prescribed this therapy (p Conclusion Training initiatives should be an integral part of the support for task shifting and ensure that antiretroviral therapy is used correctly and that toxicity or drug resistance do not reverse accomplishments to date.

  8. Naive theories of intelligence and the role of processing fluency in perceived comprehension.

    Science.gov (United States)

    Miele, David B; Molden, Daniel C

    2010-08-01

    Previous research overwhelmingly suggests that feelings of ease people experience while processing information lead them to infer that their comprehension is high, whereas feelings of difficulty lead them to infer that their comprehension is low. However, the inferences people draw from their experiences of processing fluency should also vary in accordance with their naive theories about why new information might be easy or difficult to process. Five experiments that involved reading novel texts showed that participants who view intelligence as a fixed attribute, and who tend to interpret experiences of processing difficulty as an indication that they are reaching the limits of their ability, reported lower levels of comprehension as fluency decreased. In contrast, participants who view intelligence as a malleable attribute that develops through effort, and who do not tend to interpret experiences of processing difficulty as pertaining to some innate ability, did not report lower levels of comprehension as fluency decreased. In fact, when these participants were particularly likely to view effort as leading to increased mastery, decreases in fluency led them to report higher levels of comprehension.

  9. Neisseria lactamica selectively induces mitogenic proliferation of the naive B cell pool via cell surface Ig.

    Science.gov (United States)

    Vaughan, Andrew T; Brackenbury, Louise S; Massari, Paola; Davenport, Victoria; Gorringe, Andrew; Heyderman, Robert S; Williams, Neil A

    2010-09-15

    Neisseria lactamica is a commensal bacteria that colonizes the human upper respiratory tract mucosa during early childhood. In contrast to the closely related opportunistic pathogen Neisseria meningitidis, there is an absence of adaptive cell-mediated immunity to N. lactamica during the peak age of carriage. Instead, outer membrane vesicles derived from N. lactamica mediate a B cell-dependent proliferative response in mucosal mononuclear cells that is associated with the production of polyclonal IgM. We demonstrate in this study that this is a mitogenic human B cell response that occurs independently of T cell help and any other accessory cell population. The ability to drive B cell proliferation is a highly conserved property and is present in N. lactamica strains derived from diverse clonal complexes. CFSE staining of purified human tonsillar B cells demonstrated that naive IgD(+) and CD27(-) B cells are selectively induced to proliferate by outer membrane vesicles, including the innate CD5(+) subset. Neither purified lipooligosaccharide nor PorB from N. lactamica is likely to be responsible for this activity. Prior treatment of B cells with pronase to remove cell-surface Ig or treatment with BCR-specific Abs abrogated the proliferative response to N. lactamica outer membrane vesicles, suggesting that this mitogenic response is dependent upon the BCR.

  10. Clinical role of obinutuzumab in the treatment of naive patients with chronic lymphocytic leukemia

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    Cerquozzi S

    2015-02-01

    Full Text Available Sonia Cerquozzi,1 Carolyn Owen2 1Department of Hematology, University of Calgary, 2Department of Hematology, Tom Baker Cancer Centre, Calgary, AB, Canada Abstract: The introduction of targeted therapy against CD20+ with the monoclonal antibody rituximab has dramatically improved the survival of B-cell non-Hodgkin lymphoma including chronic lymphocytic leukemia (CLL/small lymphocytic lymphoma. Unfortunately, CLL remains incurable with chemoimmunotherapy, with many patients having refractory or relapsing disease after rituximab-containing therapy. Obinutuzumab (GA101 is a novel humanized Type II anti-CD20 monoclonal antibody that has been investigated and compared to rituximab. Here, we provide an overview of obinutuzumab, including its mechanisms of action, preclinical data, and Phase I to III clinical studies. Preclinical data illustrate obinutuzumab's higher potency compared to rituximab through antibody-dependent cellular cytotoxicity and direct cell death. Recently, the CLL11 study presented a significant benefit from obinutuzumab chemoimmunotherapy and supports its use for treatment-naive unfit CLL patients. Herein, we review that obinutuzumab is both a safe and effective alternative to rituximab. Keywords: CLL, GA101, antibody, CD20 

  11. A Naive Glance to Postmodern Architecture in 21st Century: Termination or Transformation?

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    Lerzan ARAS

    2015-06-01

    Full Text Available Too many years have past since Venturi’s Las Vegas analysis. Our taste, point of views, and of course our societal structure has changed. Gene Roddenberry’s cult TV series Star Trek which remained years on screen, turned out to be naive, and charming but also deficient for us. Communication channels have been increased. Technology’s rapid progress has surprised even itself. Lyotard’s analysis about postmodern conditions, or Hassan’s renewed descriptions about postmodernism should be moved to another dimension. As Hassan speaks, "... Postmodernism became more than an artistic style or historical trend or Zeitgeist, it is a way of reading all our signs under the mandate of misprision." (Hassan, 2003 For some critics, the postmodern architecture is about to come to a ‘cul de sac’ while we are experiencing the first quarter of the 21st century. But the matter for question is, whether the postmodern architecture is undergoing a transformation, or the point at issue is a termination. This study aims to evaluate postmodern architecture at this threshold after a short reminder of the past.

  12. Sentiment Analysis of Movie Reviews using Hybrid Method of Naive Bayes and Genetic Algorithm

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    M.Govindarajan

    2013-12-01

    Full Text Available The area of sentiment mining (also called sentiment extraction, opinion mining, opinion extraction, sentiment analysis, etc. has seen a large increase in academic interest in the last few years. Researchers in the areas of natural language processing, data mining, machine learning, and others have tested a variety of methods of automating the sentiment analysis process. In this research work, new hybrid classification method is proposed based on coupling classification methods using arcing classifier and their performances are analyzed in terms of accuracy. A Classifier ensemble was designed using Naive Bayes (NB, Genetic Algorithm (GA. In the proposed work, a comparative study of the effectiveness of ensemble technique is made for sentiment classification. The ensemble framework is applied to sentiment classification tasks, with the aim of efficiently integrating different feature sets and classification algorithms to synthesize a more accurate classification procedure. The feasibility and the benefits of the proposed approaches are demonstrated by means of movie review that is widely used in the field of sentiment classification. A wide range of comparative experiments are conducted and finally, some in-depth discussion is presented and conclusions are drawn about the effectiveness of ensemble technique for sentiment classification.

  13. A Naive Bayes machine learning approach to risk prediction using censored, time-to-event data.

    Science.gov (United States)

    Wolfson, Julian; Bandyopadhyay, Sunayan; Elidrisi, Mohamed; Vazquez-Benitez, Gabriela; Vock, David M; Musgrove, Donald; Adomavicius, Gediminas; Johnson, Paul E; O'Connor, Patrick J

    2015-09-20

    Predicting an individual's risk of experiencing a future clinical outcome is a statistical task with important consequences for both practicing clinicians and public health experts. Modern observational databases such as electronic health records provide an alternative to the longitudinal cohort studies traditionally used to construct risk models, bringing with them both opportunities and challenges. Large sample sizes and detailed covariate histories enable the use of sophisticated machine learning techniques to uncover complex associations and interactions, but observational databases are often 'messy', with high levels of missing data and incomplete patient follow-up. In this paper, we propose an adaptation of the well-known Naive Bayes machine learning approach to time-to-event outcomes subject to censoring. We compare the predictive performance of our method with the Cox proportional hazards model which is commonly used for risk prediction in healthcare populations, and illustrate its application to prediction of cardiovascular risk using an electronic health record dataset from a large Midwest integrated healthcare system.

  14. Naive Treg-like CCR7(+) mononuclear cells indicate unfavorable prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    Shi, Jie-Yi; Duan, Meng; Sun, Qi-Man; Yang, Liuxiao; Wang, Zhi-Chao; Mynbaev, Ospan A; He, Yi-Feng; Wang, Ling-Yan; Zhou, Jian; Tang, Qi-Qun; Cao, Ya; Fan, Jia; Wang, Xiao-Ying; Gao, Qiang

    2016-07-01

    Chemokine receptor-like 1 (CCRL1) has the potential in creating a low level of CCL19 and CCL21 to hinder CCR7(+) cell tracking to tumor tissue. Previously, we found a tumor suppressive role of CCRL1 by impairing CCR7-related chemotaxis of tumor cells in human hepatocellular carcinoma (HCC). Here, we reported a contribution of CCR7(+) mononuclear cells in the tumor microenvironment to the progression of disease. Immunohistochemistry was used to investigate the distribution and clinical significance of CCR7(+) cells in a cohort of 240 HCC patients. Furthermore, the phenotype, composition, and functional status of CCR7(+) cells were determined by flow cytometry, immunofluorescence, and in vitro co-culture assays. We found that CCR7(+) mononuclear cells were dispersed around tumor tissue and negatively related to tumoral expression of CCRL1 (P CCR7(+) mononuclear cells positively correlated with the absence of tumor capsule, vascular invasion, and poor differentiation (P CCR7(+) mononuclear cells was significantly associated with worse survival and increased recurrence. We found that CCR7(+) mononuclear cells featured a naive Treg-like phenotype (CD45RA(+)CD25(+)FOXP3(+)) and possessed tumor-promoting potential by producing TGF-β1. Moreover, CCR7(+) cells were also composed of several immunocytes, a third of which were CD8(+) T cells. CCR7(+) Treg-like cells facilitate tumor growth and indicate unfavorable prognosis in HCC patients, but fortunately, their tracking to tumor tissue is under the control of CCRL1.

  15. Stateless Malware Packet Detection by Incorporating Naive Bayes with Known Malware Signatures

    Directory of Open Access Journals (Sweden)

    Ismahani Ismail

    2014-01-01

    Full Text Available Malware detection done at the network infrastructure level is still an open research problem ,considering the evolution of malwares and high detection accuracy needed to detect these threats. Content based classification techniques have been proven capable of detecting malware without matching for malware signatures. However, the performance of the classification techniques depends on observed training samples. In this paper, a new detection method that incorporates Snort malware signatures into Naive Bayes model training is proposed. Through experimental work, we prove that the proposed work results in low features search space for effective detection at the packet level. This paper also demonstrates the viability of detecting malware at the stateless level (using packets as well as at the stateful level (using TCP byte stream. The result shows that it is feasible to detect malware at the stateless level with similar accuracy to the stateful level, thus requiring minimal resource for implementation on middleboxes. Stateless detection can give a better protection to end users by detecting malware on middleboxes without having to reconstruct stateful sessions and before malwares reach the end users.

  16. Liver-related deaths among persons infected with the human immunodeficiency virus: The D:A:D Study

    DEFF Research Database (Denmark)

    Weber, R; Sabin, CA; Friis-Møller, Nina;

    2006-01-01

    BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. METHODS: We investigated the frequency of and risk factors associated with liver-related de...

  17. Using naive Bayes classifier for classification of convective rainfall intensities based on spectral characteristics retrieved from SEVIRI

    Indian Academy of Sciences (India)

    Slimane Hameg; Mourad Lazri; Soltane Ameur

    2016-07-01

    This paper presents a new algorithm to classify convective clouds and determine their intensity, based oncloud physical properties retrieved from the Spinning Enhanced Visible and Infrared Imager (SEVIRI).The convective rainfall events at 15 min, 4 × 5 km spatial resolution from 2006 to 2012 are analysed overnorthern Algeria. The convective rain classification methodology makes use of the relationship betweencloud spectral characteristics and cloud physical properties such as cloud water path (CWP), cloudphase (CP) and cloud top height (CTH). For this classification, a statistical method based on ‘naiveBayes classifier’ is applied. This is a simple probabilistic classifier based on applying ‘Bayes’ theoremwith strong (naive) independent assumptions. For a 9-month period, the ability of SEVIRI to classifythe rainfall intensity in the convective clouds is evaluated using weather radar over the northern Algeria.The results indicate an encouraging performance of the new algorithm for intensity differentiation ofconvective clouds using SEVIRI data.

  18. Analysis of the evolution of direct costs of antiretroviral delivery in Argentina

    Directory of Open Access Journals (Sweden)

    E Bissio

    2012-11-01

    Full Text Available Background: In Argentina, antiretroviral treatment (ART is covered by the State for all the persons who do not have health insurances, who represent 70% of all HIV infected patients in the country. Since 1992, the Direction of Aids (Ministry of Health buys and delivers ART, treatments for opportunistic infections and reagents to diagnose and follow-up HIV infection. Nevertheless, until now, an analysis of the evolution of the costs of the drugs acquired by the Direction of Aids has not been performed. The aim of this study was to analyze the direct costs of ART for the Direction of Aids in Argentina since 2006, and evaluate progression over time. Methods: The expenditure on ART and drugs for opportunistic infections was obtained. All values (in pesos were converted to dollars. The cost of ART per patient per year was calculated. Changes in cost were determined for the total and per patient expenditures, and the reasons for the changes analyzed. Results: Total expenditure for ART (in uS dollars went from 33.7 million in 2006 to 75 million in 2011 (123% increase. The number of patients on ART covered by the Aids Direction increased from 23228 in 2006 to 33279 (43% by the end of 2011. The cost (u$s of ART per person per year was: *06*: 1449; *07*: 1645; *08*: 1516; *09*: 1543; *10*: 1968; *11*: 2255. This represents a 56% increase from 2006 to 2011, though this change was uneven through the years. This was driven mainly by a decrease from 07 to 08, due to lack of acquisition of ART for political reasons; and a very steep increase in 09-10 due to incorporation of more expensive drugs such as tenofovir/emtricitabine, raltegravir and maraviroc. Conclusions: Annual cost of ART per person in Argentina has been increasing considerably in the last years. Even though this cost is much lower than those informed by some European countries (Italy: u$ 7500[1]; UK: u$ 9000[2], Germany: u$ 18000; it is one of the highest in Latin-America, where median cost is u

  19. Risk factors for mortality during antiretroviral therapy in older populations in resource-limited settings

    Directory of Open Access Journals (Sweden)

    Daniel O’Brien

    2016-01-01

    Full Text Available Introduction: An increasing proportion of adult patients initiating antiretroviral therapy (ART in resource-limited settings are aged >50 years. Older populations on ART appear to have heightened risk of death, but little is known about factors influencing mortality in this population. Methods: We performed a retrospective observational multisite cohort study including all adult patients (≥15 years initiating ART between 2003 and 2013 in programmes supported by Médecins Sans Frontières across 12 countries in Asia, Africa and Europe. Patients were stratified into two age groups, >50 years and 15 to 50 years. A Cox proportional hazards model was used to explore factors associated with mortality. Results: The study included 41,088 patients: 2591 (6.3% were aged >50 years and 38,497 (93.7% were aged 15 to 50 years. The mortality rate was significantly higher in the age group >50 years [367 (14.2% deaths; mortality rate 7.67 deaths per 100 person-years (95% confidence interval, CI: 6.93 to 8.50] compared to the age group 15 to 50 years [3788 (9.8% deaths; mortality rate 4.18 deaths per 100 person-years (95% CI: 4.05 to 4.31], p50 age group. WHO Stage 4 conditions were more strongly associated with increased mortality rates in the 15 to 50 age group compared to populations >50 years. WHO Stage 3 conditions were associated with an increased mortality rate in the 15 to 50 age group but not in the >50 age group. Programme region did not affect mortality rates in the >50 age group; however being in an Asian programme was associated with a 36% reduced mortality rate in populations aged 15 to 50 years compared to being in an African programme. There was a higher overall incidence of Stage 3 WHO conditions in people >50 years (12.8/100 person-years compared to those 15 to 50 years (8.1/100 person-years (p50 age groups. Conclusions: Older patients on ART in resource-limited settings have increased mortality rates, but compared to younger populations this

  20. Endothelial cell‐derived angiopoietin‐2 is a therapeutic target in treatment‐naive and bevacizumab‐resistant glioblastoma

    OpenAIRE

    Scholz, Alexander; Harter, Patrick N.; Cremer, Sebastian; Yalcin, Burak H; Gurnik, Stefanie; Yamaji, Maiko; Di Tacchio, Mariangela; Sommer, Kathleen; Baumgarten, Peter; Bähr, Oliver; Steinbach, Joachim P; Trojan, Jörg; Glas, Martin; Herrlinger, Ulrich; Krex, Dietmar

    2015-01-01

    Abstract Glioblastoma multiforme (GBM) is treated by surgical resection followed by radiochemotherapy. Bevacizumab is commonly deployed for anti‐angiogenic therapy of recurrent GBM; however, innate immune cells have been identified as instigators of resistance to bevacizumab treatment. We identified angiopoietin‐2 (Ang‐2) as a potential target in both naive and bevacizumab‐treated glioblastoma. Ang‐2 expression was absent in normal human brain endothelium, while the highest Ang‐2 levels were ...

