Detection and quantification of proviral HIV-1 184 M/V in circulating CD4(+) T cells of patients on HAART with a viremia less than 1000 copies/ml

DEFF Research Database (Denmark)

Mohey, Rajesh; Jørgensen, Anne Louise; Møller, Bjarne K

2005-01-01

and incorporation of resistant forms in the long-lived CD4+ T cellular DNA compartment is not clear. Objective To investigate the relationship between lamivudine associated mutant-type 184V and the wild-type 184M proviral forms in the circulating CD4+ T cells of patients and low-level viremia. Study design Cross-sectional......Background Highly active anti-retroviral therapy (HAART) effectively reduces HIV replication but does not completely hinder it. Sub-optimal therapy leads to HIV resistance to the drugs administered. However, the role of low-level viremia (viral-load less than 1000 copies/ml) on mutation genesis...... study of 50 patients on long-term HAART, with a viremia of less than 1000 copies/ml. Patients were stratified into three groups; on lamivudine, group I (viral load

reasons for change of anti-retroviral therapy (art) drugs

African Journals Online (AJOL)

2013-12-01

Dec 1, 2013 ... these factors that have a bearing on compliance and success of treatment. Objective: To determine ... Steven Johnson Syndrome, pancreatitis) and probable failure of to HAART. CD4+ cell ... Indeed,. HAART has transformed HIV disease into a chronic .... Factors independently associated with a greater risk.

Short Report: Worsening and unmasking of tuberculosis in HIV-1 ...

African Journals Online (AJOL)

Objectives: To determine the proportion of patients developing active tuberculosis (TB) versus that of patients who experience worsening of TB, after initiating highly active anti retroviral therapy (HAART). Methods: Charts of HAART naïve patients with or without clinically active TB who consecutively commenced HAART at ...

Molecular Mechanisms in Activation of Latent HIV-1

NARCIS (Netherlands)

H. Rafati (Haleh)

2014-01-01

markdownabstract__Abstract__ Finding a cure for the human immunodeficiency virus type 1 (HIV-1) is extremely challenging. Development of highly active anti-retroviral therapy (HAART), transformed HIV-1 infection from an acute syndrome into chronic disease. Although using HAART results in

Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

Directory of Open Access Journals (Sweden)

Arun K. Nalla

2016-03-01

Full Text Available Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC. Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.

Mother-to-child transmission of human immunodeficiency virus (HIV) among HIV-infected pregnant women on highly active anti-retroviral therapy with premature rupture of membranes at term.

Science.gov (United States)

Eleje, George Uchenna; Edokwe, Emeka Stephen; Ikechebelu, Joseph Ifeanyichukwu; Onubogu, Chinyere Ukamaka; Ugochukwu, Ebele Francesca; Okam, Princeston Chukwuemeka; Ibekwe, Adaobi Maryann

2018-01-01

To determine mother-to-child transmission (MTCT) rate and associated risk factors of human immune-deficiency virus (HIV) among HIV-infected pregnant women with term premature rupture of membranes (PROM) in comparison with those without PROM at term. All optimally managed HIV-positive pregnant women of Nnamdi Azikiwe University Teaching Hospital, on highly active anti-retroviral therapy (HAART) who had PROM at term were enrolled. Maternal HIV-1 viral load was not assessed. Follow up was for a minimum of 18 months for evidence of HIV infection. Of the 121 women with PROM at term, 46 (38.0%) were HIV sero-positive, 22/46 (47.8%) of which had their babies followed up till 18 months. The mean latency period was 10.5 ± 5.3 h in PROM group. Apart from duration of PROM (OR = 0.01; 95%CI = 0.00-0.13; p  0.05). Of the 22 (47.8%) babies followed-up in the PROM group and 13 in non-PROM group, none tested positive to HIV, given an MTCT rate of 0%. MTCT rate was 0% following term PROM and in women without PROM. Since maternal HIV-1 viral load was not assessed, we need to be critical while interpreting the findings.

An audit on virological efficacy of anti-retroviral therapy in a specialist infectious disease clinic.

LENUS (Irish Health Repository)

Reyad, A

2009-06-01

We have assessed the efficacy of anti retroviral therapy (ART) using undetectable viral load (VL) (<50 RNA copies\\/ml) as a marker of virological success, in patients who have Human Immunodeficiency Virus (HIV) attending the Department of Infectious Disease. A cross-sectional review of patients\\' case notes was used to obtain their demographics and treatment details. 79% (253) of the hospital case notes of clinic population was available for analysis, which represents 90% of those receiving ART in the clinic. 166\\/253 of the cohort were receiving treatment at the time of this study and 95% (157\\/166) of these were on treatment for greater than 6 months. The total virological success rate is 93%, which is comparable to other centres and are as good as those from published clinical trials. 56% of those on therapy who have virological failure were Intravenous Drug Users (IVDUs). Case by case investigation for those with treatment failure is warranted.

Fatores de risco para a não adesão ao tratamento com terapia antiretroviral altamente eficaz Factores de riesgo para la no-adherencia al tratamiento con terapia anti-retroviral altamente eficiente Risk factors for non-compliance to treatment with highly effective antiretroviral therapy

Directory of Open Access Journals (Sweden)

Maria Rosa Ceccato Colombrini

2008-09-01

Full Text Available O estudo objetivou: mensurar a prevalência de não-adesão à terapia anti-retroviral altamente eficaz (HAART em pacientes com AIDS; identificar se alguns fatores relacionados na literatura estavam associados com a não-adesão; estabelecer o valor preditivo dos fatores associados à não-adesão à HAART. Foi realizado um estudo analítico de prevalência (N=60. Foram considerados os três dias anteriores à entrevista e os pacientes classificados como aderentes quando ingeriam 95% ou mais do total de comprimidos prescritos por dia. A adesão foi de 73,3%. A análise de regressão logística multivariada indicou que indivíduos da raça negra apresentaram 6,48 vezes mais risco de não-adesão; aqueles que apresentaram ausência de efeito colateral tiveram um risco 7,6 vezes maior, e a cada comprimido ingerido o risco foi de 1,12. A adesão observada foi maior que a encontrada na literatura. Os fatores sociodemográficos e culturais podem interferir na adesão à HAART.Objetivo del estudio: medir la prevalencia por falta de seguimiento al tratamiento anti-retroviral altamente eficaz (HAART en pacientes con SIDA; identificar si algunos factores relacionados en la bibliografía se encuentran asociados con la falta de seguimiento; establecer el valor preditivo de los factores asociados con la falta de seguimiento al HAART. Para lo cual fue realizado un estudio analitico de prevalencia (N=60, considerándose los tres días anteriores a la entrevista, donde aquellos pacientes con ingesta del 95% o más del total de comprimidos prescritos por día eran clasificados como seguidores del tratamiento. El seguimiento fue de 73,3%. El análisis de regresion logística multi-variable mostró que sujetos de raza negra presentaron 6,48 veces mayor riesgo de no continuar con el tratamiento; aquellos individuos sin efectos colaterales tuvieron un riesgo 7,6 veces mayor, asimismo, cada comprimido ingerido produjo un riesgo de 1,12. El seguimiento observado fue

Retroviral DNA Integration

Science.gov (United States)

2016-01-01

The integration of a DNA copy of the viral RNA genome into host chromatin is the defining step of retroviral replication. This enzymatic process is catalyzed by the virus-encoded integrase protein, which is conserved among retroviruses and LTR-retrotransposons. Retroviral integration proceeds via two integrase activities: 3′-processing of the viral DNA ends, followed by the strand transfer of the processed ends into host cell chromosomal DNA. Herein we review the molecular mechanism of retroviral DNA integration, with an emphasis on reaction chemistries and architectures of the nucleoprotein complexes involved. We additionally discuss the latest advances on anti-integrase drug development for the treatment of AIDS and the utility of integrating retroviral vectors in gene therapy applications. PMID:27198982

THE EVOLUTION OF ANTI-RETROVIRAL THERAPY IN NIGERIA ...

African Journals Online (AJOL)

HAART) remains the single most significant advance in the field of HIV research. The Clinical Pharmacology of drugs used in the treatment of the virus has undergone rapid evolution over the years. In 1983 the virus was simultaneously identified ...

Infecções oportunistas em pacientes com aids internados em um hospital universitário do sudeste do Brasil

OpenAIRE

Nobre, Vandack; Braga, Emanuella; Rayes, Abdunnabi; Serufo, José Carlos; Godoy, Pérsio; Nunes, Nívea; Antunes, Carlos Maurício; Lambertucci, José Roberto

2003-01-01

Opportunistic diseases in HIV-infected patients have changed since the introduction of highly active anti-retroviral therapy (HAART). This study aims at evaluating the frequency of associated diseases in patients with AIDS admitted to an university hospital of Brazil, before and after HAART. The medical records of 342 HIV-infected patients were reviewed and divided into two groups: group 1 comprised 247 patients before HAART and, group 2, 95 patients after HAART. The male-to-female rate dropp...

Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection

DEFF Research Database (Denmark)

Stylianou, E; Aukrust, P; Bendtzen, K

2000-01-01

-infected patients had raised levels of both IP-10 and IFN-alpha compared with healthy controls (n = 19), with particularly high levels in advanced disease. HAART induced a marked decrease in levels of both IFN-alpha, neopterin and IP-10, though not to normal concentrations. In contrast, IFN-gamma levels were low...

The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive individuals

Directory of Open Access Journals (Sweden)

Vogel M

2010-03-01

Full Text Available Abstract Objective This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated. Methods Multicenter, partially randomized, controlled clinical trial. HIV-negative and -positive patients with chronic HCV infection were treated with pegylated interferon alfa-2a and ribavirin (800 - 1200 mg/day for 24 - 48 weeks in one of four treatment arms: HIV-negative (A, HIV-positive without HAART (B and HIV-positive on HAART (C. Patients within arm C were randomized to receive open label either a nucleoside containing (C1 or a nucleoside free HAART (C2. Results 168 patients were available for analysis. By intent-to-treat analysis similar sustained virological response rates (SVR, negative HCV-RNA 24 weeks after the end of therapy were observed comparing HIV-negative and -positive patients (54% vs. 54%, p = 1.000. Among HIV-positive patients SVR rates were similar between patients off and on HAART (57% vs. 52%, p = 0.708. Higher SVR rates were observed in patients on a nucleoside free HAART compared to patients on a nucleoside containing HAART, though confounding could not be ruled out and in the intent-to-treat analysis the difference was not statistically significant (64% vs. 46%, p = 0.209. Conclusions Similar response rates for HCV therapy can be achieved in HIV-positive and -negative patients. Patients on nucleoside free HAART reached at least equal rates of sustained virological response compared to patients on standard HAART.

Nigella Sativa Concoction induced sustained seroreversion in HIV ...

African Journals Online (AJOL)

African Journal of Traditional, Complementary and Alternative Medicines ... Abstract. Nigella sativa had been documented to possess many therapeutic functions in medicine but the least expected is sero-reversion in HIV infection which is very rare despite extensive therapy with highly active anti-retroviral therapy (HAART).

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African Journals Online (AJOL)

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with the most promise are angiotensin-converting enzyme inhibitors and antiretroviral medications. Role of steroids ... The patient was treated with HAART (Highly active anti retroviral therapy) ..... Burns GC, Paul SK, Toth IR, Sivak SL: Effect of.

The clinical spectrum and cost implications of hospitalised HIV ...

African Journals Online (AJOL)

children in the pre-HAART (highly active anti-retroviral therapy) era were hospitalised more ..... would include travel costs and reduced family income due to absence ... We declare that we have no financial or personal relationship(s) which.

CD4 + CELL RESPONSE TO ANTI-RETROVIRAL THERAPY (ARTs ...

African Journals Online (AJOL)

enhances immunity by sustained HIV- viral suppression, increase in CD4+ cell count and immune restoration. ... Seventy three (70.9%) of patients still had immune depletion with low CD4+ cell counts at one year of receiving HAART. ..... homeostasis and function in advanced HIV disease. Science 1997; 277: 112- 116. 7.

[Effect of highly active anti-retroviral therapy on prevention of mother to child transmission of HIV and on infant growth and development].

Science.gov (United States)

He, Yan; Luo, Yan; Ding, Yi-ling; Zheng, Yu-huang; Li, Jing; Huang, Jian; Li, Jie-min

2011-10-01

To identify the effect of highly active anti-retroviral therapy (HAART) on prevention of mother to child transmission (PMTCT) of HIV and on infant growth and development. A total of 16 HIV-infected women or pregnant women selected in this study received HAART before or 18 - 24 weeks after pregnancy. The treatment included taking Zidovudine (AZT) 0.3 g each time, twice a day, Lamivudine (3TC) 0.3 g each time, once a day and Nevirapine (NVP) 0.2 g each time, twice a day or Efavirenz (EFV) 0.6 g each time, once a day, as well as labor intervention and artificial feeding. The growth index for 17 infants from HIV-infected mothers (experimental group) and 16 normal infants (control group) were observed for 18 months. Neonatal hemoglobin (Hb), liver and kidney function, serum iron and calcium were detected at neonatal period and at 12(th) month, respectively. All the pregnant women were in good conditions and had tolerance with HAART. The birth weight, length and Apgar score of the newborns in the experimental group were (3.5 ± 0.9) kg, (54.2 ± 3.8) cm and 7 - 10 scores respectively, however those in the control group were (3.6 ± 0.8) kg, (55.6 ± 3.6) cm and 8 - 10 scores (t(weight) = 1.01, t(length) = 6.98, P > 0.05). Weight and length of infants in experimental group were (9.36 ± 1.8) kg and (76.3 ± 2.7) cm at 12(th) month, while those in control group were (9.86 ± 2.5) kg and (76.8 ± 2.9) cm (t(weight) = 0.83, t(length) = 1.00, P > 0.05). The level of Hb in experimental group was (126.2 ± 16.7) g/L, and was (148.6 ± 20.5) g/L in control group (t = -5.89, P = 0.11). At 12(th) month, the levels of Hb and the total bilirubin (TB) were (125.9 ± 19.8) g/L and (11.7 ± 3.5) µmol/L in experimental group; and those in the control group were (130.1 ± 18.7) g/L and (13.2 ± 3.7) µmol/L (t(Hb) = -3.82, t(TB) = -2.14, P > 0.05). Serum iron and calcium were (25.4 ± 5.7) µmol/L and (26.4 ± 7.2) µmol/L at neonatal period and were (2.3 ± 0.6) mol/L and (2.8 ± 0

Long-term effectiveness of highly active antiretroviral therapy (HAART) in perinatally HIV-infected children in Denmark

DEFF Research Database (Denmark)

Bracher, Linda; Valerius, Niels Henrik; Rosenfeldt, Vibeke

2007-01-01

children treated with HAART. Initial HAART included 2 nucleoside reverse-transcriptase inhibitors in combination with either a protease inhibitor (n =38) or a non-nucleoside reverse-transcriptase inhibitor (n =12). 19 (39%) patients were previously treated with mono- or dual therapy. Baseline......The long-term impact of highly active antiretroviral therapy (HAART) on HIV-1 infected children is not well known. The Danish Paediatric HIV Cohort Study includes all patients ... characteristics were median CD4 percentage 14% and HIV-RNA viral load 4.9 log(10). Within the first 12 weeks of therapy approximately 60% achieved HIV-RNA viral load children changed the components of HAART. The proportion of children with CD4...

Risk factors for death in HIV-infected adult African patients receiving anti-retroviral therapy.

Science.gov (United States)

Siika, A M; Wools-Kaloustian, K; Mwangi, A W; Kimaiyo, S N; Diero, L O; Ayuo, P O; Owino-Ong'or, W D; Sidle, J E; Einterz, R M; Yiannoutsos, C T; Musick, B; Tierney, W M

2010-11-01

To determine risk factors for death in HIV-infected African patients on anti-retroviral therapy (ART). Retrospective Case-control study. The MOH-USAID-AMPATH Partnership ambulatory HIV-care clinics in western Kenya. Between November 2001 and December 2005 demographic, clinical and laboratory data from 527 deceased and 1054 living patients receiving ART were compared to determine independent risk factors for death. Median age at ART initiation was 38 versus 36 years for the deceased and living patients respectively (p100/mm3 (HR=1.553. 95% CI (1.156, 2.087), p<0.003). Patients attending rural clinics had threefold higher risk of dying compared to patients attending clinic at a tertiary referral hospital (p<0.0001). Two years after initiating treatment fifty percent of non-adherent patients were alive compared to 75% of adherent patients. Male gender, WHO Stage and haemoglobin level <10 grams% were associated with time to death while age, marital status, educational level, employment status and weight were not. Profoundly immunosuppressed patients were more likely to die early in the course of treatment. Also, patients receiving care in rural clinics were at greater risk of dying than those receiving care in the tertiary referral hospital.

Retroviral rebound syndrome after treatment discontinuation in a 15 year old girl with HIV attracted through mother-to-child transmission: case report

OpenAIRE

Gisslén Magnus; Friman Vanda

2007-01-01

Abstract A case of a 15 year old girl with retroviral rebound syndrome after discontinuation of highly active antiretroviral treatment (HAART) due to side effects is presented. The patient was transmitted with HIV at birth by her mother. She had recovered from severe AIDS after HAART was initiated five years earlier. This is the first case reported in the literature of retroviral rebound syndrome in a vertically transmitted HIV-infected patient.

Outcomes of human immunodeficiency virus-infected children after anti-retroviral therapy in Malaysia.

Science.gov (United States)

Moy, Fong Siew; Fahey, Paul; Nik Yusoff, Nik K; Razali, Kamarul A; Nallusamy, Revathy

2015-02-01

To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART). Retrospective and prospective data collected through March 2009 from children in four different states in Malaysia enrolled in TREAT Asia's Pediatric HIV Observational Database were analysed. Of 347 children in the cohort, only 278 (80.1%) were commenced on ART. The median CD4 count and median age at baseline prior to ART was 272 cells/μL and 4.2 years (interquartile range (IQR): 1.4, 7.4 years), respectively. The median duration of follow-up was 3.7 years (IQR: 1.8, 6.0) with 32 deaths giving a crude mortality rate of 2.86 per 100 child-years. The mortality rate highest in the first 6 months of ART was 10.62 per 100 child-years and declined to 1.83 per 100 child-years thereafter. On univariate analyses, only baseline median CD4 percentage, weight for age z score, height for age z score and anaemia were significantly associated with mortality. Upon including all four of these predictors into a single multivariate model, only weight for age z score remained statistically significantly predictive of mortality. Children commenced on ART had high mortality in the first 6 months especially in those with low CD4 percentage, wasting and anaemia. Poor nutritional status is an important independent predictor of mortality in this study. Besides initiating ART therapy, nutritional support and intervention must receive the utmost attention. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Outcome of surgery in post-cytomegalovirus retinal detachment: Experience before and in the era of highly active anti-retroviral therapy in Indian eyes

Directory of Open Access Journals (Sweden)

Ramandeep Singh

2013-01-01

Full Text Available Purpose: To evaluate the outcome of surgery for cytomegalovirus associated retinal detachment (CMVRD in human immunodeficiency virus (HIV-infected patients in pre-highly active antiretroviral therapy (HAART and HAART era in Indian eyes. Materials and Methods: Retrospective, we reviewed medical records of all consecutive HIV patients, who underwent surgical repair for CMVRD from July 1998 to June 2011. We divided patients into two groups, i.e. group 1, pre HAART era and group 2, HAART era. We compared two groups for various parameters like visual outcome, surgical success, additional procedures, follow-up, etc., Results: Twenty-eight eyes of 26 patients were included; 12 eyes of the 11 patients in group 1 and 16 eyes of the 15 patients in group 2. Significant visual acuity improvement was seen in both groups. Complete anatomic success was seen in 11 eyes in group 1 and 15 eyes in group 2. One additional procedure in group 1 and 29 additional procedures were done in group 2. A mean follow-up was 16 months in group 1 and 41 months in group 2. Conclusion: There was no difference in outcome in pre-HAART and HAART group, except for longer follow-up and additional surgical procedures in HAART group.

Access to highly active antiretroviral therapy (HAART) in the WHO European Region 2003-2005

DEFF Research Database (Denmark)

Bollerup, Annemarie R; Donoghoe, Martin C; Lazarus, Jeff

2008-01-01

To assess changes in access to highly active antiretroviral therapy (HAART) between the end of 2002 and the end of 2005, and to review the capacity for further HAART scale-up in the then 52 Member States of the WHO European Region....

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.

Gaps in the Implementation of Anti-Retroviral Treatment: A Case for ...

African Journals Online (AJOL)

... of Anti-Retroviral Treatment: A Case for Addressing Gender and Mental Health ... to score successes in ensuring adherence to ART as well as reducing new HIV ... lack of established clinical infrastructure, negative social stigma and the cost ...

Anti-retroviral therapy fails to restore the severe Th-17: Tc-17 imbalance observed in peripheral blood during simian immunodeficiency virus infection.

Science.gov (United States)

Kader, M; Bixler, S; Piatak, M; Lifson, J; Mattapallil, J J

2009-10-01

Human immuno deficiency virus and simian immunodeficiency virus infections are characterized by a severe loss of Th-17 cells (IL-17(+)CD4(+) T cells) that has been associated with disease progression and systemic dissemination of bacterial infections. Anti-retroviral therapy (ART) has led to repopulation of CD4(+) T cells in peripheral tissues with little sustainable repopulation in mucosal tissues. Given the central importance of Th-17 cells in mucosal homeostasis, it is not known if the failure of ART to permanently repopulate mucosal tissues is associated with a failure to restore Th-17 cells that are lost during infection. Dynamics of alpha4(+)beta7(hi) CD4(+) T cells in peripheral blood of SIV infected rhesus macaques were evaluated and compared to animals that were treated with ART. The frequency of Th-17 and Tc-17 cells was determined following infection and after therapy. Relative expression of IL-21, IL-23, and TGFbeta was determined using Taqman PCR. Treatment of SIV infected rhesus macaques with anti-retroviral therapy was associated with a substantial repopulation of mucosal homing alpha4(+)beta7(hi)CD4(+) T cells in peripheral blood. This repopulation, however, was not accompanied by a restoration of Th-17 responses. Interestingly, SIV infection was associated with an increase in Tc-17 responses (IL-17(+)CD8(+) T cells) suggesting to a skewing in the ratio of Th-17: Tc-17 cells from a predominantly Th-17 phenotype to a predominantly Tc-17 phenotype. Surprisingly, Tc-17 responses remained high during the course of therapy suggesting that ART failed to correct the imbalance in Th-17 : Tc-17 responses induced following SIV infection. ART was associated with substantial repopulation of alpha4(+)beta7(hi) CD4(+) T cells in peripheral blood with little or no rebound of Th-17 cells. On the other hand, repopulation of alpha4(+)beta7(hi) CD4(+) T cells was accompanied by persistence of high levels of Tc-17 cells in peripheral blood. The dysregulation of Th-17

Structural dynamics of retroviral genome and the packaging.

Science.gov (United States)

Miyazaki, Yasuyuki; Miyake, Ariko; Nomaguchi, Masako; Adachi, Akio

2011-01-01

Retroviruses can cause diseases such as AIDS, leukemia, and tumors, but are also used as vectors for human gene therapy. All retroviruses, except foamy viruses, package two copies of unspliced genomic RNA into their progeny viruses. Understanding the molecular mechanisms of retroviral genome packaging will aid the design of new anti-retroviral drugs targeting the packaging process and improve the efficacy of retroviral vectors. Retroviral genomes have to be specifically recognized by the cognate nucleocapsid domain of the Gag polyprotein from among an excess of cellular and spliced viral mRNA. Extensive virological and structural studies have revealed how retroviral genomic RNA is selectively packaged into the viral particles. The genomic area responsible for the packaging is generally located in the 5' untranslated region (5' UTR), and contains dimerization site(s). Recent studies have shown that retroviral genome packaging is modulated by structural changes of RNA at the 5' UTR accompanied by the dimerization. In this review, we focus on three representative retroviruses, Moloney murine leukemia virus, human immunodeficiency virus type 1 and 2, and describe the molecular mechanism of retroviral genome packaging.

Influence of highly active antiretroviral therapy (HAART) on the ...

African Journals Online (AJOL)

This report is part of the ongoing highly active antiretroviral therapy (HAART) trial, 167 patients were enlisted, but current analysis was restricted to 107 patients that were about a year old on the programme. The baseline weight, CD4+ cell count and serum albumin of 59 males and 48 females age 15-60 years, were ...

Thyroid dysfunction in human immunodeficiency virus-infected children and its correlation with CD4 + T lymphocyte count

Directory of Open Access Journals (Sweden)

Satyakumar Thongam

2015-01-01

Full Text Available Context: Thyroid dysfunction has been reported in human immunodeficiency virus (HIV-infected individuals including children. Some studies have reported that thyroid dysfunction may be a marker of severity or progression of HIV. Aims: The aim was to study thyroid function in HIV-infected children with and without highly active anti-retroviral therapy (HAART. Settings and Design: Cross-sectional study carried out at a teaching hospital with Anti-Retroviral Therapy Centre (Centre of Excellence of National AIDS Control Organization. Subjects and Methods: Thyroid stimulating hormone (TSH, total thyroxine (T4, and total tri-iodothyronine (T3 were analyzed in 60 pediatric HIV cases: 30 on HAART and 30 HAART naive. Correlation of T3, T4, and TSH with CD4 count was assessed. Statistical Analysis Used: Data reported as mean ± standard deviation and as the number of cases and percentages. Comparison between groups was done by independent sample t-test and χ2 -test. Spearman′s correlation coefficient is used to assess the association between thyroid dysfunction and CD4 count. Results: Thyroid function abnormality was seen in five out of 30 patients in both patients on HAART or without HAART therapy. Among patients on HAART, three had hypothyroidism, and two had biochemical feature of sick euthyroid syndrome. Among the HAART naive group, sub-clinical hypothyroisim was seen in four, and one had biochemical feature of sick euthyroid syndrome. None of the patients had clinical features of thyroid dysfunction. There is a highly significant correlation (P = 0.01 between TSH and CD4 count. Conclusions: Thyroid dysfunction is quite common among pediatric HIV cases. An inverse correlation is seen between TSH and CD4 count indicating trend for hypothyroidism as HIV disease progress.

Cost-effectiveness of anti-retroviral therapy at a district hospital in southern Ethiopia

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Robberstad Bjarne

2009-07-01

Full Text Available Abstract Background As the resource implications of expanding anti-retroviral therapy (ART are likely to be large, there is a need to explore its cost-effectiveness. So far, there is no such information available from Ethiopia. Objective To assess the cost-effectiveness of ART for routine clinical practice in a district hospital setting in Ethiopia. Methods We estimated the unit cost of HIV-related care from the 2004/5 fiscal year expenditure of Arba Minch Hospital in southern Ethiopia. We estimated outpatient and inpatient service use from HIV-infected patients who received care and treatment at the hospital between January 2003 and March 2006. We measured the health effect as life years gained (LYG for patients receiving ART compared with those not receiving such treatment. The study adopted a health care provider perspective and included both direct and overhead costs. We used Markov model to estimate the lifetime costs, health benefits and cost-effectiveness of ART. Findings ART yielded an undiscounted 9.4 years expected survival, and resulted in 7.1 extra LYG compared to patients not receiving ART. The lifetime incremental cost is US$2,215 and the undiscounted incremental cost per LYG is US$314. When discounted at 3%, the additional LYG decreases to 5.5 years and the incremental cost per LYG increases to US$325. Conclusion The undiscounted and discounted incremental costs per LYG from introducing ART were less than the per capita GDP threshold at the base year. Thus, ART could be regarded as cost-effective in a district hospital setting in Ethiopia.