  1. Orexin mediates initiation of sexual behavior in sexually naive male rats, but is not critical for sexual performance.

    Science.gov (United States)

    Di Sebastiano, Andrea R; Yong-Yow, Sabrina; Wagner, Lauren; Lehman, Michael N; Coolen, Lique M

    2010-08-01

    The hypothalamic neuropeptide orexin mediates arousal, sleep, and naturally rewarding behaviors, including food intake. Male sexual behavior is altered by orexin receptor-1 agonists or antagonists, suggesting a role for orexin-A in this naturally rewarding behavior. However, the specific role of endogenous orexin-A or B in different elements of male sexual behavior is currently unclear. Therefore, the current studies utilized markers for neural activation and orexin cell-specific lesions to test the hypothesis that orexin is critical for sexual motivation and performance in male rats. First, cFos expression in orexin neurons was demonstrated following presentation of a receptive or non-receptive female without further activation by different elements of mating. Next, the functional role of orexin was tested utilizing orexin-B conjugated saporin, resulting in orexin cell body lesions in the hypothalamus. Lesions were conducted in sexually naive males and subsequent sexual behavior was recorded during four mating trials. Lesion males showed shortened latencies to mount and intromit during the first, but not subsequent mating trials, suggesting lesions facilitated initiation of sexual behavior in sexually naive, but not experienced males. Likewise, lesions did not affect sexual motivation in experienced males, determined by runway tests. Finally, elevated plus maze tests demonstrated reduced anxiety-like behaviors in lesioned males, supporting a role for orexin in anxiety associated with initial exposure to the female in naive animals. Overall, these findings show that orexin is not critical for male sexual performance or motivation, but may play a role in arousal and anxiety related to sexual behavior in naive animals.

  2. Direct-to-consumer advertisements for HIV antiretroviral medications: a progress report.

    Science.gov (United States)

    Kallen, Alexander; Woloshin, Steven; Shu, Jennifer; Juhl, Ellen; Schwartz, Lisa

    2007-01-01

    Direct-to-consumer (DTC) prescription drug advertisements for HIV anti-retrovirals are controversial and have been criticized in the past for including deceptive images and underplaying HIV drug limitations. We sought to describe the state of recent DTC ads for HIV antiretrovirals in popular magazines by performing a content analysis of all complete DTC ads for antiretroviral medications appearing in eight national magazines during a one-year period. Current ads appear to have addressed previous concerns, but important problems still exist, such as failing to specify the medication's role in current treatment, to quantify drug efficacy, or to highlight life-threatening side effects.

  3. Distal sensory polyneuropathy in human immunodeficiency virus patients and nucleoside analogue antiretroviral agents

    Directory of Open Access Journals (Sweden)

    Jose Jimmy

    2007-01-01

    Full Text Available Distal sensory polyneuropathy, which occur commonly in human immunodeficiency virus (HIV patients can occur as a consequence of the disease itself or the antiretroviral treatment the patient is receiving. Among the antiretroviral agents, nucleoside analogues are commonly associated with neuropathy and the main underlying mechanism is thought to be the mitochondrial toxicity exhibited by these agents. Clinical presentation of antiretroviral induced neuropathy is similar to that associated with the HIV infection and in many patients they may overlap. Treatment is primarily symptomatic and certain pathogenesis-based approaches have shown promising results.

  4. CD4 count and viral load specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

    Directory of Open Access Journals (Sweden)

    A Mocroft

    2012-11-01

    Full Text Available Background CD4 and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or negatively affect the risk of disease this would not be identified prior to licensing. The aims of this study were to investigate the CD4 and viral load specific rates of fatal and non-fatal AIDS and non-AIDS events according to current antiretrovirals. Methods Poisson regression was used to compare overall events (fatal or non-fatal AIDS, non-AIDS or death, AIDS events (fatal and non-fatal or non-AIDS events (fatal or non-fatal for specific nucleoside pairs and third drugs used with>1000 person-years of follow-up (PYFU after January 1st 2001. Results 9801 patients were included. The median baseline date was January 2004 (interquartile range [IQR] January 2001–February 2007, age was 40.4 (IQR 34.6–47.3 years, and time since starting cART was 3.3 (IQR 0.9–5.1 years. At baseline, the median nadir CD4 was 162 (IQR 71–257/mm3, baseline CD4 was 390 (IQR 249–571/mm3, viral load was 1.9 (IQR 1.7–3.3 log10copies/ml and 2961 (30.2% had a prior AIDS diagnosis and 6.4 years prior to baseline. During 42372.5 PYFU, 1203 (437 AIDS and 766 non-AIDS events occurred. The overall event rate was 2.8 per 100 PYFU (95% confidence interval [CI] 2.7–3.0, of AIDS events was 1.0 (95% CI 0.9–1.1 and of non-AIDS events was 1.8 (95% CI 1.7–1.9. Of the AIDS events, 53 (12.1%were fatal as were 239 (31.2% of the non-AIDS events. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global p-value=0.084, and third drugs (global p-value=0.031. Compared to zidovudine/lamivudine, patients taking abacavir/lamivudine (adjusted incidence rate ratio [aIRR] 1.22; 95% CI 0.99–1.49 and abacavir plus one other nucleoside (aIRR 1.51; 95% CI 1.14–2.02 had an increased incidence of overall events. Comparing the third drugs

  5. Comparing antiretroviral treatment outcomes between a prospective community-based and hospital-based cohort of HIV patients in rural Uganda

    Directory of Open Access Journals (Sweden)

    Alibhai Arif

    2011-11-01

    Full Text Available Abstract Background Improved availability of antiretroviral therapy in sub-Saharan Africa is intended to benefit all eligible HIV-infected patients; however in reality antiretroviral services are mainly offered in urban hospitals. Poor rural patients have difficulty accessing the drugs, making the provision of antiretroviral therapy inequitable. Initial tests of community-based treatment programs in Uganda suggest that home-based treatment of HIV/AIDS may equal hospital-based treatment; however the literature reveals limited experiences with such programs. The research This intervention study aimed to; 1 assess the effectiveness of a rural community-based ART program in a subcounty (Rwimi of Uganda; and 2 compare treatment outcomes and mortality in a rural community-based antiretroviral therapy program with a well-established hospital-based program. Ethics approvals were obtained in Canada and Uganda. Results and outcomes Successful treatment outcomes after two years in both the community and hospital cohorts were high. All-cause mortality was similar in both cohorts. However, community-based patients were more likely to achieve viral suppression and had good adherence to treatment. The community-based program was slightly more cost-effective. Per capita costs in both settings were unsustainable, representing more than Uganda’s Primary Health Care Services current expenditures per person per year for all health services. The unpaid community volunteers showed high participation and low attrition rates for the two years that this program was evaluated. Challenges and successes Key successes of this study include the demonstration that antiretroviral therapy can be provided in a rural setting, the creation of a research infrastructure and culture within Kabarole’s health system, and the establishment of a research collaboration capable of enriching the global health graduate program at the University of Alberta. Challenging questions about the

  6. Nonspecific Effect of Stress on Brain Gray Matter Volume in Drug-naive Female Patients with First Depressive Episode

    Institute of Scientific and Technical Information of China (English)

    Chuan-Jun Zhuo; Hai-Man Bian; Yan-Jie Gao; Xiao-Lei Ma; Sheng-Zhang Ji; Meng-Yuan Yao; Ning Zhai

    2016-01-01

    Background: This study aimed to observe the differences in brain gray matter volume in drug-naive female patients after the first episode of major depression with and without stressful life events (SLEs) before the onset of depression.Methods: Forty-three drug-naive female patients voluntarily participated in the present study after the first major depressive episode.The life event scale was used to evaluate the severity of the impact of SLEs during 6 months before the onset of the major depressive episode.High-field magnetic resonance imaging (MRI) scans were obtained, and the VBM and SPM8 software process were used to process and analyze the MRI.Results: Compared to that in patients without SLEs, the volume of brain gray matter was lower in the bilateral temporal lobe, right occipital lobe, and right limbic lobe in the SLE group.However, the gray matter volume did not differ significantly between the two groups after the application of false discovery rate (FDR) correction.Conclusions: Although the results of the present study suggest the absence of significant differences in brain gray matter volume between female drug-naive patients after the first episode of major depression with and without SLEs after FDR correction, the study provides useful information for exploring the definitive role of stress in the onset of depression.

  7. Personal Competencies in Personalized Learning

    Science.gov (United States)

    Redding, Sam

    2014-01-01

    Personal competencies--cognitive, metacognitive, motivational, and social/emotional--are applied by students in learning (mastery of knowledge and skills). These competencies are both acquired through learning and applied in the learning process. Personalized learning--a promising approach to education made practical by advances in…

  8. Mortality of HIV-infected patients starting antiretroviral therapy in sub-Saharan Africa: comparison with HIV-unrelated mortality.

    Directory of Open Access Journals (Sweden)

    Martin W G Brinkhof

    2009-04-01

    Full Text Available BACKGROUND: Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa. METHODS AND FINDINGS: Patients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs with 95% confidence intervals (CIs. Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67% patients were female, and 10,811 of 12,720 patients (85% with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1 per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO stage III/IV, compared to 1.00 (0.55-1.81 per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6 and 3.44 (1.91-6.17. Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94 per 100 person-years and the SMR was 1.14 (0.47-2.77. CONCLUSIONS: Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the

  9. HIV entry inhibitors: a new generation of antiretroviral drugs

    Institute of Scientific and Technical Information of China (English)

    Elias KRAMBOVITIS; Filippos PORICHIS; Demetrios A SPANDIDOS

    2005-01-01

    AIDS is presently treatable, and patients can have a good prognosis due to the success of highly active antiretroviral therapy (HAART), but it is still not curable or preventable. High toxicity of HAART, and the emergence of drug resistance add to the imperative to continue research into new strategies and interventions.Considerable progress in the understanding of HIV attachment and entry into host cells has suggested new possibilities for rationally designing agents that interfere with this process. The approval and introduction of the fusion inhibitor enfuvirtide (Fuzeon) for clinical use signals a new era in AIDS therapeutics. Here we review the crucial steps the virus uses to achieve cell entry, which merit attention as potential targets, and the compounds at pre-clinical and clinical development stages, reported to effectively inhibit cell entry.

  10. Effects of nutritional supplementation for HIV patients starting antiretroviral treatment

    DEFF Research Database (Denmark)

    Olsen, Mette Frahm; Abdissa, Alemseged; Kæstel, Pernille

    2014-01-01

    Objectives: To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months...... delay. Design: Randomised controlled trial. Setting: Three public ART facilities in Jimma, Oromia region, Ethiopia. Participants: Adults with HIV eligible for ART with body mass index (BMI) >16. Intervention: Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either...... and CD3 and CD8 counts. Results: Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg...

  11. Preferred antiretroviral drugs for the next decade of scale up

    Directory of Open Access Journals (Sweden)

    Isabelle Andrieux-Meyer

    2012-09-01

    Full Text Available Global commitments aim to provide antiretroviral therapy (ART to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings.

  12. Antiretroviral therapy-induced Leber’s hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Anand Moodley

    2014-05-01

    Full Text Available Optic neuropathy in HIV-infected patients results from the HIV infection itself, post-infectious auto-immune disease, opportunistic infections and drugs. Nucleoside reverse transcriptase inhibitors (NRTIs such as zidovudine and stavudine have known mitochondrial toxicity and can cause mitochondrial myopathies, neuropathies, hyperlactataemia, and can induce mitochondrial genetic disorders. Individuals with the mutation for Leber’s hereditary optic neuropathy (LHON, a mitochondrial disorder, are usually asymptomatic but develop visual loss when exposed to external triggers such as smoking. We report on two HIV-infected patients with LHON mutations (m.14484T>C and m.11778G>A who developed profound visual loss with antiretroviral therapy. We postulate that the phenotypic expression of LHON in these genetically predisposed individuals was triggered by NRTI drugs lamivudine and tenofovir when used in combination, despite their relatively weak mitochondrial toxic effects. 

  13. Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy

    Directory of Open Access Journals (Sweden)

    Kimberly N. Capers

    2011-01-01

    Full Text Available Guillain-Barré syndrome (GBS has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome.

  14. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

    DEFF Research Database (Denmark)

    Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred

    2015-01-01

    BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS: We randomly assigned HIV...... entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients...... per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)....

  15. [Policy dilemmas in providing antiretroviral treatment in Brazil].

    Science.gov (United States)

    do Lago, Regina Ferro; Costa, Nilson do Rosário

    2010-11-01

    This paper addresses institutional constraints that have affected Brazilian politics regarding provision of anti-retroviral treatment (ART) to HIV/Aids patients. We analyzed the normative conflict resulting from international agreements on intellectual property rights, especially patent protection, and the constitutional rights of Brazilian patients to universal and free access to ART. These constraints have not substantially changed the Brazilian public policy yet, but they may impact the future sustainability of this policy. As the main barrier to the production of patented drugs is not technological but institutional, Brazilian government faces a dilemma. It may either abide by existing monopolistic restrictions or it may incite competitiveness of domestic industries and developing countries in the pharmaceutical market.

  16. Early Combination Antiretroviral Therapy Limits HIV-1 Persistence in Children.

    Science.gov (United States)

    Luzuriaga, Katherine

    2016-01-01

    Globally, 240,000 infants are newly infected with HIV-1 each year and 3.2 million children are living with the infection. Combination antiretroviral therapy (cART) has reduced HIV-1-related disease and mortality in children but is not curative owing to the early generation of a latent reservoir of long-lived memory CD4(+) T cells bearing replication-competent HIV-1 provirus integrated into cellular DNA. This review focuses on recent advances in our understanding of the establishment of HIV-1 persistence in children and how early initiation of cART in the setting of the developing infant immune system limits the formation of the long-lived latent CD4(+) cell reservoir that remains a barrier to remission or cure.

  17. Delayed HIV diagnosis and initiation of antiretroviral therapy

    DEFF Research Database (Denmark)

    Lodi, Sara; Dray-Spira, Rosemary; Touloumi, Giota;

    2014-01-01

    OBJECTIVES: In Europe and elsewhere, health inequalities among HIV-positive individuals are of concern. We investigated late HIV diagnosis and late initiation of combination antiretroviral therapy (cART) by educational level, a proxy of socioeconomic position. DESIGN AND METHODS: We used data from...... included individuals diagnosed with HIV between 1996 and 2011, aged at least 16 years, with known educational level and at least one CD4 cell count within 6 months of HIV diagnosis. We examined trends by education level in presentation with advanced HIV disease (AHD) (CD4 ... count at cART initiation was lower with poorer educational level. CONCLUSIONS: Socioeconomic inequalities in delayed HIV diagnosis and initiation of cART are present in European countries with universal healthcare systems and individuals with lower educational level do not equally benefit from timely c...