Structural dynamics of retroviral genome and the packaging

Directory of Open Access Journals (Sweden)

Yasuyuki eMiyazaki

2011-12-01

Full Text Available Retroviruses can cause diseases such as AIDS, leukemia and tumors, but are also used as vectors for human gene therapy. All retroviruses, except foamy viruses, package two copies of unspliced genomic RNA into their progeny viruses. Understanding the molecular mechanisms of retroviral genome packaging will aid the design of new anti-retroviral drugs targeting the packaging process and improve the efficacy of retroviral vectors. Retroviral genomes have to be specifically recognized by the cognate nucleocapsid (NC domain of the Gag polyprotein from among an excess of cellular and spliced viral mRNA. Extensive virological and structural studies have revealed how retroviral genomic RNA is selectively packaged into the viral particles. The genomic area responsible for the packaging is generally located in the 5’ untranslated region (5’ UTR, and contains dimerization site(s. Recent studies have shown that retroviral genome packaging is modulated by structural changes of RNA at the 5’ UTR accompanied by the dimerization. In this review, we focus on three representative retroviruses, Moloney murine leukemia virus (MoMLV, human immunodeficiency virus type 1 (HIV-1 and 2 (HIV-2, and describe the molecular mechanism of retroviral genome packaging.

A Comparison of the Diabetes Risk Score in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART and HAART-Naïve 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.

Access to highly active antiretroviral therapy (HAART) for women and children in the WHO European Region 2002-2006

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Stengaard, Annemarie Rinder; Lazarus, Jeff; Donoghoe, Martin C

2009-01-01

Objective. To assess the level of access to highly active antiretroviral therapy (HAART) for women and children in the WHO European Region. Methods. Analysis of data from three national surveys of 53 WHO European Member States. The comparative level of access to HAART for women and children was a...

Changing electrolyte and acido-basic profile in HIV-infected patients in the HAART era.

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Isnard Bagnis, Corinne; Du Montcel, Sophie Tezenas; Fonfrede, Michele; Jaudon, Marie Chantal; Thibault, Vincent; Carcelain, Guislaine; Valantin, Marc Antoine; Izzedine, Hassan; Servais, Aude; Katlama, Christine; Deray, Gilbert

2006-01-01

HIV-infected patients may develop a variety of underreported metabolic abnormalities that may be classified into HIVAN, specific HIV abnormalities, coincidental renal disorders and anti-retroviral-treatment-induced side effects. Our descriptive cross-sectional study evaluates the prevalence of electrolyte and acid base disorders in HIV patients in the HAART era in a tertiary care teaching hospital. All consecutive HIV-infected patients (n = 1,232) presenting at our Department of Infectious Disease over 3 months were included. All available biochemical data obtained at admission or on the day of the visit were analyzed. We identified risk factors for electrolyte and acid base disorders with univariate regression analysis and multivariate stepwise regression analysis. Variables tested for significance included age, sex, absolute CD4 and CD8 counts, hepatitis B and C antibodies, and use and type of anti-retroviral medication. Most frequent and clinically relevant abnormalities were hyperuricemia in 41.3%, hypophosphatemia in 17.2% and low bicarbonate level in 13.6% of HIV-tested patients. Plasma magnesium was out of the normal range in 38.9% and blood glucose in 25.3% of the tested patients. When CD4 count was below 200/mm3, 9.2% of tested patients experienced low serum calcium (vs. 0.5% if CD4 count >200/mm3, p 200/mm3, p 200/mm3, p < 0.0001). Protease inhibitor treatment was a significant risk factor of hyperuricemia (p < 0.003). Non-nucleoside reverse transcriptase inhibitor therapy was significantly associated with less hyperuricemia (OR = 0.6, 95% CI 0.38-0.96) and with hypophosphatemia (OR = 2.0, 95% CI 1.1-3.4). The profile of biochemical abnormalities in HIV-infected patients has changed, hyperuricemia and hypophosphatemia being the most prevalent. Causes are poorly understood. Interpretation of drug-induced side effects in the HIV patient is only meaningful if performed versus a control group of patients. Copyright 2006 S. Karger AG, Basel

Profiles of HIV-infected anti-retroviral therapy naïve children from Mumbai, India.

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Paranjpe, Supriya Mayur; Sarkate, Purva Pankaj; Ingole, Nayana Avinash; Raut, Shweta Sadanand; Mehta, Preeti Rajeev

2016-11-01

This study aimed to investigate the demographic profiles of human immunodifficiency virus (HIV) infected anti-retroviral therapy (ART) naïve children in our hospital and their relations to the clinical, immunological and nutritional status. A cross-sectional study was conducted in an Integrated Counselling and Testing Center (ICTC) at a tertiary care hospital in Mumbai. ART naïve HIV positive children were enrolled in the study. The demographic profiles, clinical features, immunological (CD4%/CD4 count) and nutritional status of these children were recorded. The agreement between clinical, immunological and nutritional staging was determined using Cohen's kappa test. In 192 HIV-infected ART naive children enrolled with a median age of 9 years (range 3 months-14 years), 97.4% acquired infection through vertical transmission. The most common clinical presentation was fever (39.6 %), followed by generalized lymphadenopathy (32.3%), cough (22.4%) and diarrhoea (9.9%). Tuberculosis was seen in 22.9% of the children. The agreement was fair between clinical and immunological staging, and slight between nutritional, immunological and clinical staging. Perinatal transmission is the most common mode of acquiring HIV infection in children. The Prevention of Parent to Child Transmission (PPTCT) program should be strengthened for lowering the transmission rate by providing extended ART to mothers during pregnancy and breast-feeding. Tuberculosis remains a major concern in HIV-infected children. The poor correlation between WHO clinical and immunological staging emphasizes the importance of making CD4 facilities available in HIV prevalent areas. Malnutrition cannot be used as a surrogate marker for predicting stage or severity as it is common at all stages of HIV disease.

Nonorgan-specific autoantibodies in HIV-infected patients in the HAART era.

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Iordache, Laura; Bengoufa, Djaouida; Taulera, Olivier; Rami, Agathe; Lascoux-Combe, Caroline; Day, Nesrine; Parrinello, Maguy; Sellier, Pierre-Olivier; Molina, Jean-Michel; Mahr, Alfred

2017-03-01

Nonorgan-specific autoantibodies (AAbs) are used for diagnosing autoimmune diseases but can also be detected in other conditions. We carried out a cross-sectional study with the aim to screen HIV1-infected patients in the era of highly active antiretroviral therapy (HAART) for AAbs and to analyze the association of their presence with hypergammaglobulinemia and immunovirological status.Blood samples from HIV1-infected patients without major concomitant illnesses followed in 2 hospitals in Paris, France were tested for immunovirological status, serum immunoglobulin G (IgG) level, antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigens (anti-ENAs), anticardiolipin (aCL), anti-β2glycoprotein1 (anti-β2GP1), and antineutrophil cytoplasmic antibodies (ANCAs). Clinically relevant AAbs were defined as ANAs with titers ≥1:160, anti-dsDNA or anti-ENA antibodies; aCL or anti-β2GP1 antibodies with a level ≥40 U/ml; and ANCAs reacting with proteinase 3 or myeloperoxidase.We included 92 patients (mean age 47 years, men 55%, sub-Saharan African background 55%, HAART 85%, mean CD4 lymphocyte count 611/mm, viral load < 40 copies/mL 74%). At least 1 AAb was detected in 45% of patients, mostly ANAs (33%) and ANCAs (13%); 12% had ≥1 clinically relevant AAb. Above-normal IgG levels were found in 71% of patients. We found an inverse association between the presence of ≥1 AAb and CD4 lymphocyte count (P = 0.03) and between above-normal IgG levels and duration of virological control (P = 0.02) and non-sub-Saharan African background (P = 0.001).In sum, in HIV1-infected patients without any major concomitant illness in the HAART era, the prevalence of AAbs remains high but AAb patterns leading to high suspicion of autoimmune diseases are rather uncommon. AAb presence is associated with reduced CD4 lymphocyte count but not hypergammaglobulinemia.

Anti-Retroviral Lectins Have Modest Effects on Adherence of Trichomonas vaginalis to Epithelial Cells In Vitro and on Recovery of Tritrichomonas foetus in a Mouse Vaginal Model

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Chatterjee, Aparajita; Ratner, Daniel M.; Ryan, Christopher M.; Johnson, Patricia J.; O’Keefe, Barry R.; Secor, W. Evan; Anderson, Deborah J.; Robbins, Phillips W.; Samuelson, John

2015-01-01

Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervical cells and on Tritrichomonas infections in a mouse model. We show that Trichomonas Asn-linked glycans (N-glycans), like those of HIV, bind the mannose-binding lectin (MBL) that is part of the innate immune system. N-glycans of Trichomonas and Tritrichomonas bind anti-retroviral lectins (cyanovirin-N and griffithsin) and the 2G12 monoclonal antibody, each of which binds HIV N-glycans. Binding of cyanovirin-N appears to be independent of susceptibility to metronidazole, the major drug used to treat Trichomonas. Anti-retroviral lectins, MBL, and galectin-1 cause Trichomonas to self-aggregate and precipitate. The anti-retroviral lectins also increase adherence of ricin-resistant mutants, which are less adherent than parent cells, to ectocervical cell monolayers and to organotypic EpiVaginal tissue cells. Topical application of either anti-retroviral lectins or yeast N-glycans decreases by 40 to 70% the recovery of Tritrichomonas from the mouse vagina. These results, which are explained by a few simple models, suggest that the anti-retroviral lectins have a modest potential for preventing or treating human infections with Trichomonas. PMID:26252012

Anti-Retroviral Lectins Have Modest Effects on Adherence of Trichomonas vaginalis to Epithelial Cells In Vitro and on Recovery of Tritrichomonas foetus in a Mouse Vaginal Model.

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Aparajita Chatterjee

Full Text Available Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervical cells and on Tritrichomonas infections in a mouse model. We show that Trichomonas Asn-linked glycans (N-glycans, like those of HIV, bind the mannose-binding lectin (MBL that is part of the innate immune system. N-glycans of Trichomonas and Tritrichomonas bind anti-retroviral lectins (cyanovirin-N and griffithsin and the 2G12 monoclonal antibody, each of which binds HIV N-glycans. Binding of cyanovirin-N appears to be independent of susceptibility to metronidazole, the major drug used to treat Trichomonas. Anti-retroviral lectins, MBL, and galectin-1 cause Trichomonas to self-aggregate and precipitate. The anti-retroviral lectins also increase adherence of ricin-resistant mutants, which are less adherent than parent cells, to ectocervical cell monolayers and to organotypic EpiVaginal tissue cells. Topical application of either anti-retroviral lectins or yeast N-glycans decreases by 40 to 70% the recovery of Tritrichomonas from the mouse vagina. These results, which are explained by a few simple models, suggest that the anti-retroviral lectins have a modest potential for preventing or treating human infections with Trichomonas.

Tenofovir-Based Highly Active Antiretroviral Therapy Is Associated with Superior CD4 T Cells Repopulation Compared to Zidovudine-Based HAART in HIV 1 Infected Adults

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Vitus Sambo Badii

2018-01-01

Full Text Available Tenofovir-based highly active antiretroviral therapy (HAART is one of the preferred first-line therapies in the management of HIV 1 infection. Ghana has since 2014 adopted this recommendation; however there is paucity of scientific data that reflects the safety and efficacy of the tenofovir-based therapy compared to zidovudine in the Ghanaian health system. This study sought to assess the comparative immune reconstitution potential between tenofovir and zidovudine-based HAART regimens, which includes lamivudine and efavirenz in combination therapy. It also aimed to investigate the adverse drug reactions/events (ADREs associated with pharmacotherapy with these agents in a total of 106 HAART naïve HIV patients. The study included 80 patients in the tenofovir cohort while 26 patients were on the zidovudine regimen. The occurrence of HIV comorbidities profile was assessed at diagnosis and throughout the study period. The baseline CD4 T cells count of the participants was also assessed at diagnosis and repeated at a median period of five months (range 4–6 months, after commencing treatment with either tenofovir- or zidovudine-based HAART. After five months of the HAART, the tenofovir cohort recorded higher CD4 T cell count change from baseline compared to the zidovudine cohort (p<0.0001. The patients on the tenofovir-based HAART and female sex however appeared to be associated with more multiple ADREs.

PDT in periodontal disease of HAART resistance patients

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Giovani, Elcio M.; Noro-Filho, Gilberto A.; Caputo, Bruno V.; Casarin, Renato; Costa, Claudio; Salgado, Daniela; Santos, Camila C.

2016-03-01

HIV/Aids patients present a change of microbiota associated with host immunodeficiency. Photodynamic therapy (PDT) showed as a promising and viable alternative in reducing microbiota. Present study evaluate effectiveness of photodynamic therapy in periodontal disease of AIDS patients with highly activity antiretroviral therapy (HAART) failure, measuring the clinical periodontal parameters and periodontal microbiota. Twelve patients with HARRT resistance (R group) divided into two groups (control and PDT) and 12 patients with no HAART resistance (NR group) divided into two groups (control and PDT). The results show the difference in baseline of CD4 cells count, NR group 640.0 +/- 176.2 cells/mm3 R group and 333.3 +/- 205.8 cells / mm3 (pperiodontal parameters (PD and CAL), PDT was more effective than the control group only in the NR group (p periodontal parameters between the both R groups (p>0.05%). Microbiological evaluation in R group presents a general reduction in the Aa at 3 and 6 months. Furthermore, demonstrated a reduction of Pg in all groups at 6 months and in R group at 3 months. The impact assessment of photodynamic therapy in patients with different levels of immunosuppression determined that the combination of mechanical periodontal treatment with photodynamic therapy in patients with HAART failure did not cause additional benefits. Therefore, PDT in this study could not been indicated in HAART resistance patients.