  18. Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

    Directory of Open Access Journals (Sweden)

    Jacinta Nwamaka Nwogu

    2016-01-01

    Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

  19. Novel antiretroviral drugs and renal function monitoring of HIV patients.

    Science.gov (United States)

    Maggi, Paolo; Montinaro, Vincenzo; Mussini, Cristina; Di Biagio, Antonio; Bellagamba, Rita; Bonfanti, Paolo; Calza, Leonardo; Cherubini, Chiara; Corsi, Paola; Gargiulo, Miriam; Montella, Francesco; Rusconi, Stefano

    2014-01-01

    Chronic kidney disease is a major comorbidity in patients affected by HIV infection. In addition, the introduction of new antiretroviral agents that interact with creatinine transporters is raising some concerns. In this review we analyze the currently available data about three new antiretroviral drugs and one new pharmacokinetic enhancer. Three of them (rilpivirine, cobicistat, dolutegravir) have shown some interactions with renal function, while tenofovir alafenamide fumarate reduces the plasmatic concentration of the parent drug. The future use of tenofovir alafenamide seems to be encouraging in order to reduce the renal interaction of tenofovir. Rilpivirine, cobicistat, and dolutegravir reduce the tubular secretion of creatinine, inducing a decrease of estimated glomerular filtration rate according to creatinine. Rilpivirine and dolutegravir block the uptake of creatinine from the blood, inhibiting organic cation transporter 2, and cobicistat interacts with the efflux inhibiting multidrug and toxin extrusion protein 1. This effect can then be considered a "reset" of the estimated glomerular filtration rate according to creatinine. However, clinicians should carefully monitor renal function in order to identify possible alterations suggestive of a true renal functional impairment. Owing to the interference of these drugs with creatinine secretion, an alternative way of estimation of glomerular filtration rate would be desirable. However, at the moment, other methods of direct glomerular filtration rate measurement have a high impact on the patient, are not readily available, or are not reliable in HIV patients. Consequently, use of classic formulas to estimate glomerular filtration rate is still recommended. Also, tubular function needs to be carefully monitored with simple tests such as proteinuria, phosphatemia, urinary excretion of phosphate, normoglycemic glycosuria, and excretion of uric acid.

  20. Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC).

    Science.gov (United States)

    May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D'Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan A C

    2014-06-01

    The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70,000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org).

  1. Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms.

    Science.gov (United States)

    Ferrari, Luiz F; Levine, Jon D

    2010-09-01

    A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKCε-independent, and alcohol-induced painful neuropathy was PKCε-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKCε-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction.

  2. Antiretroviral therapy outcomes among adolescents and youth in rural Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Helen Bygrave

    Full Text Available Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents 15.1-19 years (adolescents, 19.1-24 years (young adults and 24.1-29.9 years (older adults. Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008. Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35. Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52. This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults.

  3. Use of third line antiretroviral therapy in Latin America.

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    Carina Cesar

    Full Text Available BACKGROUND: Access to highly active antiretroviral therapy (HAART is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. METHODS: Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. RESULTS: Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3% failed a second line regimen and 44 (0.8% received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18-2.00, p = 0.001, younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86-4.10, p<0.001, and prior AIDS (HR = 2.17, 95% CI 1.62-2.90, p<0.001. CONCLUSIONS: Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.

  4. Fanconi Syndrome and Antiretrovirals: It Is Never Too Late.

    Science.gov (United States)

    Luni, Faraz Khan; Khan, Abdur Rahman; Prashar, Rohini; Vetteth, Sandeep; Duggan, Joan M

    2016-01-01

    Antiretroviral medications such as tenofovir have been associated with Fanconi syndrome (FS) usually identified within the first 1-29 months after exposure to the medication. We present a case of life-threatening FS which developed in a 37-year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later, and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3 years before admission for FS. She developed nausea, vomiting, diarrhea, and generalized weakness over a 2-week time period and presented to the hospital. In the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12 mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95 mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by antiretroviral therapy (ART) was suspected and the ART was discontinued with resolution of the renal abnormalities within 7 days. A non-tenofovir-containing ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over the next 8 months, the patient was without recurrence of the FS. This case report demonstrates the acute development of FS after prolonged exposure to tenofovir without exposure to additional nephrotoxins such as nonsteroidal medications or aminoglycosides. Tenofovir can cause FS at any time and should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure.

  5. Personality Disorders

    Science.gov (United States)

    ... for Building a Healthy Self-Image and Improving Self-Esteem 8 Things You Should Know About Body Dysmorphic ... is more of a daydreamer than a practical action taker. Paranoid Personality Disorder. The essential feature for ...

  6. Personal reputation

    DEFF Research Database (Denmark)

    Foste, Elizabeth; Botero, Isabel C.

    2012-01-01

    perceptions of personal reputation and work competence. Participants, acting in the role of supervisors, read one of four scenarios and evaluated a new employee. Results suggest that delivery style and message content independently influence the supervisor’s willingness to grant a request as well as influence...... perceptions of personal reputation, whereas perceptions of work competence are primarily affected by message content. Implications of results for theory and practice are discussed....

  7. Vitamin D supplementation improves sustained virologic response in chronic hepatitis C(genotype 1)-naive patientsaa

    Institute of Scientific and Technical Information of China (English)

    Saif Abu-Mouch; Zvi Fireman; Jacob Jarchovsky; Abdel-Rauf Zeina; Nimer Assy

    2011-01-01

    AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy. METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 μg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin D3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin D. HCV-RNA was assessed by real-time polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment. RESULTS: Clinical characteristics were similar in both groups. The treatment group had a higher mean body mass index (27 ± 4 kg/m2 vs 24 ± 3 kg/m2, P F2: 42% vs 19%, P < 0.001) than the controls. At week 4, 16 (44%) treated patients and 6 (17%) controls were HCV-RNA negative (P < 0.001). At week 12, 34 (94%) treated patients and 17 (48%) controls were HCV-RNA negative (P < 0.001). At 24 wk post-treatment (SVR), 31 (86%) treated patients and 15 (42%) controls were HCV-RNA negative (P < 0.001). Viral load, advanced fibrosis and vitamin D supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin. CONCLUSION: Adding vitamin D to conventional Peg-α-2b/ribavirin therapy for treatment-naive patients with chronic HCV genotype 1 infection significantly improves the viral response.

  8. Learning the Hang Power Clean: Kinetic, Kinematic, and Technical Changes in Four Weightlifting Naive Athletes.

    Science.gov (United States)

    Haug, William B; Drinkwater, Eric J; Chapman, Dale W

    2015-07-01

    The investment in learning required to reach benefit with weightlifting training is currently not well understood in elite athletes. The purpose of this investigation was to quantify changes in vertical jump power production and kinematic variables in hang power clean (HPC) performance during the learning process from a naive state in a multiple single-subject research design. Four elite athletes undertook HPC learning for approximately 20-30 minutes twice per week over a 169-day period. Changes in parameters of vertical power production during squat jump (SJ) and countermovement jump (CMJ) were monitored from baseline (day 0) and at 3 additional occasions. Hang power clean movement kinematics and bar path traces were monitored from day 35 and at 3 additional occasions particular to the individual's periodized training plan. Descriptive statistics were reported within athletes as mean ± SD. We observed a 14.1-35.7% (SJ) and a -14.4 to 20.5% (CMJ) gain in peak power across the 4 jump testing occasions with improvements over the first 4 weeks (SJ: 9.2-32.6%; CMJ: -2.91 to 20.79%). Changes in HPC movement kinematics and barbell path traces occurred for each athlete indicating a more rearward-directed center of pressure over the concentric phase, greater double knee bend during the transition phase, decreased maximal plantar flexion, and minimal vertical displacement of body mass with HPC learning. Considering the minimal investment of 4 weeks to achieve increases in vertical power production, the benefits of training with HPC justified the associated time costs for these 4 elite athletes.

  9. Neurocognitive function in acromegaly after surgical resection of GH-secreting adenoma versus naive acromegaly.

    Directory of Open Access Journals (Sweden)

    Juan Francisco Martín-Rodríguez

    Full Text Available Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH and insulin-like growth factor (IGF-I hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with

  10. An amorphous model for morphological processing in visual comprehension based on naive discriminative learning.

    Science.gov (United States)

    Baayen, R Harald; Milin, Petar; Đurđević, Dusica Filipović; Hendrix, Peter; Marelli, Marco

    2011-07-01

    A 2-layer symbolic network model based on the equilibrium equations of the Rescorla-Wagner model (Danks, 2003) is proposed. The study first presents 2 experiments in Serbian, which reveal for sentential reading the inflectional paradigmatic effects previously observed by Milin, Filipović Đurđević, and Moscoso del Prado Martín (2009) for unprimed lexical decision. The empirical results are successfully modeled without having to assume separate representations for inflections or data structures such as inflectional paradigms. In the next step, the same naive discriminative learning approach is pitted against a wide range of effects documented in the morphological processing literature. Frequency effects for complex words as well as for phrases (Arnon & Snider, 2010) emerge in the model without the presence of whole-word or whole-phrase representations. Family size effects (Moscoso del Prado Martín, Bertram, Häikiö, Schreuder, & Baayen, 2004; Schreuder & Baayen, 1997) emerge in the simulations across simple words, derived words, and compounds, without derived words or compounds being represented as such. It is shown that for pseudo-derived words no special morpho-orthographic segmentation mechanism, as posited by Rastle, Davis, and New (2004), is required. The model also replicates the finding of Plag and Baayen (2009) that, on average, words with more productive affixes elicit longer response latencies; at the same time, it predicts that productive affixes afford faster response latencies for new words. English phrasal paradigmatic effects modulating isolated word reading are reported and modeled, showing that the paradigmatic effects characterizing Serbian case inflection have crosslinguistic scope.

  11. Attentional control and subjective executive function in treatment-naive adults with Attention Deficit Hyperactivity Disorder.

    Directory of Open Access Journals (Sweden)

    Venke Arntsberg Grane

    Full Text Available We investigated performance-derived measures of executive control, and their relationship with self- and informant reported executive functions in everyday life, in treatment-naive adults with newly diagnosed Attention Deficit Hyperactivity Disorder (ADHD; n = 36 and in healthy controls (n = 35. Sustained attentional control and response inhibition were examined with the Test of Variables of Attention (T.O.V.A.. Delayed responses, increased reaction time variability, and higher omission error rate to Go signals in ADHD patients relative to controls indicated fluctuating levels of attention in the patients. Furthermore, an increment in NoGo commission errors when Go stimuli increased relative to NoGo stimuli suggests reduced inhibition of task-irrelevant stimuli in conditions demanding frequent responding. The ADHD group reported significantly more cognitive and behavioral executive problems than the control group on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A. There were overall not strong associations between task performance and ratings of everyday executive function. However, for the ADHD group, T.O.V.A. omission errors predicted self-reported difficulties on the Organization of Materials scale, and commission errors predicted informant reported difficulties on the same scale. Although ADHD patients endorsed more symptoms of depression and anxiety on the Achenbach System of Empirically Based Assessment (ASEBA than controls, ASEBA scores were not significantly associated with T.O.V.A. performance scores. Altogether, the results indicate multifaceted alteration of attentional control in adult ADHD, and accompanying subjective difficulties with several aspects of executive function in everyday living. The relationships between the two sets of data were modest, indicating that the measures represent non-redundant features of adult ADHD.

  12. Attentional control and subjective executive function in treatment-naive adults with Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Grane, Venke Arntsberg; Endestad, Tor; Pinto, Arnfrid Farbu; Solbakk, Anne-Kristin

    2014-01-01

    We investigated performance-derived measures of executive control, and their relationship with self- and informant reported executive functions in everyday life, in treatment-naive adults with newly diagnosed Attention Deficit Hyperactivity Disorder (ADHD; n = 36) and in healthy controls (n = 35). Sustained attentional control and response inhibition were examined with the Test of Variables of Attention (T.O.V.A.). Delayed responses, increased reaction time variability, and higher omission error rate to Go signals in ADHD patients relative to controls indicated fluctuating levels of attention in the patients. Furthermore, an increment in NoGo commission errors when Go stimuli increased relative to NoGo stimuli suggests reduced inhibition of task-irrelevant stimuli in conditions demanding frequent responding. The ADHD group reported significantly more cognitive and behavioral executive problems than the control group on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). There were overall not strong associations between task performance and ratings of everyday executive function. However, for the ADHD group, T.O.V.A. omission errors predicted self-reported difficulties on the Organization of Materials scale, and commission errors predicted informant reported difficulties on the same scale. Although ADHD patients endorsed more symptoms of depression and anxiety on the Achenbach System of Empirically Based Assessment (ASEBA) than controls, ASEBA scores were not significantly associated with T.O.V.A. performance scores. Altogether, the results indicate multifaceted alteration of attentional control in adult ADHD, and accompanying subjective difficulties with several aspects of executive function in everyday living. The relationships between the two sets of data were modest, indicating that the measures represent non-redundant features of adult ADHD.

  13. Use of non-antiretroviral drugs among individuals with and without HIV-infection

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Kronborg, Gitte; Larsen, Carsten S

    2017-01-01

    no injection drug abuse or hepatitis C infection. Population controls were identified from The Danish Civil Registration System and matched on age and gender (5:1). We analyzed the proportion of individuals who redeemed 0-1, 2-4, 5-9, or 10 or more non-antiretroviral drugs. Data were analyzed according......AIM: We investigated the use of non-antiretroviral drugs in the HIV-infected compared to the general population. METHODS: From the Danish HIV Cohort Study, we identified all HIV-infected individuals older than 18 years at HIV diagnosis who received care in Denmark through 1995-2013 and reported...... to calendar time, age, time from initiation of combination antiretroviral therapy (cART) and stratified by gender, geographical origin and route of HIV transmission. We further analyzed the use of the 25 most used non-antiretroviral drug classes. RESULTS: We identified 4,928 HIV-infected individuals (median...

  14. Impact of switching antiretroviral therapy on lipodystrophy and other metabolic complications: a review

    DEFF Research Database (Denmark)

    Hansen, Birgitte R; Haugaard, Steen B; Iversen, Johan;

    2004-01-01

    Following the introduction of highly active antiretroviral therapy (HAART), metabolic and morphological complications known as HIV associated lipodystrophy syndrome (HALS) have been increasingly common. The approaches to target these complications span from resistance exercise, diet and use...

  15. Lessons learned during down referral of antiretroviral treatment in Tete, Mozambique

    Directory of Open Access Journals (Sweden)

    Decroo Tom

    2009-05-01

    Full Text Available Abstract As sub-Saharan African countries continue to scale up antiretroviral treatment, there has been an increasing emphasis on moving provision of services from hospital level to the primary health care clinic level. Delivery of antiretroviral treatment at the clinic level increases the number of entry points to care, while the greater proximity of services encourages retention in care. In Tete City, Mozambique, patients on antiretrovirals were rapidly down referred from a provincial hospital to four urban clinics in large numbers without careful planning, resulting in a number of patients being lost to follow-up. We outline some key lessons learned to support down referral, including the need to improve process management, clinic infrastructure, monitoring systems, and patient preparation. Down referral can be avoided by initiating patients' antiretroviral treatment at clinic level from the outset.