Retinal arterioles narrow with increasing duration of anti-retroviral therapy in HIV infection: a novel estimator of vascular risk in HIV?

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Sophia Pathai

Full Text Available HIV infection is associated with an increased risk of age-related morbidity mediated by immune dysfunction, atherosclerosis and inflammation. Changes in retinal vessel calibre may reflect cumulative structural damage arising from these mechanisms. The relationship of retinal vessel calibre with clinical and demographic characteristics was investigated in a population of HIV-infected individuals in South Africa.Case-control study of 491 adults ≥30 years, composed of 242 HIV-infected adults and 249 age- and gender-matched HIV-negative controls. Retinal vessel calibre was measured using computer-assisted techniques to determine mean arteriolar and venular diameters of each eye.The median age was 40 years (IQR: 35-48 years. Among HIV-infected adults, 87.1% were receiving highly active antiretroviral therapy (HAART (median duration, 58 months, their median CD4 count was 468 cells/µL, and 84.3% had undetectable plasma viral load. Unadjusted mean retinal arteriolar diameters were 163.67±17.69 µm in cases and 161.34±17.38 µm in controls (p = 0.15. Unadjusted mean venular diameters were 267.77±18.21 µm in cases and 270.81±18.98 µm in controls (p = 0.07. Age modified the effect of retinal arteriolar and venular diameters in relation to HIV status, with a tendency towards narrower retinal diameters in HIV cases but not in controls. Among cases, retinal arteriolar diameters narrowed with increasing duration of HAART, independently of age (167.83 µm 6 years, p-trend = 0.02, and with a HIV viral load >10,000 copies/mL while on HAART (p = 0.05. HIV-related venular changes were not detected.Narrowing of retinal arteriolar diameters is associated with HAART duration and viral load, and may reflect heightened inflammatory and pro-atherogenic states of the systemic vasculature. Measurement of retinal vascular calibre could be an innovative non-invasive method of estimating vascular risk in HIV-infected individuals.

AIDS-Related Non-Hodgkin's Lymphoma in the Era of Highly Active Antiretroviral Therapy

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Prakash Vishnu

2012-01-01

Full Text Available In economically developed countries, AIDS-related lymphoma (ARL accounts for a large proportion of malignances in HIV-infected individuals. Since the introduction of highly active anti-retroviral therapy (HAART in 1996, epidemiology and prognosis of ARL have changed. While there is a slight increase in the incidence of Hodgkin’s lymphoma in HIV-infected individuals, use of HAART has contributed to a decline in the incidence of non-Hodgkin’s lymphoma (NHL and also a decrease in the overall incidence of ARL. Strategies that employ HAART, improved supportive care, and the use of Rituximab with multi-agent chemotherapy have contributed to improved rates of complete remission and survival of patients with ARL that rival those seen in stage and histology matched HIV negative NHL patients. Most recent clinical trials demonstrate better outcomes with the use of rituximab in ARL. Tumor histogenesis (germinal center vs. non-germinal center origin is associated with lymphoma-specific outcomes in the setting of AIDS-related diffuse-large B cell lymphoma. High-dose chemotherapy (HDCT and autologous stem cell rescue (ASCT can be effective for a subset of patients with relapsed ARL. HIV sero-status alone should not preclude consideration of ASCT in the setting of ARL relapse. Clinical trials investigating the role of allogeneic hematopoietic stem cell transplant in ARL are currently underway.

Liver enzyme abnormalities and associated risk factors in HIV patients on efavirenz-based HAART with or without tuberculosis co-infection in Tanzania.

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Sabina Mugusi

Full Text Available To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI in HIV patients with or without TB co-infection.A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS. Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week, being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week than those receiving HAART alone (5.9%, 6.3 per 1000 person-week. Frequency of CYP2B6*6 allele (p = 0.03 and CYP2B6*6/*6 genotype (p = 0.06 was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI.Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians.

Influence of Age and Neurotoxic HAART Use on Frequency of HIV Sensory Neuropathy

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Olajumoke Oshinaike

2012-01-01

Full Text Available Background. Sensory neuropathy (SN is one of the most common AIDS-associated neurologic disorders especially in the era of highly active antiretroviral therapy (HAART. The aim of this study was to determine the prevalence of SN among highly-active-antiretroviral-therapy- (HAART- experienced and HAART-naïve HIV-positive individuals and to investigate the relationship to demographic, clinical, and laboratory factors. Methods. 323 patients with HIV infection (142 on HAART and 181 HAART naïve were enrolled in a cross-sectional neuropathy screening program. Data was collected using structured questionnaires which contained the brief peripheral neuropathy screening tool of AIDS Clinical Trial Group protocol. Neuropathy was defined by the presence of at least 1 clinical sign in a distal, symmetrical pattern. Patients were classified as symptomatic if they described aching, stabbing, or burning pain, paresthesia, or numbness in a similar distribution. Demographic, clinical, and laboratory details were documented as risk factors. Result. The prevalence of sensory neuropathy was 39.0% (126/323, (of which 29/126 (23% were symptomatic. Amongst those on HAART, 60/142 (42.3% had SN compared to 66/181 (36.5% HAART-naïve individuals (P=0.29. On multivariate analyses, the independent associations with SN were increasing age (P=0.03 and current exposure to stavudine (P=0.00. Gender (P=0.99 height (P=0.07 use of HAART (P=0.50, duration of HAART treatment (P=0.10, and lower CD4 count (P=0.12 were not associated with an increased SN risk. Conclusion. HIV SN remains common despite improved immunologic function associated with HAART and decreased neurotoxic HAART use. In this cross-sectional analysis, age and stavudine-based therapies were the independent risk factors.

Non-adherence to anti-retroviral therapy among HIV infected adults in Mon State of Myanmar

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Win Lei Aye

2017-05-01

Full Text Available Abstract Background The provision of Anti-Retroviral Therapy (ART was started in Myanmar in 2005 in collaboration with the National AIDS Program and the private sector. Successful clinical management of HIV-infected patients is subject to optimal adherence. The aim of the study was to determine the prevalence of adherence to ART and identify factors associated with non-adherence to ART among HIV infected adults registered in a private sector setting in Mon State, Myanmar. Methods This cross-sectional study was conducted with adults living with HIV receiving ART at an HIV outpatient clinic between April and May 2016. A total of three hundred People Living with HIV(PLHIV were interviewed using a pretested and structured questionnaire. The 30 days Visual Analog Scale (VAS adherence instrument was used to assess the level of adherence. Multivariable logistic regression analysis was used to determine factors associated with non-adherence to ART. Results Among 300 patients (male 37.7% and female 62.3%, with a mean age of 41.3 years, standard deviation 8.7, 84% reported ≥95% adherence to ART in the past month. Among 16% of those reporting non-adherence, major reasons for skipping the medication were being busy (23%, being away from home (17.7% and being forgetful (12.3%. In multivariable logistic rgeression, low behavioural skills on ART adherence (OR = 0.31, 95% CI: 0.10-0.94, tobacco use (OR = 3.22, 95% CI:1.28-8.12, having disclosed their HIV status (OR = 0.07, 95% CI: 0.01-0.69, having a partner who was not on ART (OR = 4.25, 95% CI: 1.70-10.64 and among men, having erectile dysfunction (OR = 15.14, 95% CI: 1.41-162.66 were significant associated with ART non-adherence. Conclusion Non-adherence to ART was associated with individual moderating factors and behavioral skills. Priority measures such as addressing risk behaviour and behavioural change communication tailored to individual patients’ lifestyles requires comprehensive

Non-adherence to anti-retroviral therapy among HIV infected adults in Mon State of Myanmar.

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Aye, Win Lei; Puckpinyo, Apa; Peltzer, Karl

2017-05-05

The provision of Anti-Retroviral Therapy (ART) was started in Myanmar in 2005 in collaboration with the National AIDS Program and the private sector. Successful clinical management of HIV-infected patients is subject to optimal adherence. The aim of the study was to determine the prevalence of adherence to ART and identify factors associated with non-adherence to ART among HIV infected adults registered in a private sector setting in Mon State, Myanmar. This cross-sectional study was conducted with adults living with HIV receiving ART at an HIV outpatient clinic between April and May 2016. A total of three hundred People Living with HIV(PLHIV) were interviewed using a pretested and structured questionnaire. The 30 days Visual Analog Scale (VAS) adherence instrument was used to assess the level of adherence. Multivariable logistic regression analysis was used to determine factors associated with non-adherence to ART. Among 300 patients (male 37.7% and female 62.3%, with a mean age of 41.3 years, standard deviation 8.7), 84% reported ≥95% adherence to ART in the past month. Among 16% of those reporting non-adherence, major reasons for skipping the medication were being busy (23%), being away from home (17.7%) and being forgetful (12.3%). In multivariable logistic rgeression, low behavioural skills on ART adherence (OR = 0.31, 95% CI: 0.10-0.94), tobacco use (OR = 3.22, 95% CI:1.28-8.12), having disclosed their HIV status (OR = 0.07, 95% CI: 0.01-0.69), having a partner who was not on ART (OR = 4.25, 95% CI: 1.70-10.64) and among men, having erectile dysfunction (OR = 15.14, 95% CI: 1.41-162.66) were significant associated with ART non-adherence. Non-adherence to ART was associated with individual moderating factors and behavioral skills. Priority measures such as addressing risk behaviour and behavioural change communication tailored to individual patients' lifestyles requires comprehensive interventions to improve adherence.

Therapeutic genes for anti-HIV/AIDS gene therapy.

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Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

2013-01-01

The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

Thyroid function in HIV patients treated with highly active antiretroviral therapy (HAART)

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Madeddu, Gr.; Calia, G.M.; Lovigu, C.; Mannazzu, M.; Mura, M.S.; Spanu, A.; Solinas, P.; Falchi, A.; Madeddu, G.

2002-01-01

Aim: Altered thyroid function parameters have been reported in HIV patients also during therapy. We further investigated whether thyroid disorders occur in HIV patients both naive or on HAART. Materials and Methods: We enrolled 168 HIV patients aged 20 to 62 yrs, 110M and 58F: 95 patients (G1) were on HAART including protease inhibitors-PI (36.89±13.0 mths); 58 (G2) were on HAART (Nevirapine or Efavirenz) without PI (13.22±8.68 mths) and previously submitted to other HAART regimens (28.10±12.3 mths); 15 (G3) were naive. In all patients and in 44 age-sex matched normal subjects (C) we measured in serum by IRMA, FT3 and FT4 (pg/ml), TSH (μU/ml), antithyroid peroxidase (TPO) and hTG (U/ml) antibodies (Ab). Results: Thyroid function test abnormalities were found in 18/153 patients treated with HAART (11.7%), 9 G1 and 9 G2 patients, while the tests were normal in naive cases. Both FT3 and FT4 were above normal range and TSH suppressed in one G1 patient with clinical signs of hyperthyroidism; FT4 was low and TSH elevated in 2 G2 cases with slight clinical signs of hypothyroidism. Moreover, TSH values >3.5 μU/ml and normal FT3 and FT4 levels were ascertained in 7 further cases as probable subclinical hypothyroidism. Only FT4 was low in 3 further cases and FT3 high in 5 others, all asymptomatic. hTG-Ab were present in 2 subclinical hypothyroidism patients and in 3 further cases with normal thyroid tests. Mean TSH levels were higher but not significantly in G1 than in G2; both were higher than in G3 and C. FT4 levels were significantly lower in G1 (12.294±2.938; p<0.002), G2 (11.091±2.453; p<0.00002) and G3 (10.186±2.537; p<0.00004) than in C (13.734±2.205). FT4 was significantly lower in G2 (p<0.006) and G3 ( p<0.01) than in G1; there was no difference between G2 and G3. FT3 was higher in G1 (3.711±0.559) and G2 (3.60±0.581) than in G3 (3.42±0.549) and C (3.452±0.343); the difference was significant (p<0.01) only between G1 and C. Neither FT3, FT4 nor TSH

Anemia and risk factors in HAART naïve and HAART experienced HIV positive persons in south west Ethiopia: a comparative study.