  16. Combination antiretroviral therapy and chronic HIV infection affect serum retinoid concentrations: longitudinal and cross-sectional assessments

    Directory of Open Access Journals (Sweden)

    Loignon Maude

    2012-02-01

    Full Text Available Abstract Background Several lines of evidence suggest that retinoids (retinol-ROL or vitamin A, and its active metabolites, retinoic acids-RAs play important pathogenic roles in HIV infection and combination antiretroviral therapy (cART-related events. We previously reported that antiretrovirals alter RAs synthesis in vitro. We hypothesised that in vivo serum retinoid concentrations are affected by both cART and HIV infection. This might explain several clinical and laboratory abnormalities reported in HIV-infected patients receiving cART. Methods The effects of optimal cART and chronic HIV on serum retinoids were firstly assessed longitudinally in 10 HIV-infected adults (group1 = G1: twice while on optimal cART (first, during long-term and second, during short term cART and twice during 2 cART interruptions when HIV viral load (VL was detectable. Retinoid concentrations during optimal long term cART in G1 were compared with cross-sectional results from 12 patients (G2 with suboptimal cART (detectable VL and from 28 healthy adults (G3. Serum retinoids were measured by HPLC with ultraviolet detection. Retinoid concentrations were correlated with VL, CD4+ T- cell count and percentages, CD8+38+ fluorescence, triglycerides, cholesterol and C-peptide serum levels. Results During optimal cART, G1 participants had drastically reduced RAs (0.5 ± 0.3 μg/dL; P + T- cell count, CD8+38+ fluorescence, VL. ROL correlated with triglycerides and cholesterol in G1 (rs = 0.8; P = 0.01. Conclusions Serum RAs levels are significantly diminished by cART, whereas ROL concentrations significantly decreased during uncontrolled HIV infection but augmented with optimal cART. These alterations in retinoid concentrations may affect the expression of retinoid-responsive genes involved in metabolic, hormonal and immune processes and be responsible for some adverse events observed in HIV-infected persons treated with antiretrovirals. Further studies should assess

  17. PATIENTS ON ANTIRETROVIRAL THERAPY WHO WERE LOST TO FOLLOW-UP AT A TERTIARY CARE HOSPITAL, PUNE, INDIA

    Directory of Open Access Journals (Sweden)

    Dileep B.

    2014-09-01

    Full Text Available Importance: With increasing number of persons living with Human Immunodeficiency Virus (HIV in major cities there is a need to have a comprehensive strategy to reduce the number of drop outs from the anti-retroviral (ART therapy. This can be done effectively only when we study the reasons why patients are lost to follow up. This study has brought to light novel causes of non-adherence to ART, like migration, discordance and resort to alternative therapies. DESIGN: This is a qualitative study conducted at ART Center, Byramjee Jeejeebhoy Medical College (BJMC and Sassoon General Hospital (SGH, Pune, a tertiary referral center in India. We included all those patients who were initiated antiretroviral therapy and lost to follow-up (LFU any time during the entire month after three months during which the appointment was scheduled. All these patients were interviewed during restart of ART, in ART center, BJMC and SGH. MAIN OUTCOMES AND MEASURES: All socio-demographic and clinical factors associated with antiretroviral therapy adherence. RESULTS: Out of a total 51patients lost to follow-up, patients above thirty five years of age and male sex were associated with a higher chance of being lost to LFU. Illiteracy rate was high in age group above 35 years (64.1% and in females. Male drivers were lost to follow-up at a greater extent [14(24.75%]. Out of 24(47.06% married patients, 12(50% male patients were sero-discordant. The chance of defaulting from therapy was high in the first three months and one year later from the initiation of therapy. Migration led to drop out of 13(25.49% patients. Other important factors leading to loss to follow up were: death in family, side effects of drugs and family disturbance. Alcoholism was the cause in 23(45.10% male patients. CONCLUSION AND RELEVANCE: Migration, illiteracy, alcoholism, discordant couples, death in family, low socio-economic status, resorting to alternative therapies were the prominent factors which

  18. Nanoformulated antiretroviral drug combinations extend drug release and antiretroviral responses in HIV-1-infected macrophages: implications for neuroAIDS therapeutics.

    Science.gov (United States)

    Nowacek, Ari S; McMillan, JoEllyn; Miller, Reagan; Anderson, Alec; Rabinow, Barrett; Gendelman, Howard E

    2010-12-01

    We posit that improvements in pharmacokinetics and biodistributions of antiretroviral therapies (ART) for human immunodeficiency virus type one-infected people can be achieved through nanoformulationed drug delivery systems. To this end, we manufactured nanoparticles of atazanavir, efavirenz, and ritonavir (termed nanoART) and treated human monocyte-derived macrophages (MDM) in combination therapies to assess antiretroviral responses. This resulted in improved drug uptake, release, and antiretroviral efficacy over monotherapy. MDM rapidly, within minutes, ingested nanoART combinations, at equal or similar rates, as individual formulations. Combination nanoART ingested by MDM facilitated individual drug release from 15 to >20 days. These findings are noteworthy as a nanoART cell-mediated drug delivery provides a means to deliver therapeutics to viral sanctuaries, such as the central nervous system during progressive human immunodeficiency virus type one infection. The work brings us yet another step closer to realizing the utility of nanoART for virus-infected people.

  19. Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Walter de Araujo Eyer-Silva

    2012-08-01

    Full Text Available Immune reconstitution inflammatory syndrome (IRIS in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

  20. Antiretroviral drug supply challenges in the era of scaling up ART in Malawi

    OpenAIRE

    2011-01-01

    Abstract The number of people receiving antiretroviral treatment (ART) has increased considerably in recent years and is expected to continue to grow in the coming years. A major challenge is to maintain uninterrupted supplies of antiretroviral (ARV) drugs and prevent stock outs. This article discusses issues around the management of ARVs and prevention of stock outs in Malawi, a low-income country with a high HIV/AIDS burden, and a weak procurement and supply chain management system. This sy...

  1. Once-daily antiretroviral therapy in a cohort of HIV-infected children and adolescents.

    Science.gov (United States)

    Jiménez-Montero, Beatriz; Beceiro, José; de José-Gómez, M Isabel; González-Tomé, M Isabel; Gurbindo-Gutierrez, Dolores; Martínez-Pérez, Jorge; Mellado-Peña, M José; Navarro-Gómez, M Luisa; Roa-Francia, Miguel A; Rojo-Conejo, Pablo; Saavedra-Lozano, Jesús; Jiménez de Ory, Santiago; Ramos-Amador, José T

    2014-10-01

    We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.

  2. Common sense, intuition, and theory in personality and social psychology.

    Science.gov (United States)

    Cacioppo, John T

    2004-01-01

    Theoretical work in personality and social psychology benefits from a well-developed understanding of the prior empirical and theoretical work on a problem and from informed intuitions. Intuitions develop about a subject matter through years of study, investigation, and problem solving, just as chess masters develop a sophisticated set of cognitive structures that change the very appearance of the chess board. In part because the subject matter is so personal, students new to personality and social psychology arrive with many intuitions, prior beliefs, and naive theories about social processes and behavior based on unsystematic experiences and observations. These intuitions can hinder or foster theoretical progress. The role of mentors, critiques, and empirical tests in minimizing the deleterious effects of these entry biases is discussed. Refined scientific intuitions are also subject to error, however, so means of minimizing these errors are also discussed.

  3. Cost effectiveness analysis of clinically driven versus routine laboratory monitoring of antiretroviral therapy in Uganda and Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Antonieta Medina Lara

    Full Text Available BACKGROUND: Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART have rarely been evaluated. METHODS: Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779. Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM or laboratory and clinical monitoring (LCM; individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial. RESULTS: 3316 (1660LCM;1656CDM symptomatic, immunosuppressed ART-naive adults (median (IQR age 37 (32,42; CD4 86 (31,139 cells/mm(3 were followed for median 4.9 years. LCM had a mean 0.112 year (41 days survival benefit at an additional mean cost of $765 [95%CI:685,845], translating into an adjusted incremental cost of $7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below $3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks. CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term. CONCLUSIONS: There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low

  4. Screening for Cryptococcal Antigenemia in Anti-Retroviral Naïve AIDS Patients in Benin City, Nigeria

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    Favour Osazuwa

    2012-05-01

    Full Text Available Objectives: Cryptococcus neoformans is the most incriminated fungal pathogen causing meningitis in acquired immune deficiency syndrome (AIDS patients, and is known to constitute a major cause of deaths in AIDS patients. This study thus aimed to determine the baseline sero-prevalence of Cryptococcus neoformans infection in anti-retroviral naïve (ART-naïve AIDS patients using the serum Cryptococcal antigen (crag detection method. Baseline effect of variation in CD4 counts, as well as sex and age with sero-positivity for crag were also determined.Methods: This descriptive cross-sectional study included 150 (61 males and 89 females ART-naïve AIDS patients attending the Human Immunodeficiency Virus clinic (HIV at the University of Benin Teaching hospital, Benin City, Nigeria, within the period from February 2011- July 2011. Forty (18 males and 22 females HIV positive outpatients with CD4 counts >200 cells/µl who were ART-naive were recruited and used as controls. The sero-prevalence of crag in the patients and the control group was measured using the cryptococcal antigen latex agglutination system (CALAS (Meridian Bioscience, Europe and CD4 counts were measured using flow cytometry (Partec flow cytometer, Germany.Results: Of the 150 ART-naïve AIDS patients with CD4 counts £200 cells/µL; 19 (12.7% were positive for serum Cryptococcal antigen. ART-naïve AIDS patients with CD4 count ≤50 cells/µl had the highest prevalence of serum crag. Lower CD4 counts were significantly associated with positivity for serum crag (p<0.001. Age and sex had no significant effect on the sero-positivity for serum crag. One (2.5% of the controls was sero-positive for crag. Thus, serum crag was significantly associated with AIDS but not with HIV (p<0.001.Conclusion: This study uncovers a high prevalence of crag in ART- naïve AIDS patients in Benin City. The prevalence of crag was higher in ART-naïve AIDS patients with lower CD4 counts. There is an urgent need to

  5. Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals

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    Shilaih, Mohaned; Marzel, Alex; Braun, Dominique L.; Scherrer, Alexandra U.; Kovari, Helen; Young, Jim; Calmy, Alexandra; Darling, Katharine; Battegay, Manuel; Hoffmann, Matthias; Bernasconi, Enos; Thurnheer, Maria C.; Günthard, Huldrych F.; Kouyos, Roger D.

    2017-01-01

    Abstract After several years of steady decline, syphilis is reemerging globally as a public health hazard, especially among people living with human immunodeficiency virus (HIV). Syphilis resurgence is observed mainly in men who have sex with men (MSM), yet other transmission groups are affected too. In this manuscript, we study the factors associated with syphilis incidence in the Swiss HIV cohort study in the era of highly effective antiretrovirals. Using parametric interval censored models with fixed and time-varying covariates, we studied the immunological, behavioral, and treatment-related elements associated with syphilis incidence in 3 transmission groups: MSM, heterosexuals, and intravenous drug users. Syphilis incidence has been increasing annually since 2005, with up to 74 incident cases per 1000 person-years in 2013, with MSM being the population with the highest burden (92% of cases). While antiretroviral treatment (ART) in general did not affect syphilis incidence, nevirapine (NVP) was associated with a lower hazard of syphilis incidence (multivariable hazard ratio 0.5, 95% confidence interval 0.2–1.0). We observed that condomless sex and younger age were associated with higher syphilis incidence. Moreover, time-updated CD4, nadir CD4, and CD8 cell counts were not associated with syphilis incidence. Finally, testing frequency higher than the recommended once a year routine testing was associated with a 2-fold higher risk of acquiring syphilis. Condomless sex is the main driver of syphilis resurgence in the Swiss HIV Cohort study; ART and immune reconstitution provide no protection against syphilis. This entails targeted interventions and frequent screening of high-risk populations. There is no known effect of NVP on syphilis; therefore, further clinical, epidemiological, and microbiological investigation is necessary to validate our observation. PMID:28079818

  6. Antiretroviral therapy availability and HIV disclosure to spouse in Rakai, Uganda: a longitudinal population-based study

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    HABERLEN, Sabina A.; NAKIGOZI, Gertrude; GRAY, Ronald H.; BRAHMBHATT, Heena; SSEKASANVU, Joseph; SERWADDA, David; NALUGODA, Fred; KAGAAYI, Joseph; WAWER, Maria. J.

    2015-01-01

    Background A decade after the rollout of antiretroviral therapy (ART) in sub-Saharan Africa, the effects of this structural change on social aspects of HIV such as rates of HIV disclosure to partners remain largely unmeasured. We evaluated whether the introduction of ART was associated with disclosure of HIV diagnosis to spouses in Rakai, Uganda, using longitudinal, population-based data. Methods We identified individuals in marital/cohabitating unions who were newly diagnosed with HIV in Rakai Community Cohort Study (RCCS) surveys between 2000 and 2008, where antiretroviral therapy (ART) was introduced in mid-2004. Using discrete-time survival analysis, we assessed the hazard of self-reported HIV disclosure to spouse after diagnosis pre- and post-ART rollout, adjusting for individual and union characteristics. Disclosure in the ART period was further stratified by ART initiation. Results The analysis included 557 married adults, 264 of whom were diagnosed with HIV before ART was available (2000-2004) and 293 diagnosed after ART was introduced (2005-2008). The cumulative incidence of self-reported disclosure was 75.2% in the post-ART period, compared to 58.3% before ART availability (p<0.001, adjusted hazard 1.46 [95% CI 1.16, 1.83]). In the post-ART period, observed disclosure rates were 39% (72/184) among those not in HIV care, 65% (82/126) among those in pre-ART care, and 85% (64/75) among persons on ART (p<0.001). Conclusions Treatment availability and use, especially ART initiation, was associated with increased self-disclosure of HIV diagnosis to partners. ART access may facilitate the prevention of transmission to uninfected partners and linkage to treatment for infected couples. PMID:26009833

  7. Bounded agency in humanitarian settings: a qualitative study of adherence to antiretroviral therapy among refugees situated in Kenya and Malaysia.