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Lealem Gedefaw

Full Text Available BACKGROUND: Human immunodeficiency virus (HIV infection and its treatment cause a range of hematological abnormalities. Anemia is one of the commonly observed hematologic manifestations in HIV positive persons and it has multifactorial origin. OBJECTIVE: We aimed to determine the prevalence and risk factors of anemia in highly active antiretroviral therapy (HAART naïve and HAART experienced HIV positive persons. METHODS: A facility-based comparative cross sectional study was conducted in Jimma University Specialized Hospital from February 1 to March 30, 2012. A total of 234 HIV positive persons, 117 HAART naïve and 117 HAART experienced, were enrolled in this study. Blood and stool specimens were collected from each participant. Blood specimens were examined for complete blood count, CD4 count and blood film for malaria hemoparasite; whereas stool specimens were checked for ova of intestinal parasites. Socio-demographic characteristics and clinical data of the participants were collected using pre-tested questionnaire. Statistical analysis of the data (Chi-square, student's t-test, logistic regression was done using SPSS V-16. RESULTS: The overall prevalence of anemia was 23.1%. The prevalence of anemia in HAART naïve and HAART experienced persons was 29.9% and 16.2%, respectively (P = 0.014. Presence of opportunistic infections (P = 0.004, 95% CI = 1.69-15.46, CD4 count <200 cells/µl (P = 0.001, 95% CI = 2.57-36.89 and rural residence (P = 0.03, 95% CI = 1.12-10.39 were found to be predictors of anemia for HAART naïve participants. On the other hand, HAART regimen (ZDV/3TC/NVP (P = 0.019, 95% CI = 0.01-1.24 and the duration of HAART (P = 0.007, 95% CI = 0.003-0.40.24 were found to be predictors of anemia for HAART experienced groups. CONCLUSION: The prevalence of anemia in HAART naïve persons was higher than HAART experienced persons. Risk factors for anemia in HAART naïve and HAART experienced HIV positive persons were different. Hence

Alteraciones metabólicas con terapia antirretroviral altamente efectiva en niños positivos para VIH, Cali, Colombia Metabolic alterations with anti-retroviral highly effective therapy in positive children for VIH, Cali, Colombia

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Pío López

2009-12-01

metabolic alterations in children with HIV and under highly effective anti-retroviral treatment (HAART. Methodology: a first descriptive phase of lipid levels and glucemia was carried out in a cohort of HIV positive children. In a paediatric hospital, children >1 month and <16 years old under HAART were recruited from June, 2003 to June, 2005. The results were compared to population values. During the second phase, bone density was studied in these children using DEXA and anthropometric values and compared to healthy control subjects. Results: thirty eight positive children were included. 59.5% of the children were classified as having dyslipidemia. Upon comparison to the reference population, the HIV(+ group showed larger hypertrigliceridemia prevalence and abnormally low cHDL. Taking into account age variations, total colesterol values and cLDL showed increase in the group that received PI against those that did not. The difference of the BMD Z-Score among the groups was 0,56 (CI95%: 0.1, 1.0, the HIV(+ group having a smaller Z-Score. The bone mass density Z-Score showed a decline according exposition time, which was not evident in the control group. Conclusions: alterations in lipids similar to those described in the seropositive adult were found. The group with PI showed cholesterol alterations that changed according to age. Progressive bone density loss according to exposition time was found regardless of age. It is considered that this relationship could have multifactorial origin, including infection and treatment effects

HAART in hand: The change in Kaposi's sarcoma presentation in ...

African Journals Online (AJOL)

Background. HIV/AIDS-related Kaposi's sarcoma (HIV-KS) is a public health problem in South Africa (SA). It is AIDS defining. There have been no studies evaluating its prevalence since the national roll-out of highly active antiretroviral therapy (HAART). Objective. To evaluate the effect of HAART on the disease profile of ...

A STUDY OF ANTIRETROVIRAL THERAPY OUTCOMES IN A TERTIARY CARE CENTER IN THANJAVUR MEDICAL COLLEGE HOSPITAL, SOUTHERN INDIA

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Kannan V. P

2017-05-01

Full Text Available BACKGROUND The number of people infected with the Human Immunodeficiency Virus (HIV worldwide was estimated to be 33.2 million at the end of 2007. The introduction of Anti-Retroviral Therapy (ART has significantly reduced morbidity and mortality in HIVinfected patients in various developed and developing countries. However, the outcome of ART in India’s National ART Programme has not been reported in detail. The aim of the study is to- 1. Evaluate the immunological response of HIV infected adults starting Highly Active Antiretroviral Therapy (HAART. 2. Evaluate the clinical response of highly active antiretroviral therapy in HIV infected adults. 3. Assess the functional status improvement following highly active antiretroviral therapy. MATERIALS AND METHODS To evaluate the effectiveness of the National ART Programme at Thanjavur Medical College Hospital, we undertook a prospective observational study involving ART naive patients who were started on ART between May 2015 and October 2016. ART was offered to these patients in accordance with NACO guidelines. The regimen consisted of two nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitor. The available drugs included efavirenz, lamivudine, nevirapine and zidovudine. The CD4+ lymphocyte (CD4 count (cells/µL was estimated at baseline and at six months intervals during follow-up. Prophylaxis and treatment of opportunistic infections were in accordance with NACO guidelines. Anti-tuberculosis treatment was administered according to the Revised National Tuberculosis Control Programme guidelines. RESULTS Among 203 patients started on ART in this study, 3 died after completing 6 months of therapy and 17 died within 6 months of therapy. Out of the remaining 183 patients, 104 were males and 79 were females. The predominant route of HIV transmission is through unsafe sexual practice, which accounts for 84% of cases. Incidence of HIV is less common in literate

The first ten years: achievements and challenges of the Brazilian program of universal access to HIV/AIDS comprehensive management and care, 1996-2006.

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Hacker, Mariana A; Kaida, Angela; Hogg, Robert S; Bastos, Francisco I

2007-01-01

A review was carried out of papers published between 1996 and 2006, documenting the introduction of highly active anti-retroviral therapy (HAART) in Brazil. Papers indexed in the MEDLINE and SciELO databases were retrieved using different combinations of keywords related to the management and care of AIDS in the post-HAART era: opportunistic diseases and co-infections, adherence to therapy, survival in the pre- and post-HAART eras, adverse events and side-effects, emergence and possible transmission of resistant viral strains, metabolic and cardiovascular disorders, and issues related to access to care and equity. The review documents the dramatic changes in HIV/AIDS disease progression in the post-HAART era, including an increase in survival and quality of life and a pronounced decrease in the episodes of opportunistic diseases. Notwithstanding such major achievements, new challenges have emerged, including slow evolving co-infections (such as hepatitis C, metabolic and cardiovascular disorders), the emergence of viral resistance, with consequences at the individual level (virological failure) and the community level (primary/secondary resistance at the population level), and impacts on the cost of new therapeutic regimens.

Financial and economic costs of scaling up the provision of HAART ...

African Journals Online (AJOL)

Objectives: To provide new information on the financial and economic costs of providing highly active antiretroviral therapy (HAART) to health care workers in public-sector hospital settings in KwaZulu-Natal. Design: An Excel model was used to estimate the cost of providing HAART to health care workers at two ...

Hospitalization due to Adverse Drug Reactions and Drug Interactions before and after HAART

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Michelle M Foisy

2000-01-01

Full Text Available OBJECTIVE: To characterize and compare the rates of adverse drug reactions (ADRs and interactions on admission in two, one-year periods: pre-highly active antiretroviral therapy (HAART (phase 1 and post-HAART (phase 2.

Smart nanoparticles as targeting platforms for HIV infections

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Adhikary, Rishi Rajat; More, Prachi; Banerjee, Rinti

2015-04-01

While Human Immunodeficiency Virus (HIV) infections are reducing in incidence with the advent of Highly Active Anti-retroviral Therapy (HAART), there remain a number of challenges including the existence of reservoirs, drug resistance and anatomical barriers to antiretroviral therapy. To overcome these, smart nanoparticles with stimuli responsive release are proposed for delivery of anti-retroviral agents. The paper highlights the strategic similarities between the design of smart antiretroviral nanocarriers and those optimized for cancer chemotherapy. This includes the development of nanoparticles capable of passive and active targeting as well as those that are responsive to various internal and external triggers. For antiretroviral therapy, the relevant triggers for stimuli responsive release of drugs include semen, enzymes, endosomal escape, temperature and magnetic field. Deriving from the experience of cancer chemotherapy, additional potential triggers are light and ultrasound which remain hitherto unexplored in HIV therapy. In addition, the roles of nanomicrobicides (nanogels) and virus mimetic nanoparticles are discussed from the point of view of prevention of HIV transmission. The challenges associated with translation of smart nanoparticles for HIV infections to realize the Millennium Development Goal of combating HIV infections are discussed.

Examining the relationship between psychological distress and adherence to anti-retroviral therapy among Ugandan adolescents living with HIV.

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Mutumba, Massy; Musiime, Victor; Lepkwoski, James M; Harper, Gary W; Snow, Rachel C; Resnicow, Ken; Bauermeister, Jose A

2016-07-01

Psychological distress is common among adolescents living with HIV (ALHIV) worldwide, and has been associated with non-adherence to anti-retroviral therapy (ART), leading to poor virologic suppression, drug resistance, and increased risk for AIDS morbidity and mortality. However, only a few studies have explored the relationship between psychological distress and ART adherence among adolescents in sub-Saharan Africa. The paper examines the relationship between psychological distress and ART adherence, and effect of psychosocial resources on ART adherence. We conducted a cross-sectional survey of 464 ALHIV (aged 12-19; 53% female) seeking HIV care at a large HIV treatment center in Kampala, Uganda. ALHIV were recruited during routine clinic visits. Three self-reported binary adherence measures were utilized: missed pills in the past three days, non-adherence to the prescribed medical regimen, and self-rated adherence assessed using a visual analog scale. Psychological distress was measured as a continuous variable, and computed as the mean score on a locally developed and validated 25-item symptom checklist for Ugandan ALHIV. Psychosocial resources included spirituality, religiosity, optimism, social support, and coping strategies. After adjusting for respondents' socio-demographic characteristics and psychosocial resources, a unit increase in psychological distress was associated with increased odds of missing pills in past 3 days (Odds Ratio(OR) = 1.75; Confidence Interval (CI): 1.04-2.95), not following the prescribed regimen (OR = 1.63; CI: 1.08-2.46), and lower self-rated adherence (OR = 1.79; CI: 1.19-2.69). Psychosocial resources were associated with lower odds for non-adherence on all three self-report measures. There is a need to strengthen the psychosocial aspects of adolescent HIV care by developing interventions to identify and prevent psychological distress among Ugandan ALHIV.

Suplementação de N-acetilcisteína em pacientes infectados pelo HIV submetidos ao primeiro tratamento anti-retroviral: Avaliação do efeito sobre a carga viral, TNF-α, IL-6, IL-8, β2-microglobulina, IgA, IgG e IgM, haptoglobina e α1-glicoproteína ácida N-acetylcysteine supplementation of HIV-infected patients under the first anti-retroviral treatment: Evaluation of the effect on viral load, TNF-α, IL-6, IL-8, β2-microglobulin, IgA, IgG, IgM, haptoglobin and α1-acid glycoprotein

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Aricio Treitinger

2002-03-01

alterations are characterized by elevated levels of tumor necrosis factor alpha (TNF-α, interleukin 8 (IL-8, β2-microglobulin, IgA, IgG, IgM, haptoglobin and a1-acid glycoprotein. The goal of this double blind placebo-controlled study was to evaluate the effect of N-acetylcysteine supplementation on virological, immunological and inflammatory markers in 24 HIVinfected individuals who were taking their first anti-retroviral therapy. Eleven individuals were treated with anti-retroviral therapy plus placebo supplementation and thirteen were treated with anti-retroviral therapy plus 600 mg/day of Nacetylcysteine. The levels of the studied markers were evaluated at the day before and after 60, 120 and 180 days of treatment. In both groups a significant decrease in serum levels of TNF-α (p=0.0001, IL-6 (p>0.05, IL-8 (p=0.0001, b2 microglobulin (p=0.0005, IgA (p=0.007, IgG (p=0.001, IgM (p=0.0001, haptoglobin (p=0.0001 e α1-acid glycoprotein (p=0.012 was found due to anti-retroviral therapy. N-acetylcysteine supplementation had no additive or synergistic effects on the studied parameters. In conclusion, N-acetylcysteine had no additional beneficial effects, at least at the dose used in this study, on the treatment of HIV-infected patients under anti-retroviral therapy.

Premature and accelerated aging: HIV or HAART?

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Smith, R.L.; de Boer, R.; Brul, S.; Budovskaya, Y.; van der Spek, H.

2013-01-01

Highly active antiretroviral therapy (HAART) has significantly increased life expectancy of the human immunodeficiency virus (HIV)-positive population. Nevertheless, the average lifespan of HIV-patients remains shorter compared to uninfected individuals. Immunosenescence, a current explanation for

Cross- and Co-Packaging of Retroviral RNAs and Their Consequences

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Lizna M. Ali

2016-10-01

Full Text Available Retroviruses belong to the family Retroviridae and are ribonucleoprotein (RNP particles that contain a dimeric RNA genome. Retroviral particle assembly is a complex process, and how the virus is able to recognize and specifically capture the genomic RNA (gRNA among millions of other cellular and spliced retroviral RNAs has been the subject of extensive investigation over the last two decades. The specificity towards RNA packaging requires higher order interactions of the retroviral gRNA with the structural Gag proteins. Moreover, several retroviruses have been shown to have the ability to cross-/co-package gRNA from other retroviruses, despite little sequence homology. This review will compare the determinants of gRNA encapsidation among different retroviruses, followed by an examination of our current understanding of the interaction between diverse viral genomes and heterologous proteins, leading to their cross-/co-packaging. Retroviruses are well-known serious animal and human pathogens, and such a cross-/co-packaging phenomenon could result in the generation of novel viral variants with unknown pathogenic potential. At the same time, however, an enhanced understanding of the molecular mechanisms involved in these specific interactions makes retroviruses an attractive target for anti-viral drugs, vaccines, and vectors for human gene therapy.

Fairness and equity in the provision of anti-retroviral therapy: some reflections from Lesotho.

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Armstrong, Russell

2010-12-01

The number of people in immediate need of anti-retroviral treatment (ART) in the southern African region continues to significantly exceed the capacity of health systems there to provide it. Approaches to this complex rationing dilemma have evolved in different directions. The ethical concepts of fairness and equity have been suggested as a basis to guide the development of approaches to select patients for ART. This article reports the results of a case study on patient selection at a rural ART clinic in Lesotho. The purpose of the study was to examine whether or not such concepts had relevance or operative value for a treatment team providing ART in rural Lesotho. The study found that while concepts of fairness and equity were relevant to the work of the treatment team, patient selection practices did not necessarily reflect what these concepts entail. The idea of fairness as a structured, formalized selection process did not figure in the approach to ART provision at the site. A less formal, 'first-come-first-served' approach was adopted. While there was knowledge among some team members that social, economic or geographic conditions inhibit individuals and groups from gaining access to ART and that this was inequitable, it was felt that there was little they could do to try to mediate the impact of these conditions. The study's findings pose importance questions about the approach to ART programming in resource constrained settings. The findings also question the relevance of trying to achieve fairness and equity when the gap between need for care and capacity to provide it remains so large. © 2009 Blackwell Publishing Ltd.

Adherence to anti-retroviral therapy & factors associated with it: A community based cross-sectional study from West Bengal, India

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Sobha Pahari

2015-01-01

Full Text Available Background & objectives: Failure to adhere to anti-retroviral therapy (ART can lead to a range of unfavourable consequences impacting upon people living with HIV (PLH and society. It is, therefore, paramount that ART adherence is measured in a reliable manner and factors associated with adherence are identified. Lack of such data from West Bengal necessitated undertaking the current study. Methods: Participants were included during August-October, 2011 from three Drop-In-Centres (DICs from the three districts of West Bengal, India. ART-adherence was calculated by using formula based on pill-count and records collected from ART-card in possession of each of the 128 consenting adult PLH. Information on self-reported adherence, socio-demography, and adherence influencing issues was also collected through interviewer-administered questionnaire. Results: Of the 128 PLH, 99 (77% and 93 (73% PLH had ≥90 per cent and ≥95 per cent adherence, respectively to ART. Conversely, subjective reporting captured much higher proportion of PLH as ′well adherent′; a finding having implications for ongoing ART programme. Factors, independently associated with poor adherence (<90%, were ′7 th to 12 th month period of ART intake′ (adjusted OR=9.5; 90% CI 1.9 - 47.3; p0 =0.02 and ′non-disclosure of HIV status to family members′ (adjusted OR=4; 90% CI 1.3 - 13; P=0.05. Results at 95 per cent adherence cut-off were similar. Interpretation & conclusions: Enabling environment, which would encourage people to disclose their HIV status and in turn seek adherence partners from families and beyond and ongoing adherence-counselling appear to be important issues in the programme. Relevance of these study findings in wider context is conceivable.

Terapia hipolipemiante em situações especiais: síndrome de imunodeficiência adquirida Hypolipidemic therapy under special conditions: acquired immune deficiency syndrome

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Pai Ching Yu

2005-10-01

Full Text Available Dislipidemias podem ser observadas precocemente entre pacientes com AIDS. Frequentemente, estas anormalidades lipídicas incluem HDL baixo e moderado aumento dos triglicérides sanguíneos. A terapia anti-retroviral combinada (HAART pode agravar a dislipidemia nestes pacientes, com importante aumento nos triglicérides e no LDL. Vários mecanismos são propostos para explicar a dislipidemia mista observada nestes indivíduos, incluindo diferentes etapas do metabolismo lipídico. A importância do tratamento desses distúrbios lipídicos tem se tornado evidente com o aumento da expectativa de vida e os relatos de complicações cardiovasculares nestes pacientes. Existe um estado de resistência à insulina nos pacientes com AIDS em tratamento com HAART,que apresentam lipodistrofia, hipertrigliceridemia e baixos níveis de HDL. Drogas retro-antivirais são metabolizadas pelo CYP P450 3A4 e interações com algumas estatinas, especialmente com sinvastatina podem ocorrer. O tratamento com agentes hipolipemiantes deve ser baseado no perfil lipídico e no risco de coronariopatia. Para hipertrigliceridemias, fibratos (principalmente fenofibrato ou bezafibrato devem ser as drogas de escolha, bem como as estatinas (principalmente pravastatina. Terapia combinada usando estatinas mais fibratos é recomendada para dislipidemias mistas graves e sempre sob rigoroso monitoramento de efeitos adversos.Lipid alterations can be observed early among patients with AIDS disease. Commonly, these lipid abnormalities include low HDL-C and modest increase in triglyceride plasma levels. Highly Active Anti-Retroviral Therapy (HAART in these patients may aggravate the dyslipidemia, with notable increases in triglycerides as well as in LDL-C. There are several mechanisms proposed to explain the mixed hyperlipidemia observed in these subjects, including different steps in lipid metabolism. The importance of the treatment of dyslipidemia became evident with the increased life

WHO 2009 GUIDELINES FOR ANTI-RETROVIRAL THERAPHY: ITS IMPLICATION FOR PRIMARY CARE PHYSICIAN

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KOH KC

2010-01-01

Full Text Available -The HIV epidemic in Malaysia is slowing down but has now spread to spouses and sexual partners of traditional at risk populations, via heterosexual transmission. -The WHO 2009 guideline advocates starting HAART at CD4 level of 350 cells/mm3, marking a significant departure from starting at CD4 level of 200 cells/mm3 previously. -The WHO 2009 guideline recommended replacing stavudine with either zidovudine or tenofovir as part of the first line HAART regimen due to the former’s adverse effects. -Early detection of HIV infection and earlier initiation of HAART translates into better quality of life and lower risk of Tuberculosis co-infection. -Earlier detection of HIV infection requires picking up on subtle signs of the infection as well as employing a host of available diagnostic tests in cases where HIV infection is strongly suspected. -HIV test should be offered as a part of a routine health check screening. This facilitates early detection of HIV infection and early referral to the hospital for further management. -Collaboration and communications with non-governmental organizations involved in care of HIV infected people can be a good mean of providing support and counselling to newly diagnosed HIV infected individuals. -Asymptomatic undiagnosed HIV infected patients may pose a risk for disease transmission to health care workers in the primary care setting. Steps must be taken to minimize the risk of transmission and easy access to post-exposure prophylaxis. -The primary care physician should be well versed with the many possible drug interactions between HAART and other commonly used medications for other illnesses in order to avoid potentially fatal adverse reactions or treatment failure in patients taking HAART.

A decade of HAART in Latin America: Long term outcomes among the first wave of HIV patients to receive combination therapy.

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Wolff, Marcelo J; Giganti, Mark J; Cortes, Claudia P; Cahn, Pedro; Grinsztejn, Beatriz; Pape, Jean W; Padgett, Denis; Sierra-Madero, Juan; Gotuzzo, Eduardo; Duda, Stephany N; McGowan, Catherine C; Shepherd, Bryan E

2017-01-01

In Latin America, the first wave of HIV-infected patients initiated highly active antiretroviral therapy (HAART) 10 or more years ago. Characterizing their treatment experience and corresponding outcomes across a decade of HAART may yield insights relevant to the ongoing care of such patients and those initiating HAART more recently in similar clinical settings. This retrospective study included adults initiating HAART before 2004 at 8 sites in Argentina, Brazil, Chile, Haiti, Honduras, and Mexico. Patient status (in care, dead, or lost to follow-up [LTFU]) was assessed at 6-month intervals for 10 years, along with CD4 count and HIV-1 viral load (VL) for patients in care. 4,975 patients (66% male) started HAART prior to 2004; 45% were not antiretroviral-naïve. At 1, 5, and 10 years, rates of mortality were 4.2%, 9.0%, and 13.6% respectively. LTFU rates for the same periods were 2.4%, 10.9%, and 24.2%. Among patients remaining in care at 10 years, 84.4% were estimated to have VL≤400 copies/mL (Haiti excluded) and median baseline CD4 increased from 158 to 525 cells/mm3. Only 11.4% of all patients remained on their first regimen, 12.6% were on their second, 11.5% were on their third, and 23.0% were on their fourth or subsequent regimen. Outcomes were generally better for patients who were not antiretroviral-naïve, except for viral suppression. Heterogeneity among sites was substantial. Despite advanced disease and predominant use of older antiretrovirals, a large percentage of early HAART initiators in this Latin American cohort were alive and in care with sustained virologic suppression and progressive immune recovery after 10 years.

A decade of HAART in Latin America: Long term outcomes among the first wave of HIV patients to receive combination therapy

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Wolff, Marcelo J.; Giganti, Mark J.; Cortes, Claudia P.; Cahn, Pedro; Grinsztejn, Beatriz; Pape, Jean W.; Padgett, Denis; Sierra-Madero, Juan; Gotuzzo, Eduardo; Duda, Stephany N.; McGowan, Catherine C.; Shepherd, Bryan E.

2017-01-01

Background In Latin America, the first wave of HIV-infected patients initiated highly active antiretroviral therapy (HAART) 10 or more years ago. Characterizing their treatment experience and corresponding outcomes across a decade of HAART may yield insights relevant to the ongoing care of such patients and those initiating HAART more recently in similar clinical settings. Methods This retrospective study included adults initiating HAART before 2004 at 8 sites in Argentina, Brazil, Chile, Haiti, Honduras, and Mexico. Patient status (in care, dead, or lost to follow-up [LTFU]) was assessed at 6-month intervals for 10 years, along with CD4 count and HIV-1 viral load (VL) for patients in care. Results 4,975 patients (66% male) started HAART prior to 2004; 45% were not antiretroviral-naïve. At 1, 5, and 10 years, rates of mortality were 4.2%, 9.0%, and 13.6% respectively. LTFU rates for the same periods were 2.4%, 10.9%, and 24.2%. Among patients remaining in care at 10 years, 84.4% were estimated to have VL≤400 copies/mL (Haiti excluded) and median baseline CD4 increased from 158 to 525 cells/mm3. Only 11.4% of all patients remained on their first regimen, 12.6% were on their second, 11.5% were on their third, and 23.0% were on their fourth or subsequent regimen. Outcomes were generally better for patients who were not antiretroviral-naïve, except for viral suppression. Heterogeneity among sites was substantial. Conclusions Despite advanced disease and predominant use of older antiretrovirals, a large percentage of early HAART initiators in this Latin American cohort were alive and in care with sustained virologic suppression and progressive immune recovery after 10 years. PMID:28651014

The First Synthesis and Anti-retroviral Activity of 5',5'-Difluoro-3'-Hydroxy-Apiosyl Nucleoside Cyclomonophosphonic Acid Analogs

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Kim, Seyeon; Hong, Joon Hee [Chosun University, Gwangju (Korea, Republic of)

2016-04-15

The first synthesis of novel 5',5'-difluoro-30-hydroxy apiose nucleoside cyclomonophosphonic acid analogs was performed as potent anti-retroviral agents. Phosphonation was performed by direct displacement of a triflate intermediate with diethyl(lithiodifluoromethyl) phosphonate to give the corresponding(α, α-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside cyclomonophosphonic acid analogs. The synthesized nucleoside analogs were subjected to anti-viral screening against the human immunodeficiency virus-1 (HIV-1). Cytosine analogs show significant anti-HIV activity.

A qualitative assessment of decisions affecting contraceptive utilization and fertility intentions among HIV-positive women in Soweto, South Africa.

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Laher, Fatima; Todd, Catherine S; Stibich, Mark A; Phofa, Rebecca; Behane, Xoliswa; Mohapi, Lerato; Gray, Glenda

2009-06-01

The HIV epidemic in sub-Saharan Africa disproportionately affects women of reproductive age. The increasing provision of Highly Active Anti-Retroviral Therapy (HAART) with improved prognosis and maternal-fetal outcomes calls for an understanding of fertility planning for HIV-positive women. We describe the effect of HIV and HAART on pregnancy desires and contraceptive use among HIV-positive women in Soweto, South Africa. Focus group discussions and in-depth interviews were conducted with 42 HIV-positive women of reproductive age. Analysis was performed using ATLAS-ti (ATLAS-ti Center, Berlin). Emergent themes were impact of HIV diagnosis on pregnancy intentions; factors affecting contraceptive uptake including real and normative side effects, body image, and perceived vaginal wetness; and the mitigating influence of partnership on both pregnancy intentions and contraceptive use. Routine counseling about pregnancy desires and contraception should be offered to HIV-positive women.

Electronic medication monitoring-informed counseling to improve adherence to combination anti-retroviral therapy and virologic treatment outcomes: a meta-analysis.

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Langebeek, Nienke; Nieuwkerk, Pythia

2015-01-01

Adherence to combination anti-retroviral therapy for HIV infection is a primary determinant of treatment success, but is often suboptimal. Previous studies have suggested that electronic medication monitoring-informed counseling is among the most effective adherence intervention components. Our objective was to review available evidence about the effectiveness of monitoring-informed counseling and to aggregate findings into quantitative estimates of the effect of such intervention on medication adherence and virologic treatment outcomes. We searched PubMed for papers reporting on randomized controlled trials comparing intervention groups receiving monitoring-informed counseling as one of the intervention components versus control groups not receiving such counseling for their effect on medication adherence and viral load concentrations. The standardized mean difference (SMD) in adherence and the odds ratio (OR) of undetectable HIV RNA in intervention versus control groups were the common effect sizes. Random-effect models with inverse variance weights were used to aggregate findings into pooled effect estimates with 95% confidence limits (CI). A total of 13 studies were included. Adherence was significantly higher in intervention groups than in control groups (SMD 0.51, 95% CI 0.31-0.71). Patients in intervention groups were significantly more likely to have undetectable HIV RNA concentrations than patients in control groups (OR 1.35, 95% CI 1.12-1.63). However, in studies in which monitoring-informed counseling was the only intervention component, the difference in adherence and virologic response between intervention and control groups was not statistically significant. Electronic monitoring-informed counseling improved adherence and virologic response compared with control groups not receiving such counseling in studies in which it was one out of multiple intervention components, but not in studies where it was the only intervention component.

Evaluation of patterns of liver toxicity in patients on antiretroviral and anti-tuberculosis drugs: a prospective four arm observational study in ethiopian patients.