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    Mendelsohn, Joshua B; Rhodes, Tim; Spiegel, Paul; Schilperoord, Marian; Burton, John Wagacha; Balasundaram, Susheela; Wong, Chunting; Ross, David A

    2014-11-01

    HIV-positive refugees confront a variety of challenges in accessing and adhering to antiretroviral therapy (ART) and attaining durable viral suppression; however, there is little understanding of what these challenges are, how they are navigated, or how they may differ across humanitarian settings. We sought to document and examine accounts of the threats, barriers and facilitators experienced in relation to HIV treatment and care and to conduct comparisons across settings. We conducted semi-structured interviews among a purposive sample of 14 refugees attending a public, urban HIV clinic in Kuala Lumpur, Malaysia (July-September 2010), and 12 refugees attending a camp-based HIV clinic in Kakuma, Kenya (February-March 2011). We used framework methods and between-case comparison to analyze and interpret the data, identifying social and environmental factors that influenced adherence. The multiple issues that threatened adherence to antiretroviral therapy or precipitated actual adherence lapses clustered into three themes: "migration", "insecurity", and "resilience". The migration theme included issues related to crossing borders and integrating into treatment systems upon arrival in a host country. Challenges related to crossing borders were reported in both settings, but threats pertaining to integration into, and navigation of, a new health system were exclusive to the Malaysian setting. The insecurity theme included food insecurity, which was most commonly reported in the Kenyan setting; health systems insecurity, reported in both settings; and emotional insecurity, which was most common in the Kenyan setting. Resilient processes were reported in both settings. We drew on the concept of "bounded agency" to argue that, despite evidence of personal and community resilience, these processes were sometimes insufficient for overcoming social and environmental barriers to adherence. In general, interventions might aim to bolster individuals' range of action with

  8. Miliary tuberculosis in human immunodeficiency virus infected patients not on antiretroviral therapy: Clinical profile and response to shortcourse chemotherapy

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    Swaminathan S

    2007-01-01

    Full Text Available Background: An increase in tuberculosis (TB incidence has been associated with human immunodeficiency virus (HIV. Aims: To describe the clinical characteristics and treatment outcome of patients with HIV and miliary TB treated with short-course intermittent chemotherapy in the absence of access to highly active antiretroviral therapy (HAART. Settings and Design: Prospective study of HIV infected adults referred to a TB clinic between July 1999 and July 2004. Materials and Methods: On diagnosis of miliary TB, patients were treated with a standard regimen of two months of isoniazid, rifampicin, ethambutol and pyrazinamide followed by four months of isoniazid and rifampicin (2EHRZ 3 /4RH 3 thrice weekly and followed up for 24 months. Patients were reviewed clinically every month and two sputa were collected. Chest radiographs and blood investigations were done at two months, end of treatment and every six months thereafter. Results: Of 498 patients with HIV and tuberculosis, 31 (6% were diagnosed as miliary tuberculosis. At diagnosis, sputum smear was positive for acid-fast bacilli (AFB in 14 patients (45% and Mycobacterium tuberculosis was isolated in 21 (68%. The mean CD4 cell count was 129 ± 125 cells/mm 3 . Twenty-five patients were declared cured at the end of treatment (81% while one (3% died and five (16% failed. The recurrence rate was 19.4/100 person-years and the median survival was 17 months (95% CI 14 to 20. None of the patients received antiretroviral therapy. Conclusions: Miliary TB tends to occur among HIV infected patients with severe immunosuppression. Though the initial response to short-course chemotherapy was encouraging, a high recurrence rate and mortality was observed indicating poor prognosis in HIV.

  9. Characteristics of HIV-1-specific CD8 T-cell responses and their role in loss of viremia in children chronically infected with HIV-1 undergoing highly active antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zheng; ZHAO Qing-xia; FU Jun-liang; YAO Jin-xia; HE Yun; JIN Lei; WANG Fu-sheng

    2006-01-01

    Background Few studies have examined the properties of human immunodeficiency virus type 1 (HIV-1) epitope-specific cytotoxic T lymphocyte (CTL) responses in children. To address this issue, we characterized epitope-specific CTL responses and analyzed the determinants that may affect CTL responses before and after highly active antiretroviral therapy (HAART) in children with HIV-1 infection.Methods A total of 22 HIV-1-infected children and 23 uninfected healthy children as control were enrolled in the study. Circulating CD4 T cells and HIV-1 RNA load in plasma were routinely measured. Peripheral HIV-1-specific CTL frequency and HIV-1 epitope-specific, interferon-γ (IFN-γ)-producing T lymphocytes were measured using tetramer staining and enzyme-linked immunospot (ELISPOT) assay, respectively.Circulating dendritic cell (DC) subsets were monitored with FACS analysis.Results More than 80% of the children with HIV-1 infection exhibited a positive HIV-1-epitope-specific CTL response at baseline, but HIV-specific CTLs and IFN-γ-producing lymphocytes decreased in patients who responded to HAART in comparison with non-responders and HAART-naive children. The duration of virus suppression resulted from HAART was inversely correlated with CTL frequency. While in HAART-naive children, HIV-1-specific CTL frequency was positively correlated with myeloid DC (mDC) frequency,although the cause and effect relationship between the DCs and CTLs remains unknown.Conclusions HIV-1-epitope-specific CTL responses are dependent on antigenic stimulation. The impaired DC subsets in blood might result in a defect in DC-mediated T cell responses. These findings may provide insight into understanding the factors and related mechanisms that influence the outcome of HIV-1 carriers to HAART or future antiviral therapies.

  10. Modelling the impact of antiretroviral use in resource-poor settings.

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    Rebecca F Baggaley

    2006-04-01

    Full Text Available BACKGROUND: The anticipated scale-up of antiretroviral therapy (ART in high-prevalence, resource-constrained settings requires operational research to guide policy on the design of treatment programmes. Mathematical models can explore the potential impacts of various treatment strategies, including timing of treatment initiation and provision of laboratory monitoring facilities, to complement evidence from pilot programmes. METHODS AND FINDINGS: A deterministic model of HIV transmission incorporating ART and stratifying infection progression into stages was constructed. The impact of ART was evaluated for various scenarios and treatment strategies, with different levels of coverage, patient eligibility, and other parameter values. These strategies included the provision of laboratory facilities that perform CD4 counts and viral load testing, and the timing of the stage of infection at which treatment is initiated. In our analysis, unlimited ART provision initiated at late-stage infection (AIDS increased prevalence of HIV infection. The effect of additionally treating pre-AIDS patients depended on the behaviour change of treated patients. Different coverage levels for ART do not affect benefits such as life-years gained per person-year of treatment and have minimal effect on infections averted when treating AIDS patients only. Scaling up treatment of pre-AIDS patients resulted in more infections being averted per person-year of treatment, but the absolute number of infections averted remained small. As coverage increased in the models, the emergence and risk of spread of drug resistance increased. Withdrawal of failing treatment (clinical resurgence of symptoms, immunologic (CD4 count decline, or virologic failure (viral rebound increased the number of infected individuals who could benefit from ART, but effectiveness per person is compromised. Only withdrawal at a very early stage of treatment failure, soon after viral rebound, would have a

  11. Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1–Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda

    Science.gov (United States)

    Baeten, Jared M.; Heffron, Renee; Kidoguchi, Lara; Mugo, Nelly R.; Katabira, Elly; Bukusi, Elizabeth A.; Asiimwe, Stephen; Haberer, Jessica E.; Ngure, Kenneth; Bulya, Nulu; Odoyo, Josephine; Hendrix, Craig; Marzinke, Mark A.; Ware, Norma C.; Wyatt, Monique A.; Morrison, Susan; Mujugira, Andrew; Donnell, Deborah; Celum, Connie

    2016-01-01

    Background Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings. Methods and Findings Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7–6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0–0.9, p 5% per year. PMID:27552090

  12. HIV DNA reservoir increases risk for cognitive disorders in cART-naive patients.

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    Victor G Valcour

    Full Text Available OBJECTIVES: Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART. Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14(+ enriched monocytes predicted cognitive impairment and brain injury. METHODS: We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14(+ enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF. RESULTS: The mean (SD age was 35 (6.9 years, CD4 T-lymphocyte count was 236 (139 and log10 plasma HIV RNA was 4.8 (0.73. Twenty-eight of 61 met HAND criteria. The log10 CD14(+ HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001. There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number. Plasma CD14(+ HIV DNA was associated with plasma and CSF neopterin (p = 0.023 and with MRS markers of neuronal injury (lower N-acetyl aspartate and glial dysfunction (higher myoinositol in multiple brain regions. INTERPRETATION: Reservoir burden of HIV DNA in monocyte-enriched (CD14(+ peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.

  13. Abacavir-reactive memory T cells are present in drug naive individuals.

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    Andrew Lucas

    Full Text Available Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population.To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling.Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells.We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection.

  14. Rates and factors associated with major modifications to first-line combination antiretroviral therapy: results from the Asia-Pacific region.

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    Stephen Wright

    Full Text Available BACKGROUND: In the Asia-Pacific region many countries have adopted the WHO's public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART in resource-rich and resource-limited countries in the region. METHODS: We selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD and the TREAT Asia HIV Observational Database (TAHOD. We dichotomised each country's per capita income into high/upper-middle (T-H and lower-middle/low (T-L. Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV or a substitution of two or more ARV agents from within the same ARV class. RESULTS: A total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI of treatment modification was 0.48 (0.44-0.52, 0.33 (0.30-0.36 and 0.21 (0.18-0.23 for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL, quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL, monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring. CONCLUSIONS: Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher

  15. Long-Term Durability of Tenofovir-Based Antiretroviral Therapy in Relation to the Co-Administration of Other Drug Classes in Routine Clinical Practice

    Science.gov (United States)

    Bonora, Stefano; Madeddu, Giordano; Maggiolo, Franco; Antinori, Andrea; Galli, Massimo; Di Perri, Giovanni; Viale, Pierluigi; d’Arminio Monforte, Antonella; Gori, Andrea

    2016-01-01

    Background In clinical trials, toxicity leading to tenofovir disoproxil fumarate (TDF) discontinuation is rare (3% by 2 years); however in clinical practice it seems to be higher, particularly when TDF is co-administered with ritonavir-boosted protease inhibitors (PI/r). Aims of this study were to assess the rate of TDF discontinuations in clinical practice and to identify factors associated with the risk of stopping TDF. Methods All antiretroviral treatment (ART)-naive patients initiating a TDF-based regimen were selected from the ICONA Foundation Study cohort. The primary outcome was TDF discontinuation regardless of the reason; secondary outcome measures were TDF discontinuation due to toxicity and selective TDF discontinuation (that is, TDF discontinuation or substitution, maintaining unchanged the remaining antiretroviral treatment). Results 3,618 ART-naïve patients were included: 54% started a PI/r-based and 46% a NNRTI-based based regimen. Two-hundred-seventy-seven patients discontinued TDF and reintroduced ART within 30 days without TDF. The probability of TDF discontinuation regardless of the reason was of 7.4% (95%CI:6.4–8.5) by 2 years and 14.1% (95%CI:12.2–16.1) by 5 years. The 5-year KM estimates in the PI/r vs. NNRTI group were 20.4% vs. 7.6%, respectively (log-rank p = 0.0001), for the outcome of stopping regardless of the reason, and 10.7% vs. 4.7% (p = 0.0001) for discontinuation due to toxicity. PI/r use and lower eGFR were associated with an increased risk of discontinuing TDF. Conclusion In our cohort, the frequency of TDF discontinuations was higher than that observed in clinical trials. Co-administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. Further studies are needed to clarify the mechanisms that might have led to this outcome. PMID:27716843

  16. Personalized ophthalmology.

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    Porter, L F; Black, G C M

    2014-07-01

    Ophthalmology has been an early adopter of personalized medicine. Drawing on genomic advances to improve molecular diagnosis, such as next-generation sequencing, and basic and translational research to develop novel therapies, application of genetic technologies in ophthalmology now heralds development of gene replacement therapies for some inherited monogenic eye diseases. It also promises to alter prediction, diagnosis and management of the complex disease age-related macular degeneration. Personalized ophthalmology is underpinned by an understanding of the molecular basis of eye disease. Two important areas of focus are required for adoption of personalized approaches: disease stratification and individualization. Disease stratification relies on phenotypic and genetic assessment leading to molecular diagnosis; individualization encompasses all aspects of patient management from optimized genetic counseling and conventional therapies to trials of novel DNA-based therapies. This review discusses the clinical implications of these twin strategies. Advantages and implications of genetic testing for patients with inherited eye diseases, choice of molecular diagnostic modality, drivers for adoption of personalized ophthalmology, service planning implications, ethical considerations and future challenges are considered. Indeed, whilst many difficulties remain, personalized ophthalmology truly has the potential to revolutionize the specialty.

  17. Personality disorder

    DEFF Research Database (Denmark)

    Tyrer, Peter; Mulder, Roger; Crawford, Mike

    2010-01-01

    Personality disorder is now being accepted as an important condition in mainstream psychiatry across the world. Although it often remains unrecognized in ordinary practice, research studies have shown it is common, creates considerable morbidity, is associated with high costs to services...... increasing evidence that some treatments, mainly psychological, are of value in this group of disorders. What is now needed is a new classification that is of greater value to clinicians, and the WPA Section on Personality Disorders is currently undertaking this task....... and to society, and interferes, usually negatively, with progress in the treatment of other mental disorders. We now have evidence that personality disorder, as currently classified, affects around 6% of the world population, and the differences between countries show no consistent variation. We are also getting...

  18. Effect of antiretroviral therapy on malaria incidence in HIV-infected Ugandan adults

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    Kasirye, Ronnie P.; Grosskurth, Heiner; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Baisley, Kathy

    2017-01-01

    Introduction: Using the data of a trial on cotrimoxazole (CTX) cessation, we investigated the effect of different antiretroviral therapy (ART) regimens on the incidence of clinical malaria. Methods: During the cotrimoxazole cessation trial (ISRCTN44723643), HIV-infected Ugandan adults with CD4+ at least 250 cells/μl were randomized to receive either CTX prophylaxis or placebo and were followed for a median of 2.5 years. Blood slides for malaria microscopy were examined at scheduled visits and at unscheduled visits when the participant felt unwell. CD4+ cell counts were done 6-monthly. Malaria was defined as fever with a positive blood slide. ART regimens were categorized as nucleoside reverse transcriptase inhibitor (NRTI) only, non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing or protease inhibitor containing. Malaria incidence was calculated using random effects Poisson regression to account for clustering of events. Results: Malaria incidence in the three ART regimen groups was 9.9 (3.6-27.4), 9.3 (8.3-10.4), and 3.5 (1.6-7.6) per 100 person-years, respectively. Incidence on protease inhibitors was lower than that on the other regimens with the results just reaching significance (adjusted rate ratio 0.4, 95% confidence interval = 0.2–1.0, comparing with NNRTI regimens). Stratification by CTX/placebo use gave similar results, without evidence of an interaction between the effects of CTX/placebo use and ART regimen. There was no evidence of an interaction between ART regimen and CD4+ cell count. Conclusion: There was some evidence that protease inhibitor-containing ART regimens may be associated with a lower clinical malaria incidence compared with other regimens. This effect was not modified by CTX use or CD4+ cell count. The antimalarial properties of protease inhibitors may have clinical and public health importance. PMID:28121670

  19. HIV stigma and associated factors among antiretroviral treatment clients in Jimma town, Southwest Ethiopia

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    Nikus Fido N

    2016-11-01

    Full Text Available Neno Nikus Fido, Mamusha Aman, Zewdie Brihnu Department of Health Education and Behavioral Sciences, Jimma University, Jimma, Ethiopia Background: HIV stigma has an important role in the spread of the AIDS epidemic. It profoundly affects the lives of individuals living with HIV/AIDS. Fear of being identified as having HIV may discourage a person from getting tested, accessing medical services, and obtaining medications. Thus, this study was aimed at assessing HIV-related stigma and associated factors among antiretroviral treatment (ART clients in Jimma town, Oromia region, Southwest Ethiopia. Methods: A facility-based cross-sectional study was conducted from March 11 to April 26, 2015, in ART clinics in Jimma town. Consecutively identified sample was obtained from ART clients who voluntarily participated in the survey after signing written consent. A structured interviewer-administered questionnaire was used to collect the data. Multiple linear regressions were conducted to assess the factors associated with various stigma domains. Results: Out of 349 clients requested, 318 (91.1% respondents voluntarily participated in the study; among them, 204 (64.2% respondents were females and the mean age of the respondents was 32.9 years. The mean score (and possible range of experienced HIV stigma was 41.5±12.6 (20.0–86.7, internalized stigma was 50.5±16.4 (20–96.5, and perceived stigma was 56.2±19.2 (20–100. Conclusion: The study revealed that duration of ART use and provider-initiated and forced HIV testing were significantly associated with the three HIV stigma domains. Despite the lower experienced HIV stigma, there were higher internalized and perceived stigmas. Therefore, HIV counseling services should be strengthened for new ART beginners, including pretest counseling. Keywords: HIV/AIDS, Jimma, stigma, ART clients, PLWHA

  20. Renal Function in Chinese HIV-Positive Individuals following Initiation of Antiretroviral Therapy.

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    Yan Zhao

    Full Text Available To identify the prevalence and predictors of abnormal renal function among HIV-positive Chinese patients prior to antiretroviral therapy (ART initiation and to evaluate subsequent changes in renal function after ART exposure.We conducted a nationwide cohort study of subjects who enrolled in the national Chinese ART program from January 1, 2012 to December 31, 2012. We estimated the glomerular filtration rate (eGFR of subjects prior to and after initiating ART. Risk factors for abnormal renal function, as defined by eGFR 6.1 mmol/L (AOR = 1.46, 95% CI: 1.25-1.72, and hepatitis C co-infection (AOR = 1.36, 95% CI: 1.06-1.73. Among subjects with baseline eGFR >90 ml/min/1.73m2, the incidence of the eGFR falling to <60 ml/min/1.73m2 was 0.92/100 person-years after a median of 15.0 months of ART. Being on a tenofovir with lopinavir/ritonavir regimen (Adjusted hazard ratio [AHR] = 3.02, 95% CI: 1.96-4.66 and having an unsuppressed viral load (AHR = 2.70, 95% CI: 1.80-4.03 were independent predictors for eGFR <60 ml/min/1.73m2 after ART initiation as well as older age, female, and hemoglobin <120 g/L.A high proportion of HIV-positive subjects in China presented with abnormal renal function prior to ART initiation. But the incidence of the eGFR decrease after ART was low. Patient renal function should be regularly monitored by eGFR before initiating and during ART.

  1. Incident pregnancy and time to death or AIDS among HIV-positive women receiving antiretroviral therapy.

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    Daniel Westreich

    Full Text Available BACKGROUND: Little is known about the impact of pregnancy on response to highly active antiretroviral therapy (HAART in sub-Saharan Africa. We examined the effect of incident pregnancy after HAART initiation on clinical response to HAART. METHODS: We evaluated a prospective clinical cohort of adult women initiating HAART in Johannesburg, South Africa between 1 April 2004 and 31 March 2011, and followed up until an event, transfer, drop-out, or administrative end of follow-up on 30 September 2011. Women over age 45 and women who were pregnant at HAART initiation were excluded from the study. Main exposure was having experienced pregnancy after HAART initiation; main outcome was death and (separately death or new AIDS event. We calculated adjusted hazard ratios (HRs and 95% confidence limits (CL using marginal structural Cox proportional hazards models. RESULTS: The study included 7,534 women, and 20,813 person-years of follow-up; 918 women had at least one recognized pregnancy during follow-up. For death alone, the weighted (adjusted HR was 0.84 (95% CL 0.44, 1.60. Sensitivity analyses confirmed main results, and results were similar for analysis of death or new AIDS event. Incident pregnancy was associated with a substantially reduced hazard of drop-out (HR = 0.62, 95% CL 0.51, 0.75. CONCLUSIONS: Recognized incident pregnancy after HAART initiation was not associated with increases in hazard of clinical events, but was associated with a decreased hazard of drop-out. High rates of pregnancy after initiation of HAART may point to a need to better integrate family planning services into clinical care for HIV-infected women.

  2. Who is utilizing anti-retroviral therapy in Ghana: An analysis of ART service utilization

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    Dako-Gyeke Phyllis

    2012-10-01

    Full Text Available Abstract Introduction The global scale-up of antiretroviral therapy (ART for HIV patients has led to concerns regarding inequities in utilization of ART services in resource-limited contexts. In this paper, we describe regional and sex differentials in the distribution of ART among adult HIV patients in Ghana. We highlight the need for interventions to address the gender-based and geographic inequities related to the utilization of ART services in Ghana. Methods We reviewed National AIDS/STIs Control Program’s ART service provision records from January 2003 through December 2010, extracting data on adults aged 15+ who initiated ART in Ghana over a period of eight years. Data on the number of patients on treatment, year of enrollment, sex, and region were obtained and compared. Results The number of HIV patients receiving ART in Ghana increased more than 200-fold from 197 in 2003, to over 45,000 in 2010. However, for each of six continuous years (2005-2010 males comprised approximately one-third of adults newly enrolled on ART. As ART coverage has expanded in Ghana, the proportion of males receiving ART declined from 41.7% in 2004 to 30.1% in 2008 and to 27.6% in 2010. Also, there is disproportionate regional ART utilization across the country. Some regions report ART enrollment lower than their percent share of number of HIV infected persons in the country. Conclusions Attention to the comparatively fewer males initiating ART, as well as disproportionate regional ART utilization is urgently needed. All forms of gender-based inequities in relation to HIV care must be addressed in order for Ghana to realize successful outcomes at the population level. Policy makers in Ghana and elsewhere need to understand how gender-based health inequities in relation to HIV care affect both men and women and begin to design appropriate interventions.

  3. Retention in an antiretroviral therapy programme during an era of decreasing drug cost in Limbe, Cameroon

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    Mosoko Jembia J

    2011-06-01

    Full Text Available Abstract Background In 2002, Cameroon initiated scale up of antiretroviral therapy (ART; on 1 October 2004, a substantial reduction in ART cost occurred. We assessed the impact of this event and other factors on enrolment and retention in care among HIV-infected patients initiating ART from February 2002 to December 2005 at the single ART clinic serving the Southwest Region in Limbe, Cameroon. Methods We retrospectively analyzed clinical and pharmacy payment records of HIV-infected patients initiating ART according to national guidelines. We compared two cohorts of patients, enrolled before and after 1 October 2004, to determine if price reduction was associated with enhanced enrolment. We assessed factors associated with retention and survival by Cox proportional hazards models. Retention in care implied patients who had contact with the healthcare system as of 31 December 2005 (including those who were transferred to continue care in other ART centres, although these patients may have interrupted therapy at some time. A patient who was not retained in care may have dropped out (lost to follow up or died. Results Mean enrolment rates for 2920 patients who initiated ART before and after the price reduction were 46.5 and 95.5 persons/month, respectively (p Conclusions Reducing the cost of ART increased enrolment of clients in the programme, but did not change retention in care. In a system where most clients pay for ART, an accessible clinic location may be more important than the cost of medication for retention in care. Decentralizing ART clinics might improve retention and survival among patients on ART.

  4. Patient attrition from the HIV antiretroviral therapy program at two hospitals in Haiti

    Science.gov (United States)

    Puttkammer, Nancy H.; Zeliadt, Steven B.; Baseman, Janet G.; Destiné, Rodney; Domerçant, Jean Wysler; Coq, Nancy Rachel Labbé; Raphael, Nernst Atwood; Sherr, Kenneth; Tegger, Mary; Yuhas, Krista; Barnhart, Scott

    2016-01-01

    Objective To identify factors associated with antiretroviral therapy (ART) attrition among patients initiating therapy in 2005–2011 at two large, public-sector department-level hospitals, and to inform interventions to improve ART retention. Methods This retrospective cohort study used data from the iSanté electronic medical record (EMR) system. The study characterized ART attrition levels and explored the patient demographic, clinical, temporal, and service utilization factors associated with ART attrition, using time-to-event analysis methods. Results Among the 2 023 patients in the study, ART attrition on average was 17.0 per 100 person-years (95% confidence interval (CI): 15.8–18.3). In adjusted analyses, risk of ART attrition was up to 89% higher for patients living in distant communes compared to patients living in the same commune as the hospital (hazard ratio: 1.89, 95%CI: 1.54–2.33; P < 0.001). Hospital site, earlier year of ART start, spending less time enrolled in HIV care prior to ART initiation, receiving a non-standard ART regimen, lacking counseling prior to ART initiation, and having a higher body mass index were also associated with attrition risk. Conclusions The findings suggest quality improvement interventions at the two hospitals, including: enhanced retention support and transportation subsidies for patients accessing care from remote areas; counseling for all patients prior to ART initiation; timely outreach to patients who miss ART pick-ups; “bridging services” for patients transferring care to alternative facilities; routine screening for anticipated interruptions in future ART pick-ups; and medical case review for patients placed on non-standard ART regimens. The findings are also relevant for policymaking on decentralization of ART services in Haiti. PMID:25563149

  5. Hepatotoxicity of antiretrovirals in patients with human immunodeficiency virus and viral hepatitis coinfections

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    P Parenti

    2012-11-01

    Full Text Available Background: Antiretroviral drugs used to treat HIV may cause hepatotoxicity. The high prevalence of persons with chronic hepatitis B or C coinfected, raised aminotransferases have many causes and neither specific markers is a indicator of liver injury, difficulties in interpreting the hepatotoxicity. Objective: We evaluated hepatotoxicity in HIV/HCV- and/or HBV-coinfected patients, risk factors and severity. Methods: Prospective study of HIV-1 patients with start HAART in Hospital Provincial del Centenario from Rosario, Argentina. Patients were classified into two groups, HCV and/or HBV coinfected vs. no coinfected. The major endpoint was hepatotoxicity defined as Benichou's Score within the first 6 months. This score is among the few validated, but little used in clinical practice. Secondary endpoints were risk factors and severity of hepatotoxicity. Results: 140 patients were included, 39% coinfected and 61% no coinfected. Females were similar in both groups; 21% and 27% respectively. The hepatotoxicity within the first 6 month was 44.3%, 75% in coinfected patients and 25% in no-coinfected. RR 3.97 (95% confidence interval 2.34–6.75, p<0.0001. The hepatotoxicity was associated with the use of illicit drugs and alcohol, symptoms, high level aminotransferases previous to HAART and NNRTI+PI. 3% of hepatotoxicity was severe. Conclusions: 44% of HIV patients experienced hepatotoxicity, 75% in coinfected vs 25% in no coinfected. The relative risk of hepatoxocity was almost 4 times higher among in chronic hepatitis-coinfected patients, compared with those with HIV non-coinfected. In multivariate analysis, the risk factors were illicit drugs, alcohol, symptoms, high level aminotransferases and NRTI+PI. Only 3% of hepatotoxicity was severe. The Benichou's Score is better than level of aminotransferase for evaluated hepatotoxicity, so it would be recommended for use in clinical practice.

  6. Evaluating preferences for profiles of glucagon-like peptide-1 receptor agonists among injection-naive type 2 diabetes patients in Japan

    Science.gov (United States)

    Gelhorn, Heather L; Bacci, Elizabeth D; Poon, Jiat Ling; Boye, Kristina S; Suzuki, Shuichi; Babineaux, Steven M

    2016-01-01

    Objective The objective of this study was to use a discrete choice experiment (DCE) to estimate patients’ preferences for the treatment features, safety, and efficacy of two specific glucagon-like peptide-1 receptor agonists, dulaglutide and liraglutide, among patients with type 2 diabetes mellitus (T2DM) in Japan. Methods In Japan, patients with self-reported T2DM and naive to treatment with self-injectable medications were administered a DCE through an in-person interview. The DCE examined the following six attributes of T2DM treatment, each described by two levels: “dosing frequency”, “hemoglobin A1c change”, “weight change”, “type of delivery system”, “frequency of nausea”, and “frequency of hypoglycemia”. Part-worth utilities were estimated using logit models and were used to calculate the relative importance (RI) of each attribute. A chi-square test was used to determine the differences in preferences for the dulaglutide versus liraglutide profiles. Results The final evaluable sample consisted of 182 participants (mean age: 58.9 [standard deviation =10.0] years; 64.3% male; mean body mass index: 26.1 [standard deviation =5.0] kg/m2). The RI values for the attributes in rank order were dosing frequency (44.1%), type of delivery system (26.3%), frequency of nausea (15.1%), frequency of hypoglycemia (7.4%), weight change (6.2%), and hemoglobin A1c change (1.0%). Significantly more participants preferred the dulaglutide profile (94.5%) compared to the liraglutide profile (5.5%; P70% of the RI. These findings are similar to those of a previous UK study, providing information about patients’ preferences that may be informative for patient–clinician treatment discussions. PMID:27524889

  7. Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy

    DEFF Research Database (Denmark)

    Filteau, Suzanne; PrayGod, George; Kasonka, Lackson;

    2015-01-01

    BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study...... was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART...... in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased...

  8. Duration of anti-tuberculosis therapy and timing of antiretroviral therapy initiation: association with mortality in HIV-related tuberculosis.

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    Claudia P Cortes

    Full Text Available BACKGROUND: Antiretroviral therapy (ART decreases mortality risk in HIV-infected tuberculosis patients, but the effect of the duration of anti-tuberculosis therapy and timing of anti-tuberculosis therapy initiation in relation to ART initiation on mortality, is unclear. METHODS: We conducted a retrospective observational multi-center cohort study among HIV-infected persons concomitantly treated with Rifamycin-based anti-tuberculosis therapy and ART in Latin America. The study population included persons for whom 6 months of anti-tuberculosis therapy is recommended. RESULTS: Of 253 patients who met inclusion criteria, median CD4+ lymphocyte count at ART initiation was 64 cells/mm(3, 171 (68% received >180 days of anti-tuberculosis therapy, 168 (66% initiated anti-tuberculosis therapy before ART, and 43 (17% died. In a multivariate Cox proportional hazards model that adjusted for CD4+ lymphocytes and HIV-1 RNA, tuberculosis diagnosed after ART initiation was associated with an increased risk of death compared to tuberculosis diagnosis before ART initiation (HR 2.40; 95% CI 1.15, 5.02; P = 0.02. In a separate model among patients surviving >6 months after tuberculosis diagnosis, after adjusting for CD4+ lymphocytes, HIV-1 RNA, and timing of ART initiation relative to tuberculosis diagnosis, receipt of >6 months of anti-tuberculosis therapy was associated with a decreased risk of death (HR 0.23; 95% CI 0.08, 0.66; P=0.007. CONCLUSIONS: The increased risk of death among persons diagnosed with tuberculosis after ART initiation highlights the importance of screening for tuberculosis before ART initiation. The decreased risk of death among persons receiving > 6 months of anti-tuberculosis therapy suggests that current anti-tuberculosis treatment duration guidelines should be re-evaluated.