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Getnet Yimer

Full Text Available OBJECTIVES: To evaluate the incidence, type, severity and predictors of antiretroviral and/or anti-tuberculosis drugs induced liver injury (DILI. METHODS: A total of 1,060 treatment naive patients were prospectively enrolled into four treatment groups: HIV patients receiving efavirenz based HAART alone (Arm-1; TB-HIV co-infected patients with CD4≤200 cells/μL, receiving concomitant rifampicin based anti-TB and efavirenz based HAART (Arm-2; TB-HIV co-infected patients with CD4>200 cells/μL, receiving anti-TB alone (Arm-3; TB patients taking rifampicin based anti-TB alone (Arm-4. Liver enzyme levels were monitored at baseline, 1st, 2nd, 4th, 8th, 12th and 24th weeks during treatment. CD4 and HIV viral load was measured at baseline, 24th and 48th weeks. Data were analyzed using multivariate Cox Proportional Hazards Model. RESULTS: A total of 159 patients (15% developed DILI with severity grades 1, 2, 3 and 4 of 53.5%, 32.7%, 11.3% and 2.5% respectively. The incidence of cholestatic, hepatocellular or mixed pattern was 61%, 15% and 24%, respectively. Incidence of DILI was highest in Arm-2 (24.2%>Arm-3 (10.8%>Arm-1 (8.8%>Arm-4 (2.9%. Concomitant anti-TB-HIV therapy increased the risk of DILI by 10-fold than anti-TB alone (p<0.0001. HIV co-infection increased the risk of anti-TB DILI by 4-fold (p = 0.004. HAART associated DILI was 3-fold higher than anti-TB alone, (p = 0.02. HAART was associated with cholestatic and grade 1 DILI whereas anti-TB therapy was associated with hepatocellular and grade ≥ 2. Treatment type, lower CD4, platelet, hemoglobin, higher serum AST and direct bilirubin levels at baseline were significant DILI predictors. There was no effect of DILI on immunologic recovery or virologic suppression rate of HAART. CONCLUSION: HAART associated DILI is mainly cholestatic and mild whereas hepatocellular or mixed pattern with high severity grade is more common in anti-tuberculosis DILI. TB-HIV co-infection, disease severity

A phase I/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy (HAART) in HIV-positive patients with cancer: AIDS Malignancy Consortium Trial AMC 061

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Rudek, Michelle A; Moore, Page C.; Mitsuyasu, Ronald T.; Dezube, Bruce J.; Aboulafia, David; Gerecitano, John; Sullivan, Ryan; Cianfrocca, Mary E.; Henry, David H.; Ratner, Lee; Haigentz, Missak; Dowlati, Afshin; Little, Richard F.; Ivy, S. Percy; Deeken, John F.

2014-01-01

Background Treatment of non-AIDS defining cancers (NADCs) may be complicated by drug interactions between highly active antiretroviral therapy (HAART) and chemotherapy. This trial is the first by the AIDS Malignancy Consortium assessing targeted therapies and HAART in HIV+ cancer patients (ClinicalTrials.gov NCT00890747). Methods Patients were stratified into two arms based on whether they were taking ritonavir, a potent CYP3A4 inhibitor, in a modified phase I study of sunitinib. Patients in arm 1 (non-ritonavir HAART) received standard sunitinib dosing (50mg/day). Arm 2 (ritonavir-based HAART) used a phase I, 3+3 dose escalation design (from 25 to 50mg/day). Cycles were with four weeks on treatment followed by a two week break (6 weeks total). Pharmacokinetics of sunitinib and its active metabolite (N-desethyl sunitinib) were assessed. Results Nineteen patients were enrolled and evaluable. Patients on Arm 1 tolerated treatment with one observed dose limiting toxicity (DLT). In Arm 2, a DLT was experienced at 37.5mg, and an additional 3 of 5 patients experienced grade 3 neutropenia, an uncommon toxicity of sunitinib. No patient had a response, but 10 had stable disease, including 8 with prolonged disease stability. Efavirenz, a potent inducer of CYP3A4, resulted in increased exposure of N-desethyl sunitinib, whereas ritonavir caused decreased exposure of the metabolite. Hand-foot syndrome was associated with higher steady-state trough concentrations of sunitinib. Conclusions Patients on non-ritonavir based HAART regimens tolerated standard dosing of sunitinib. Patients on ritonavir-based therapy treated with 37.5mg/day experienced higher toxicities. Dose reduction of sunitinib to 37.5mg may be warranted in patients on ritonavir. PMID:24474568

Novel Nanotechnology Strategies for the Treatment and Prevention of HIV Infection

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Tan, Jian Jun; Sun, Xiao Hui; Ma, Xue Ting; Guan, Jian Qing; Wang, Cun Xin

2013-09-01

It is a hard work to develop an hightly effective cure and prevention of HIV/AIDS. The widespread used of some therapy approaches such as highly active anti retroviral therapy (HAART) has improved life quality and span of infected individuals. However, some limitations of these approaches prevent them achieving further advancement. Recent research on drug delivery approaches indicates that engineered nanosystems may bring positive effect on the improvement of current antiretroviral therapy. Furthermore, the basic researches of nanotechnology- based systems which prevent HIV transmission have been started. Therefore, nanotechnology may become a potential approach in the field of HIV/AIDS treatment and prevention. This chapter reviews the latest advancement in the field of nanotechnology-based systems which improve the fields of HIV/AIDS treatment and prevention.

Metropolitan social environments and pre-HAART/HAART era changes in mortality rates (per 10,000 adult residents among injection drug users living with AIDS.

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Samuel R Friedman

Full Text Available Among the largest US metropolitan areas, trends in mortality rates for injection drug users (IDUs with AIDS vary substantially. Ecosocial, risk environment and dialectical theories suggest many metropolitan areas characteristics that might drive this variation. We assess metropolitan area characteristics associated with decline in mortality rates among IDUs living with AIDS (per 10,000 adult MSA residents after highly active antiretroviral therapy (HAART was developed.This is an ecological cohort study of 86 large US metropolitan areas from 1993-2006. The proportional rate of decline in mortality among IDUs diagnosed with AIDS (as a proportion of adult residents from 1993-1995 to 2004-2006 was the outcome of interest. This rate of decline was modeled as a function of MSA-level variables suggested by ecosocial, risk environment and dialectical theories. In multiple regression analyses, we used 1993-1995 mortality rates to (partially control for pre-HAART epidemic history and study how other independent variables affected the outcomes.In multivariable models, pre-HAART to HAART era increases in 'hard drug' arrest rates and higher pre-HAART income inequality were associated with lower relative declines in mortality rates. Pre-HAART per capita health expenditure and drug abuse treatment rates, and pre- to HAART-era increases in HIV counseling and testing rates, were weakly associated with greater decline in AIDS mortality.Mortality among IDUs living with AIDS might be decreased by reducing metropolitan income inequality, increasing public health expenditures, and perhaps increasing drug abuse treatment and HIV testing services. Given prior evidence that drug-related arrest rates are associated with higher HIV prevalence rates among IDUs and do not seem to decrease IDU population prevalence, changes in laws and policing practices to reduce such arrests while still protecting public order should be considered.

Cognitive and psychosocial development of HIV pediatric patients receiving highly active anti-retroviral therapy: a case-control study

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Theodoridou Maria

2010-12-01

Full Text Available Abstract Background The psychosocial development of pediatric HIV patients has not been extensively evaluated. The study objectives were to evaluate whether emotional and social functions are differentially associated with HIV-related complications. Methods A matched case-control study design was conducted. The case group (n = 20 consisted of vertically infected children with HIV (aged 3-18 years receiving HAART in Greece. Each case was matched with two randomly selected healthy controls from a school-based population. CNS imaging and clinical findings were used to identify patients with HIV-related neuroimaging abnormalities. The Wechsler Intelligence Scale III and Griffiths Mental Abilities Scales were applied to assess cognitive abilities. The age specific Strengths and Difficulties Questionnaire was used to evaluate emotional adjustment and social skills. The Fisher's exact test, student's t-test, and Wilcoxon rank sum test were used to compare categorical, continuous, and ordinal scores, respectively, of the above scales between groups. Results HIV patients without neuroimaging abnormalities did not differ from patients with neuroimaging abnormalities with respect to either age at HAART initiation (p = 0.306 or months of HAART treatment (p = 0.964. While HIV patients without neuroimaging abnormalities had similar cognitive development with their healthy peers, patients with neuroimaging abnormalities had lower mean General (p = 0.027 and Practical (p = 0.042 Intelligence Quotient scores. HIV patients without neuroimaging abnormalities had an increased likelihood of both Abnormal Emotional Symptoms (p = 0.047 and Hyperactivity scores (p = 0.0009. In contrast, HIV patients with neuroimaging abnormalities had an increased likelihood of presenting with Abnormal Peer Problems (p = 0.033. Conclusions HIV patients without neuroimaging abnormalities are more likely to experience maladjustment with respect to their emotional and activity spheres

Mesenchymal stromal cells retrovirally transduced with prodrug-converting genes are suitable vehicles for cancer gene therapy.

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Ďuriniková, E; Kučerová, L; Matúšková, M

2014-01-01

Mesenchymal stem/stromal cells (MSC) possess a set of several fairly unique properties which make them ideally suitable both for cellular therapies and regenerative medicine. These include: relative ease of isolation, the ability to differentiate along mesenchymal and non-mesenchymal lineages in vitro and the ability to be extensively expanded in culture without a loss of differentiative capacity. MSC are not only hypoimmunogenic, but they mediate immunosuppression upon transplantation, and possess pronounced anti-inflammatory properties. They are able to home to damaged tissues, tumors, and metastases following systemic administration. The ability of homing holds big promise for tumor-targeted delivery of therapeutic agents. Viruses are naturally evolved vehicles efficiently transferring their genes into host cells. This ability made them suitable for engineering vector systems for the delivery of genes of interest. MSC can be retrovirally transduced with genes encoding prodrug-converting genes (suicide genes), which are not toxic per se, but catalyze the formation of highly toxic metabolites following the application of a nontoxic prodrug. The homing ability of MSC holds advantages compared to virus vehicles which display many shortcomings in effective delivery of the therapeutic agents. Gene therapies mediated by viruses are limited by their restricted ability to track cancer cells infiltrating into the surrounding tissue, and by their low migratory capacity towards tumor. Thus combination of cellular therapy and gene delivery is an attractive option - it protects the vector from immune surveillance, and supports targeted delivery of a therapeutic gene/protein to the tumor site.

A predominance of R5-like HIV genotypes in vaginal secretions is associated with elevated plasma HIV-1 RNA levels and the absence of anti-retroviral therapy

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Lacour Nedra

2008-07-01

Full Text Available Abstract HIV expressed in genital secretions provides the inoculum from which transmitting variants are selected, both in sexual transmission and mother-to-infant transmission during partuition. Characterization of HIV levels and genotypes found in vaginal secretions and the impact of anti-retroviral therapy (ART on this virus can provide valuable insight for the prevention of HIV transmission. Vaginal HIV was evaluated in a cohort of 43 women attending a New Orleans HIV outpatient clinic. Predominant vaginal genotypes were characterized as R5- or X4-like by heteroduplex tracking analyses of the envelope V3 region. Most women (67.4% shed R5-like genotypes in vaginal secretions which was associated with elevated plasma HIV levels (≥ 10,000 copies HIV-RNA/mL and absence of ART. Because R5-like genotypes are more frequently associated with transmission, these observations suggest that the majority of women shedding HIV in genital secretions present a transmission risk. The levels of vaginal virus were similar between both groups, but shedding of X4-like genotypes was associated with lower plasma viral loads and the use of ART, suggesting that ART use may impact the genotypes of virus found in the female genital compartment.

Home is where the HAART is: an examination of factors affecting neighbourhood perceptions among people with HIV/AIDS on antiretroviral therapy.

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Vasarhelyi, Krisztina; Brandson, Eirikka K; Palmer, Alexis K; Fernandes, Kimberly A; Zhang, Wendy; Moore, David M; Montaner, Julio S G; Hogg, Robert S

2011-02-01

Understanding the neighbourhood perceptions of individuals living with HIV in urban and non-urban areas may help identify potential barriers to uptake and effectiveness of therapy. We evaluate how neighbourhood perceptions are influenced by socio-economic factors, such as food security and stable housing and other explanatory variables, among individuals receiving highly active antiretroviral therapy (HAART) in British Columbia. Neighbourhood perceptions, quality of life and socio-demographic information were collected in an interviewer-administered survey with study participants. Perception of neighbourhood problems, perception of neighbourhood cohesion and perception of relative standard of living were evaluated using previously defined scales. Bivariate and multivariate analyses were carried out to determine associations with neighbourhood perceptions, food security and stable housing. Our analyses were based on 457 participants, of whom 133 (29%) were food secure and 297 (65%) had stable housing. Mean scores for perceptions of neighbourhood problems and cohesion were 35 (IQR 15-58) and 57 (IQR 46-69), respectively. Being food secure and having stable housing was associated with a 9% and 11% decrease in perception of neighbourhood problems, respectively, and a 6% increase in the perception of neighbourhood cohesion in both cases. Food security and stable housing are related to neighbourhood perceptions among individuals on HAART. The results point to potential targets for intervention, involving improvements to living conditions such as housing and food security, which may promote treatment success for HAART, especially in marginalized communities.

HAART slows progression to anal cancer in HIV-infected MSM.