  9. Rates of inappropriate antiretroviral prescription among injection drug users

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    Bonner Simon

    2007-01-01

    Full Text Available Abstract Background Although the survival benefits of antiretroviral therapy (ART for the treatment of HIV infection are well established, the clinical management of HIV disease continues to present major challenges. There are particular concerns regarding access to appropriate HIV treatment among HIV-infected injection drug users (IDU. Methods In a prospective cohort study of HIV-infected IDU in Vancouver, Canada, we examined initial ART regimens vis-à-vis the provincial government's therapeutic guidelines at the time ART was initiated. Briefly, there have been four sets of guidelines: Era 1 (1992 to November 1995; double-drug (dual NRTIs ART for patients with a CD4 cell count of 350 or less; Era 2 (December 1995 to May 1996; double-drug therapy for patients with a CD4+ cell count of 500 or less; Era 3 (June 1996 to June 1997; triple-drug therapy (dual NRTIs with a PI or NNRTI for patients who had a plasma viral load of > 100,000 HIV-1 RNA copies/mL; dual therapy with two NRTIs for those with a plasma viral load of 5,000 to 100,000 HIV-1 RNA copies/mL; Era 4 (since July 1997; universal use of triple drug therapy as first-line treatment. Results Between May 1996 and May 2003, 431 HIV-infected individuals were enrolled into the cohort. By May 31, 2003, 291 (67.5% individuals had initiated ART. We noted instances of inappropriate antiretroviral prescription in each guideline era, with 9 (53% in Era 1, 3 (12% in Era 2, 22 (28% in Era 3, and 23 (15% in Era 4. Of the 57 subjects who received an inappropriate ART regimen initially, 14 never received the appropriate therapy; among the remaining 43, the median time to the initiation of a guideline-appropriate ART regimen was 12 months (inter-quartile range 5 – 20. Conclusion The present study identified measurable rates of guideline-inappropriate ART prescription for patients who were injection drug users. Rates were highest in the era of dual therapy, although high rates persisted into the triple

  10. ARABIC PART OF SPEECH TAGGING USING K-NEAREST NEIGHBOUR AND NAIVE BAYES CLASSIFIERS COMBINATION

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    Rund Mahafdah

    2014-01-01

    Full Text Available Part Of Speech (POS tagging forms the important preprocessing step in many of the natural language processing applications such as text summarization, question answering and information retrieval system. It is the process of classifying every word in a given context to its appropriate part of speech. Different POS tagging techniques in the literature have been developed and experimented. Currently, it is well known that some POS tagging models are not performing well on the Quranic Arabic due to the complexity of the Quranic Arabic text. This complexity presents several challenges for POS tagging such as high ambiguity, data sparseness and large existence of unknown words. With this in mind, the main problem here is to find out how existing and efficient methods perform in Arabic and how can Quranic corpus be utilized to produce an efficient framework for Arabic POS tagging. We propose a classifiers combination experimental framework for Arabic POS tagger, by selecting two best diverse probabilistic classifiers used in numerous works in non-Arabic language; namely K-Nearest Neighbour (KNN and Naive Bayes (NB. The Majority voting is used here as the combination strategy to exploit classifiers advantages. In addition, an in-depth study has been conducted on a large list of features for exploiting effective features and investigating their role in enhancing the performance of POS taggers for the Quranic Arabic. Hence, this study aims to efficiently integrate different feature sets and tagging algorithms to synthesize more accurate POS tagging procedure. The data used in this study is the Arabic Quranic Corpus, an annotated linguistic resource consisting of 77,430 words with Arabic grammar, syntax and morphology for each word in the Holy Quran. The highest accuracy in the results achieved is 98.32%, which can be a significant enhancement for the state-of-the-art for Arabic Quranic text. The most effective features that yield this accuracy are a

  11. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

    Science.gov (United States)

    Westhovens, R; Robles, M; Ximenes, A C; Nayiager, S; Wollenhaupt, J; Durez, P; Gomez-Reino, J; Grassi, W; Haraoui, B; Shergy, W; Park, S-H; Genant, H; Peterfy, C; Becker, J-C; Covucci, A; Helfrick, R; Bathon, J

    2009-01-01

    Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile. PMID:19124524

  12. Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects.

    Science.gov (United States)

    Guy, Bruno; Nougarede, Nolwenn; Begue, Sarah; Sanchez, Violette; Souag, Nadia; Carre, Murielle; Chambonneau, Laurent; Morrisson, Dennis N; Shaw, David; Qiao, Ming; Dumas, Rafaele; Lang, Jean; Forrat, Remi

    2008-10-23

    Three independent, phase 1 clinical trials were conducted in Australia and in USA to assess the safety and immunogenicity of sanofi pasteur dengue vaccine candidates. In this context, Dengue 1-4 and Yellow Fever 17D-204 (YF 17D)-specific CD4 and CD8 cellular responses induced by tetravalent chimeric dengue vaccines (CYD) were analyzed in flavivirus-naive or flavivirus-immune patients. Tetravalent CYD vaccine did not trigger detectable changes in serum pro-inflammatory cytokines, whatever the vaccinees immune status, while inducing significant YF 17D NS3-specific CD8 responses and dengue serotype-specific T helper responses. These responses were dominated by serotype 4 in naive individuals, but a booster vaccination (dose #2) performed 4 months following dose #1 broadened serotype-specific responses. A similar, broader response was seen after primary tetravalent immunization in subjects with pre-existing dengue 1 or 2 immunity caused by prior monovalent live-attenuated dengue vaccination. In all three trials, the profile of induced response was similar, whatever the subjects' immune status, i.e. an absence of Th2 response, and an IFN-gamma/TNF-alpha ratio dominated by IFN-gamma, for both CD4 and CD8 responses. Our results also showed an absence of cross-reactivity between YF 17D or Dengue NS3-specific CD8 responses, and allowed the identification of 3 new CD8 epitopes in the YF 17D NS3 antigen. These data are consistent with the previously demonstrated excellent safety of these dengue vaccines in flavivirus-naive and primed individuals.

  13. Endoscopic findings can predict the efficacy of leukocytapheresis for steroid-naive patients with moderately active ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Yasushi Umehara; Masatoshi Kudo; Masanori Kawasaki

    2008-01-01

    AIM:To investigate the therapeutic usefulness of leukocytapheresis (LCAP;Cellsoba) in steroid-naive patients with moderately active ulcerative colitis (UC).METHODS:Eighteen steroid-naive patients with moderately active UC received one LCAP session every week for five consecutive weeks.RESULTS:The remission rate 8 weeks after the last LCAP session was 61.1% (11/18).All three patients with deep ulcers showed worsening after LCAP.For the remaining 15 patients,who had erosions or geographic ulcers,the average clinical activity index (CAI) score dropped significantly from 9.4 to 3.8eight weeks after the last LCAP session (t=4.89,P=0.001).The average C-reactive protein (CRP) levels before and after LCAP were 1.2 mg/dL and 1.0 mg/dL,respectively.Of the patients with erosions,geographic ulcers,and deep ulcers,100% (9/9),33.3% (2/6),and 0% (0/3) were in remission 8 weeks after the last LCAP session,respectively (x2=7.65,P < 0.005).Fortyeight weeks after the last LCAP session,the remission rates for patients with erosions and geographic ulcers were 44.4% (4/9) and 16.7% (1/6),respectively.Only one patient suffered a mild adverse event after LCAP (nausea).CONCLUSION:LCAP is a useful and safe therapy for steroid-naive UC patients with moderate disease activity.Moreover,the efficacy of the treatment can be predicted on the basis of endoscopic findings.

  14. Personality disorders

    NARCIS (Netherlands)

    van den Bosch, L.M.C.; Verheul, R.; Verster, J.C.; Brady, K.; Galanter, M.; Conrod, P.

    2012-01-01

    Subject of this chapter is the often found combination of personality disorders and ­substance abuse disorders. The serious nature of this comorbidity is shown through the discussion of prevalence and epidemiological data. Literature shows that the comorbidity, hampering the diagnostic process, is s

  15. Personalized ventilation

    DEFF Research Database (Denmark)

    Melikov, Arsen Krikor

    2004-01-01

    existing knowledge on performance of personalized ventilation (PV) and on human response to it. The airflow interaction in the vicinity of the human body is analyzed and its impact on thermal comfort and inhaled air quality is discussed together with control strategies and the application of PV in practice...

  16. Personalized nanomedicine

    NARCIS (Netherlands)

    Lammers, T.G.G.M.; Rizzo, L.Y.; Storm, G.; Kiessling, F.

    2012-01-01

    Abstract Personalized medicine aims to individualize chemotherapeutic interventions on the basis of ex vivo and in vivo information on patient- and disease-specific characteristics. By noninvasively visualizing how well image-guided nanomedicines-that is, submicrometer-sized drug delivery systems c

  17. Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy.

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    Boaz Avidor

    Full Text Available BACKGROUND: HIV subtypes A and CRF01_AE (A/AE became prevalent in Israel, first through immigration of infected people, mostly intravenous-drug users (IVDU, from Former Soviet-Union (FSU countries and then also by local spreading. We retrospectively studied virus-transmission patterns of these subtypes in comparison to the longer-established subtype B, evaluating in particular risk-group related differences. We also examined to what extent distinct drug-resistance patterns in subtypes A/AE versus B reflected differences in patient behavior and drug-treatment history. METHODS: Reverse-transcriptase (RT and protease sequences were retrospectively analyzed along with clinical and epidemiological data. MEGA, ClusalX, and Beast programs were used in a phylogenetic analysis to identify transmission networks. RESULTS: 318 drug-naive individuals with A/AE or patients failing combination antiretroviral therapy (cART were identified. 61% were IVDU. Compared to infected homosexuals, IVDU transmitted HIV infrequently and, typically, only to a single partner. 6.8% of drug-naive patients had drug resistance. Treatment-failing, regimen-stratified subtype-A/AE- and B-patients differed from each other significantly in the frequencies of the major resistance-conferring mutations T215FY, K219QE and several secondary mutations. Notably, failing boosted protease-inhibitors (PI treatment was not significantly associated with protease or RT mutations in either subtype. CONCLUSIONS: While sizable transmission networks occur in infected homosexuals, continued HIV transmission among IVDU in Israel is largely sporadic and the rate is relatively modest, as is that of drug-resistance transmission. Deviation of drug-naive A/AE sequences from subtype-B consensus sequence, documented here, may subtly affect drug-resistance pathways. Conspicuous differences in overall drug-resistance that are manifest before regimen stratification can be largely explained in terms of treatment

  18. CD4 Variability in Malawi: Implications for Use of a CD4 Threshold of 500 Cells/mm3 Versus Universal Eligibility for Antiretroviral Therapy

    Science.gov (United States)

    Schooley, Alan L.; Kamudumuli, Pocha Samuel; Vangala, Sitaram; Tseng, Chi-hong; Soko, Chifundo; Parent, Julie; Phiri, Khumbo; Jahn, Andreas; Namarika, Dan; Hoffman, Risa M.

    2016-01-01

    Background. Given the uncertainty about the ability of a single CD4 count to accurately classify a patient as antiretroviral therapy (ART) eligible, we sought to understand the extent to which CD4 variability results in misclassification at a CD4 threshold of 500 cells/mm3. Methods. We performed a prospective study of CD4 variability in Malawian human immunodeficiency virus-infected, ART-naive, World Health Organization (WHO) stage 1 or 2, nonpregnant adults. CD4 counts were performed daily for 8 days. We fit a Bayesian linear mixed-effects model of log-transformed CD4 cell counts to the data. We used Monte Carlo approximations to estimate misclassification rates for different observed values of CD4. The misclassification rate was calculated based on the conditional probability of true CD4 given the geometric mean of observed CD4 measurements. Results. Fifty patients were enrolled from 2 sites. The median age was 33.5 years (interquartile range, 27.5–40.0) and 34 (68%) were female. Misclassification rates were <1% when the observed CD4 counts were ≤250 or ≥750 cells/mm3. Rates of misclassification were high at observed CD4 counts between 350 and 650 cells/mm3, particularly when a single measurement was used (up to 46.7%). Conclusions. Our data show that ART eligibility based on a single CD4 count results in highest risk of misclassification when observed CD4 counts are in the range of 350–650 cells/mm3. Given the benefits of early ART, countries should weigh the costs and complexity of CD4 testing using a 500 cell/mm3 threshold against the cost savings and public health benefits of universal eligibility. PMID:27704028

  19. Longitudinal changes of peripheral blood DC subsets and regulatory T cells in Chinese chronic HIV-1-infected patients during antiretroviral therapy.

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    Mei Zhang

    Full Text Available It has been emphasized that chronic generalized immune dysfunction is the leading event in the pathogenesis of HIV infection, in which the contribution of dendritic cells (DCs and regulatory T cells (Tregs should not be underestimated. In current study, we assessed the longitudinal changes of peripheral blood DC subsets and Tregs in chronically asymptomatic treatment-naive HIV-1-infected patients during 60 weeks of antiretroviral therapy (ART, and compared with those in healthy controls and long term non-progressors (LTNPs. Blood samples were collected at week 0, 4, 12, 24, 48 and 60 of treatment to measure the counts of DC subsets and Tregs by flow cytometry and IFN-a plasma levels by ELISA. The counts of myeloid dendritic cells (mDCs increased during ART, reaching similar levels to healthy controls at week 60 post ART but still lower than those of LTNPs. In HIV-1-infected patients, the mDCs counts were directly correlated with CD4 counts during ART. Changes in mDCs at week 8 were positively correlated with the changes in CD4 counts at week 60 post ART. However, the counts and function of plasmacytoid dendritic cells (pDCs remained relatively stable during ART, and similar to those in healthy controls and LTNPs. The percentage of Tregs increased before ART and normalized after ART. Importantly, we found pDCs counts were associated with percentage of Tregs during ART, which may help in understanding of the role of these cells in HIV infection.

  20. A prospective, cross-sectional study of anaemia and peripheral iron status in antiretroviral naïve, HIV-1 infected children in Cape Town, South Africa

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    Hussey Gregory D

    2002-02-01

    Full Text Available Abstract Background Anaemia is a common manifestation of paediatric HIV infection. Although there are many causes, anaemia of chronic diseases is the most frequent type. In poor countries iron deficiency is widespread. It is probable that many HIV-infected children in these countries are also iron deficient. This study describes the relationship between paediatric HIV infection and anaemia, and documents the peripheral iron status of antiretroviral naive, HIV-infected children. Methods Sixty children were evaluated prospectively. Investigations included CD4+ count, haemoglobin concentration (Hb, red blood cell (RBC morphology, and iron studies. Results Anaemia was present in 73% of children. Compared to mild HIV infection, median Hb was lower in children with moderate clinical infection (104 g/L v 112 g/L, p = 0.04 and severe clinical infection (96 g/L v 112 g/L, p = 0.006, and more children with severe infection were anaemic (92% v 58%, 0.04. There was a significant relationship between immunological status and Hb. 68% had abnormal RBC morphology. Significantly more children with moderate and severe disease, and severe immunosuppression had abnormal RBC morphology. 52% were iron-depleted, 20% had iron-deficient erythropoiesis and 18% iron deficiency anaemia (IDA. 16% (7/44 of anaemic children had microcytosis and hypochromia. Median soluble transferrin receptor concentration was significantly higher in those with microcytic hypochromic anaemia (42.0 nmol/L v 30.0 nmol/L, p = 0.008. Conclusions Both the proportion of anaemic children and the median Hb were associated with disease status. Iron depletion and IDA are major problems in HIV-infected children in South Africa.

  1. Prevalence and evolution of low frequency HIV drug resistance mutations detected by ultra deep sequencing in patients experiencing first line antiretroviral therapy failure.

    Directory of Open Access Journals (Sweden)

    Marie-Anne Vandenhende

    Full Text Available OBJECTIVES: Clinical relevance of low-frequency HIV-1 variants carrying drug resistance associated mutations (DRMs is still unclear. We aimed to study the prevalence of low-frequency DRMs, detected by Ultra-Deep Sequencing (UDS before antiretroviral therapy (ART and at virological failure (VF, in HIV-1 infected patients experiencing VF on first-line ART. METHODS: Twenty-nine ART-naive patients followed up in the ANRS-CO3 Aquitaine Cohort, having initiated ART between 2000 and 2009 and experiencing VF (2 plasma viral loads (VL >500 copies/ml or one VL >1000 copies/ml were included. Reverse transcriptase and protease DRMs were identified using Sanger sequencing (SS and UDS at baseline (before ART initiation and VF. RESULTS: Additional low-frequency variants with PI-, NNRTI- and NRTI-DRMs were found by UDS at baseline and VF, significantly increasing the number of detected DRMs by 1.35 fold (p<0.0001 compared to SS. These low-frequency DRMs modified ARV susceptibility predictions to the prescribed treatment for 1 patient at baseline, in whom low-frequency DRM was found at high frequency at VF, and 6 patients at VF. DRMs found at VF were rarely detected as low-frequency DRMs prior to treatment. The rare low-frequency NNRTI- and NRTI-DRMs detected at baseline that correlated with the prescribed treatment were most often found at high-frequency at VF. CONCLUSION: Low frequency DRMs detected before ART initiation and at VF in patients experiencing VF on first-line ART can increase the overall burden of resistance to PI, NRTI and NNRTI.

  2. An information system to manage the rollout of the antiretroviral treatment programme in the Free State

    Directory of Open Access Journals (Sweden)

    J.E. Kotzé

    2010-09-01

    Full Text Available The Acquired Immune Deficiency Syndrome epidemic, caused by the Human Immunodeficiency Virus, is a global crisis which threatens development gains, economies, and societies. Within sub-Saharan Africa, where the epidemic began the earliest and the HIV prevalence is the highest, African countries have death rates not seen before. In South Africa the epidemic has a devastating impact which creates profound suffering on individuals and their families, and the impact on the socio-economic level is of great concern. The eradication of HIV/AIDS represents one of humanity’s greatest challenges, which requires co-operation and comprehensive collaboration between many different role players. In this endeavour clinical information plays a major role. To combat the effect of the disease, the Free State Department of Health started with the provisioning of antiretroviral therapy in the public health sector. The objective of this paper was to address the challenges they faced in order to develop and implement an information system to manage the rollout of antiretroviral treatment effectively. They started with a paper-based system to collect vital information. It was followed by a palm computer project that was initiated to electronically capture the data collected by the paper-based system. This system was then replaced by a comprehensive Hospital and Clinic Information System which was acquired and customised for the antiretroviral data collection process. Research partners developed a standalone antiretroviral data warehouse for collecting information associated with the monitoring and evaluation of the Free State antiretroviral and HIV/ AIDS treatment programme. The data warehouse successfully produced several management information reports to the antiretroviral management team. A need was identified to design a comprehensive antiretroviral data warehouse that will integrate data from several operational sources which are all associated with HIV/AIDS.

  3. Population uptake of antiretroviral treatment through primary care in rural South Africa

    Directory of Open Access Journals (Sweden)

    Bärnighausen Till W

    2010-09-01

    Full Text Available Abstract Background KwaZulu-Natal is the South African province worst affected by HIV and the focus of early modeling studies investigating strategies of antiretroviral treatment (ART delivery. The reality of antiretroviral roll-out through primary care has differed from that anticipated and real world data are needed to inform the planning of further scaling up of services. We investigated the factors associated with uptake of antiretroviral treatment through a primary healthcare system in rural South Africa. Methods Detailed demographic, HIV surveillance and geographic information system (GIS data were used to estimate the proportion of HIV positive adults accessing antiretroviral treatment within northern KwaZulu-Natal, South Africa in the period from initiation of antiretroviral roll-out until the end of 2008. Demographic, spatial and socioeconomic factors influencing the likelihood of individuals accessing antiretroviral treatment were explored using multivariable analysis. Results Mean uptake of ART among HIV positive resident adults was 21.0% (95%CI 20.1-21.9. Uptake among HIV positive men (19.2% was slightly lower than women (21.8%, P = 0.011. An individual's likelihood of accessing ART was not associated with level of education, household assets or urban/rural locale. ART uptake was strongly negatively associated with distance from the nearest primary healthcare facility (aOR = 0.728 per square-root transformed km, 95%CI 0.658-0.963, P = 0.002. Conclusions Despite concerns about the equitable nature of antiretroviral treatment rollout, we find very few differences in ART uptake across a range of socio-demographic variables in a rural South African population. However, even when socio-demographic factors were taken into account, individuals living further away from primary healthcare clinics were still significantly less likely to be accessing ART

  4. An information system to manage the rollout of the antiretroviral treatment programme in the Free State.

    Science.gov (United States)

    Kotzé, J E; McDonald, T

    2010-06-01

    The Acquired Immune Deficiency Syndrome epidemic, caused by the Human Immunodeficiency Virus, is a global crisis which threatens development gains, economies, and societies. Within sub-Saharan Africa, where the epidemic began the earliest and the HIV prevalence is the highest, African countries have death rates not seen before. In South Africa the epidemic has a devastating impact which creates profound suffering on individuals and their families, and the impact on the socio-economic level is of great concern. The eradication of HIV/AIDS represents one of humanity's greatest challenges, which requires co-operation and comprehensive collaboration between many different role players. In this endeavour clinical information plays a major role. To combat the effect of the disease, the Free State Department of Health started with the provisioning of antiretroviral therapy in the public health sector. The objective of this paper was to address the challenges they faced in order to develop and implement an information system to manage the rollout of antiretroviral treatment effectively. They started with a paper-based system to collect vital information. It was followed by a palm computer project that was initiated to electronically capture the data collected by the paper-based system. This system was then replaced by a comprehensive Hospital and Clinic Information System which was acquired and customised for the antiretroviral data collection process. Research partners developed a standalone antiretroviral data warehouse for collecting information associated with the monitoring and evaluation of the Free State antiretroviral and HIV/ AIDS treatment programme. The data warehouse successfully produced several management information reports to the antiretroviral management team. A need was identified to design a comprehensive antiretroviral data warehouse that will integrate data from several operational sources which are all associated with HIV/AIDS.

  5. HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area

    Directory of Open Access Journals (Sweden)

    Inés Zapiola

    2016-12-01

    Full Text Available The study aimed to determine the prevalence of antiretroviral resistance associated mutations in HIV-1 infected pregnant woman treated in Buenos Aires metropolitan area (period 2008-2014. A total of 136 women with viral load = 500 copies/ml were included: 77 (56.6% were treatment-naïve and 59 (43.4% were antiretroviral-experienced patients either with current (n: 24 or previous (n = 35 antiretroviral therapy. Genotypic baseline resistance was investigated in plasma of antiretroviral-naïve patients and antiretroviral-experienced patients. The resistance mutations were identified according to the lists of the World Health Organization and the International Antiviral Society, respectively. Frequencies of resistance associated mutations detected in 2008-2011 and 2012-2014 were compared. A total of 37 (27.2% women presented at least one resistance associated mutation: 25/94 (26.5% in 2008-2011 and 12/42 (28.5% in 2012-2014 (p > 0.05. Among naïves, 15 (19.5% had at least one mutation: 10/49 (20.4% in the period 2008-2011 and 5/28 (17.8% in 2012-2014 (p > 0.05. The resistance mutations detected in naïves were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. In antiretroviral experienced patients, 22/59 (37.3% had at least one resistance mutation. This study demonstrates a high frequency of resistance associated mutations which remained stable in the period analyzed. These levels suggest an increased circulation of HIV-1 antiretroviral resistant strains in our setting compared to previous reports from Argentina

  6. Antiretroviral treatment induced catatonia in 16-year-old boy

    Directory of Open Access Journals (Sweden)

    Anand Lingeswaran

    2014-01-01

    Full Text Available We present a 16-year-old boy, who had presented to us with catatonic features of mutism, withdrawal, passive negativism, grimacing, gesturing, echopraxia, and excitement of 5 days duration while taking antiretroviral therapy (ART for a period of 2 years. He had history of birth asphyxia and acquired HIV infection from his father when the same syringe and needle was used on both of them in a medical setting where the father and son had consulted for treatment of pyrexia of unknown origin. He was the eldest of a three children family in which the biologic father had acquired HIV through extramarital sexual contact with HIV-infected sex workers but was unaware of his HIV positive status till our patient, the 16-year-old was admitted and treated for pulmonary tuberculosis at 14 years of age. The boy′s mother had only acquired HIV after having three children with the HIV-positive husband, thus leaving the other two children HIV negative. The catatonia completely resolved within 2 days after the ART was withheld, and risperidone 1 mg twice a day was prescribed. This case highlights the risks of ART and breach of universal precautions.

  7. Barriers to initiation of antiretrovirals during antituberculosis therapy in Africa.

    Directory of Open Access Journals (Sweden)

    Dominique J Pepper

    Full Text Available BACKGROUND: In the developing world, the principal cause of death among HIV-infected patients is tuberculosis (TB. The initiation of antiretroviral therapy (ART during TB therapy significantly improves survival, however it is not known which barriers prevent eligible TB patients from initiating life-saving ART. METHOD: Setting. A South African township clinic with integrated tuberculosis and HIV services. Design. Logistic regression analyses of a prospective cohort of HIV-1 infected adults (≥18 years who commenced TB therapy, were eligible for ART, and were followed for 6 months. FINDINGS: Of 100 HIV-1 infected adults eligible for ART during TB therapy, 90 TB patients presented to an ART clinic for assessment, 66 TB patients initiated ART, and 15 TB patients died. 34% of eligible TB patients (95%CI: 25-43% did not initiate ART. Male gender and younger age (<36 years were associated with failure to initiate ART (adjusted odds ratios of 3.7 [95%CI: 1.25-10.95] and 3.3 [95%CI: 1.12-9.69], respectively. Death during TB therapy was associated with a CD4+ count <100 cells/µL. CONCLUSION: In a clinic with integrated services for tuberculosis and HIV, one-third of eligible TB patients--particularly young men--did not initiate ART. Strategies are needed to promote ART initiation during TB therapy, especially among young men.

  8. Common mental health problems and antiretroviral therapy adherence.

    Science.gov (United States)

    Nel, Adriaan; Kagee, Ashraf

    2011-11-01

    This paper reviews the literature on various mental health problems and their impact on adherence to antiretroviral therapy (ART). Depression, anxiety disorders, and disorders related to substance abuse were identified as key role-players influencing adherence. The severity of symptoms related to these disorders was found to be inversely related to ART adherence, with the possible exception of post-traumatic stress disorder (PTSD). PTSD was found to have both positive and negative implications for adherence, with severity of symptoms ranging from health-protective concern to disabling distress. Possible solutions aimed at addressing the adverse effects of mental health problems on adherence are discussed. Routine screening in ART settings is suggested in settings where follow-up of positive screen scores are possible, along with the necessary interventions to resolve the disorder of concern. Suggested interventions include utilising psychotherapeutic treatment, both in isolation and in conjunction with medication, to address mental health problems. Furthermore, finding effective ways of marshalling social support is recommended for ensuring optimal adherence, and possibly mitigating the adverse effects of mental health problems. Further research is needed to find feasible ways of identifying, assessing and treating patients with mental health problems in resource-constrained settings where HIV prevalence is highest.

  9. Oropharyngeal Candidiasis in the Era of Antiretroviral Therapy

    Science.gov (United States)

    Thompson, George R.; Patel, Payal K.; Kirkpatrick, William R.; Westbrook, Steven D.; Berg, Deborah; Erlandsen, Josh; Redding, Spencer W.; Patterson, Thomas F.

    2009-01-01

    Oropharyngeal candidiasis (OPC) remains a common problem in the HIV-infected population despite the availability of antiretroviral therapy (ART). Although Candida albicans is the most frequently implicated pathogen, other Candida spp. may also cause infection. The emergence of antifungal resistance within these causative yeasts, especially in patients with recurrent oropharyngeal infection or with long-term use of antifungal therapies, requires a working knowledge of alternative antifungal agents. Identification of the infecting organism and antifungal susceptibility testing enhances the ability of clinicians to prescribe appropriate antifungal therapy. Characterization of the responsible mechanisms has improved our understanding of the development of antifungal resistance and could enhance the management of these infections. Immune reconstitution has been shown to reduce rates of oropharyngeal candidiasis but few studies have evaluated the current impact of ART on the epidemiology of oropharyngeal candidiasis and antifungal resistance in these patients. Preliminary results from an ongoing clinical study showed that in patients with advanced AIDS oral yeast colonization was extensive, occurring in 81.1% of the 122 patients studied and symptomatic infection occurred in a third. In addition, resistant yeasts were still common occurring in 25.3% of patients colonized with yeasts or with symptomatic infection. Thus, oropharyngeal candidasis remains a significant infection in advanced AIDS even with ART. Current knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and mechanisms of antifungal resistance observed in oropharyngeal candidiasis are important in managing patients with this infection and are the focus of this review. PMID:20156694

  10. The Impact of Antiretroviral Therapy on Lung Immunology.

    Science.gov (United States)

    Cribbs, Sushma K; Fontenot, Andrew P

    2016-04-01

    Despite the introduction of antiretroviral therapy (ART), human immunodeficiency virus-1 (HIV) continues to cause a major impact worldwide. HIV-induced lung disease continues to represent a significant source of morbidity and mortality, although the spectrum of pulmonary diseases has changed. HIV significantly affects the lung, causing acute and chronic cellular changes in the alveolar space. The impact of ART on lung immunology still needs to be fully elucidated. Similar to the periphery, ART affects HIV viral load and reconstitutes CD4(+) T cells in the lung. ART has been associated with significant decreases in bronchoalveolar lavage lymphocytes and increases in B-cell numbers and functionality, resulting in improved immune responses to vaccinations. There are substantial clinical implications of these ART-induced alterations, including the emergence of immune reconstitution inflammatory syndrome and the increased incidences of noninfectious lung diseases, such as lung cancer and chronic obstructive lung disease. There continues to be many unanswered questions regarding the effects of ART on lung health and, in particular, the immune system. Growing knowledge in this area will hopefully diminish the incidence of these noninfectious lung diseases and further improve the health of individuals living with HIV.

  11. Antiretroviral treatment reverses HIV-associated anemia in rural Tanzania

    Directory of Open Access Journals (Sweden)

    Gundersen Svein G

    2011-07-01

    Full Text Available Abstract Background HIV-associated anemia is common and associated with poor prognosis. However, its response to antiretroviral treatment (ART in rural Africa is poorly understood. Methods HIV-infected adults (≥15 years who enrolled in HIV care at Haydom Lutheran Hospital in northern Tanzania were included in the study. The effect of ART (zidovudine/stavudine + lamivudine + efavirenz/nevirapine on HIV-associated anemia was studied in a subset of patients who were anemic at the time they started ART and had a follow-up hemoglobin measurement 12 months later. Pregnant women were excluded from the study, as were women who had given birth within the past 6 weeks. Anemia was defined as hemoglobin Results At enrollment, mean hemoglobin was 10.3 g/dL, and 649 of 838 patients (77.4% were anemic. Of the anemic patients, 254 (39.1% had microcytosis and hypochromia. Among 102 patients who were anemic at ART initiation and had a follow-up hemoglobin measurement after 12 months, the mean hemoglobin increased by 2.5 g/dL (P Conclusions Most patients had anemia at enrollment, of whom nearly 40% had microcytosis and hypochromia suggestive of iron deficiency. The mean hemoglobin increased significantly in patients who received ART, but one third were still anemic 12 months after ART initiation indicating that additional interventions to treat HIV-associated anemia in rural Africa might be warranted, particularly in patients with microcytosis and those treated with zidovudine.

  12. Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients

    DEFF Research Database (Denmark)

    Ceccherini-Silberstein, Francesca; Cozzi-Lepri, Alessandro; Ruiz, Lidia;

    2007-01-01

    A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated.......A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated....

  13. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    DEFF Research Database (Denmark)

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas

    2013-01-01

    BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the set...

  14. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    NARCIS (Netherlands)

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P; Li, Xiuhong; Kingsley, Lawrence A; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A; Reiss, Peter; Weber, Rainer; Bucher, Heiner C; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E; Schölvinck, Elisabeth H.

    2013-01-01

    BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the settin

  15. Naive and memory human