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Duncan, Katrina C; Chan, Keith J; Chiu, Connie G; Montaner, Julio S G; Coldman, Andy J; Cescon, Angela; Au-Yeung, Christopher G; Wiseman, Sam M; Hogg, Robert S; Press, Natasha M

2015-01-28

Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM. A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008. Time from first CD4 cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (cancer cases (n = 37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4 cell count nadir was 70 cells/μl (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [adjusted hazard ratio (AHR) 3.04, 95% confidence interval (95% CI) 1.48-6.24, P = 0.002], with a CD4 cell count nadir less than 100 cells/μl (AHR 2.21, 95% CI 1.06-4.62, P = 0.035) and longer duration of CD4 cell count less than 100 cells/μl (AHR 1.33, 95% CI 1.11-1.58, P = 0.002). Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART. Our results suggest that early use of HAART may delay progression to anal cancer.

The first ten years: achievements and challenges of the Brazilian program of universal access to HIV/AIDS comprehensive management and care, 1996-2006 Os primeiros dez anos: conquistas e desafios do programa brasileiro de acesso ao manejo e cuidado integral do HIV/AIDS no Brasil, 1996-2006

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Mariana A. Hacker

2007-01-01

Full Text Available A review was carried out of papers published between 1996 and 2006, documenting the introduction of highly active anti-retroviral therapy (HAART in Brazil. Papers indexed in the MEDLINE and SciELO databases were retrieved using different combinations of keywords related to the management and care of AIDS in the post-HAART era: opportunistic diseases and co-infections, adherence to therapy, survival in the pre- and post-HAART eras, adverse events and side-effects, emergence and possible transmission of resistant viral strains, metabolic and cardiovascular disorders, and issues related to access to care and equity. The review documents the dramatic changes in HIV/AIDS disease progression in the post-HAART era, including an increase in survival and quality of life and a pronounced decrease in the episodes of opportunistic diseases. Notwithstanding such major achievements, new challenges have emerged, including slow evolving co-infections (such as hepatitis C, metabolic and cardiovascular disorders, the emergence of viral resistance, with consequences at the individual level (virological failure and the community level (primary/secondary resistance at the population level, and impacts on the cost of new therapeutic regimens.Procedeu-se a uma revisão abrangente de artigos publicados entre 1996-2006, período posterior à introdução da terapia anti-retroviral de alta potência (HAART no Brasil. Foram revisados artigos disponíveis nas bases de dados MEDLINE e SciELO, a partir de combinações de palavras-chave que contemplam os principais temas na área do tratamento e manejo da AIDS na era pós-HAART: doenças oportunistas e co-infecções, aderência à terapia, sobrevida pré e pós-HAART, eventos adversos e efeitos colaterais, emergência e eventual transmissão de cepas virais resistentes e complicações cardiovasculares e metabólicas, além de questões relativas ao acesso e à eqüidade. Em suma, observa-se uma transformação profunda no

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.

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Mengist, Hylemariam Mihiretie; Taye, Bineyam; Tsegaye, Aster

2015-01-01

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 intestinal parasites significantly differed by HAART status and cryptosporidium species were found only in HAART naïve patients with low CD4+ T cell counts. Anemia was also more prevalent and significantly associated with IPs in non-HAART patients. This study identified some environmental and associated risk factors for intestinal parasitic infections. Therefore, Public health measures should continue to emphasize the importance of environmental and personal hygiene to protect HIV/AIDS patients from

Incidence of WHO stage 3 and 4 conditions following initiation of anti-retroviral therapy in resource limited settings.

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Andrea J Curtis

Full Text Available OBJECTIVES: To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART in resource limited settings (RLS. DESIGN/SETTING: A descriptive analysis of routine program data collected prospectively from 25 Médecins Sans Frontières supported HIV treatment programs in eight countries between 2002 and 2010. SUBJECTS/PARTICIPANTS: 35,349 study participants with median follow-up on ART of 1.33 years (IQR 0.51-2.41. OUTCOME MEASURES: Incidence in 100 person-years of WHO stage 3 or 4 conditions during 5 periods after ART initiation. Diagnoses of conditions were made according to WHO criteria and relied upon clinical assessments supported by basic laboratory investigations. RESULTS: The incidence of any WHO clinical stage 3 or 4 condition over 3 years was 40.02 per 100 person-years (31.77 for stage 3 and 8.25 for stage 4. The incidence of stage 3 and 4 conditions fell by over 97% between months 0-3 and months 25-36 (77.81 to 2.40 for stage 3 and 28.70 to 0.64 for stage 4. During months 0-3 pulmonary tuberculosis was the most common condition diagnosed in adults (incidence 22.24 per 100 person-years and children aged 5-14 years (25.76 and oral candidiasis was the most common in children <5 years (25.79. Overall incidences were higher in Africa compared with Asia (43.98 versus 12.97 for stage 3 and 8.98 versus 7.05 for stage 4 conditions, p<0.001. Pulmonary tuberculosis, weight loss, oral and oesophageal candidiasis, chronic diarrhoea, HIV wasting syndrome and severe bacterial infections were more common in Africa. Extra-pulmonary tuberculosis, non-tuberculous mycobacterial infection, cryptococcosis, penicilliosis and toxoplasmosis were more common in Asia. CONCLUSIONS: The incidence of WHO stage 3 and 4 conditions during the early period after ART initiation in RLS is high, but greatly reduces over time. This is likely due to both the benefits of ART and deaths of the sickest patients occurring shortly

Retroviral Vectors: Post Entry Events and Genomic Alterations

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Christof von Kalle

2011-04-01

Full Text Available The curative potential of retroviral vectors for somatic gene therapy has been demonstrated impressively in several clinical trials leading to sustained long-term correction of the underlying genetic defect. Preclinical studies and clinical monitoring of gene modified hematopoietic stem and progenitor cells in patients have shown that biologically relevant vector induced side effects, ranging from in vitro immortalization to clonal dominance and oncogenesis in vivo, accompany therapeutic efficiency of integrating retroviral gene transfer systems. Most importantly, it has been demonstrated that the genotoxic potential is not identical among all retroviral vector systems designed for clinical application. Large scale viral integration site determination has uncovered significant differences in the target site selection of retrovirus subfamilies influencing the propensity for inducing genetic alterations in the host genome. In this review we will summarize recent insights gained on the mechanisms of insertional mutagenesis based on intrinsic target site selection of different retrovirus families. We will also discuss examples of side effects occurring in ongoing human gene therapy trials and future prospectives in the field.

Insights into pathogenic events of HIV-associated Kaposi sarcoma and immune reconstitution syndrome related Kaposi sarcoma

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Lemmer Johan

2008-01-01

Full Text Available Abstract A decrease in the incidence of human immune deficiency virus-associated Kaposi sarcoma (HIV-KS and regression of some established HIV-KS lesions is evident after the introduction of highly active anti-retroviral treatment (HAART, and is attributed to generalized immune restoration, to the reconstitution of human herpesvirus (HHV-8 specific cellular immune responses, and to the decrease in HIV Tat protein and HHV-8 loads following HAART. However, a small subset of HIV-seropositive subjects with a low CD4+ T cell count at the time of introduction of HAART, may develop HIV-KS as immune reconstitution inflammatory syndrome (IRIS within 8 weeks thereafter.

Adverse drug reaction in HIV-infected people treated with HAART in ...

African Journals Online (AJOL)

-infected patients on prolonged treatment with highly active antiretroviral therapy (HAART) at a public health facility in Maringá, Southern Brazil. Methods: A retrospective and prospective analysis of laboratory results and clinical ...

Access to highly active antiretroviral therapy (HAART) for injecting drug users in the WHO European Region 2002-2004

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Donoghoe, Martin C; Bollerup, Annemarie R; Lazarus, Jeff

2007-01-01

Providing equitable access to highly active antiretroviral treatment (HAART) to injecting drug users (IDUs) is both feasible and desirable. Given the evidence that IDUs can adhere to HAART as well as non-IDUs and the imperative to provide universal and equitable access to HIV/AIDS treatment for all...... who need it, here we examine whether IDUs in the 52 countries in the WHO European Region have equitable access to HAART and whether that access has changed over time between 2002 and 2004. We consider regional and country differences in IDU HAART access; examine preliminary data regarding...

Causes of death in HIV infection: the key determinant to define the clinical response to anti-HIV therapy

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Mocroft, Amanda; Gatell, Jose; Reiss, Peter; Ledergerber, Bruno; Kirk, Ole; Vella, Stefano; Blaxhult, Anders; Phillips, Andrew N.; Lundgren, Jens

2004-01-01

Studies have shown an increased risk of new AIDS/death among injecting drug users (IDU) starting highly active antiretroviral therapy (HAART). Of 3872 patients starting HAART in the EuroSIDA study, 819 were IDU (21.2%). During 14 769 person-years of follow-up, 499 patients progressed to new

Long-Term Effect of HAART on Biochemical Profiles of HIV/AIDS ...

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Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. ... Purpose: To assess the long-term effect of highly active antiretroviral therapy (HAART) on .... allowed to clot at room temperature for 45 min.

Effect of anemia on hepatotoxicity of HAART in HIV patients in Benin ...

African Journals Online (AJOL)

Background: Hepatotoxicity is a relevant adverse effect of highly active antiretroviral Treatment owing to its frequency, and it can cause interruption of therapy, hepatitis, and death. There is dearth of information on hepatotoxicity arising from highly active antiretroviral therapy (HAART) in anemic patients. Anemia is the most ...

Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART

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O'Sullivan, Cathal E.; Peng, RongSheng; Cole, Kelly Stefano; Montelaro, Ronald C.; Sturgeon, Timothy; Jenson, Hal B.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

2002-01-01

Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months. Copyright 2002 Wiley-Liss, Inc.

Assessing the effect of HAART on change in quality of life among HIV-infected women

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Hu Zheng

2006-03-01

Full Text Available Abstract Background The impact of highly active antiretroviral therapy (HAART on health-related quality of life (QOL of HIV-1 infected individuals in large prospective cohorts has not been well studied. Objective To assess the effect of HAART on QOL by comparing HIV-infected women using HAART with HIV-infected women remaining HAART naïve in the Women's Interagency HIV Study (WIHS, a multicenter prospective cohort study begun in 1994 in the US. Methods A 1:1 matching with equivalent (≤ 0.1% propensity scores for predicting HAART initiation was implemented and 458 pairs were obtained. HAART effects were assessed using pattern mixture models. The changes of nine QOL domain scores and one summary score derived from a shortened version of the MOS-HIV from initial values were used as study outcomes. Results The background covariates of the treatment groups were well-balanced after propensity score matching. The 916 matched subjects had a mean age of 38.5 years and 42% had a history of AIDS diagnosis. The participants contributed a total of 4,292 person visits with a median follow-up time of 4 years. In the bivariate analyses with only HAART use and time as covariates, HAART was associated with short-term improvements of 4 QOL domains: role functioning, social functioning, pain and perceived health index. After adjusting for demographic, socioeconomic, biological and clinical variables, HAART had small but significant short-term improvements on changes in summary QOL (mean change: 3.25; P = 0.02, role functioning (6.99; P P P = 0.03, pain (6.73; P P = 0.03 and perceived health index (4.87; P Conclusion Our study demonstrated significant short-term HAART effects on most QOL domains, but additional use of HAART did not modify long-term trends. These changes could be attributed to the direct effect of HAART and indirect HAART effect mediated through clinical changes.

Audiological and electrophysiological alterations in HIV-infected individuals subjected or not to antiretroviral therapy.

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Matas, Carla Gentile; Samelli, Alessandra Giannella; Magliaro, Fernanda Cristina Leite; Segurado, Aluisio

2017-08-02

The Human Immunodeficiency Virus (HIV) and infections related to it can affect multiple sites in the hearing system. The use of High-Activity Anti-Retroviral Therapy (HAART) can cause side effects such as ototoxicity. Thus, no consistent patterns of hearing impairment in adults with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome have been established, and the problems that affect the hearing system of this population warrant further research. This study aimed to compare the audiological and electrophysiological data of Human Immunodeficiency Virus-positive patients with and without Acquired Immune Deficiency Syndrome, who were receiving High-Activity Anti-Retroviral Therapy, to healthy individuals. It was a cross-sectional study conducted with 71 subjects (30-48 years old), divided into groups: Research Group I: 16 Human Immunodeficiency Virus-positive individuals without Acquired Immunodeficiency Syndrome (not receiving antiretroviral treatment); Research Group II: 25 Human Immunodeficiency Virus-positive individuals with Acquired Immunodeficiency Syndrome (receiving antiretroviral treatment); Control Group: 30 healthy subjects. All individuals were tested by pure-tone air conduction thresholds at 0.25-8kHz, extended high frequencies at 9-20kHz, electrophysiological tests (Auditory Brainstem Response - ABR, Middle Latency Responses - MLR, Cognitive Potential - P300). Research Group I and Research Group II had higher hearing thresholds in both conventional and high frequency audiometry when compared to the control group, prolonged latency of waves I, III, V and interpeak I-V in Auditory Brainstem Response and prolonged latency of P300 Cognitive Potential. Regarding Middle Latency Responses, there was a decrease in the amplitude of the Pa wave of Research Group II compared to the Research Group I. Both groups with Human Immunodeficiency Virus had higher hearing thresholds when compared to healthy individuals (group exposed to antiretroviral

Evaluation of oral manifestations and oral health status among pediatric human immunodeficiency virus patients-under anti-retroviral therapy: A cross-sectional study

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Monika Aroquiadasse

2016-01-01

Full Text Available Introduction: The human immunodeficiency virus (HIV acquired immunodeficiency syndrome disease has evolved to become a social and economic catastrophe, with far-reaching implications affecting every phase of life of the diseased individual. Data on adults and children diagnosed with HIV infection are useful for determining populations needing prevention and treatment services. Oral lesions may be the presenting symptoms of HIV infection and may differ entirely from those manifested in the adult population. Aim and Objective: We aimed to evaluate the prevalence of HIV related oral lesions among pediatric HIV patients and to assess the oral health status of HIV infected children residing in a selected childcare facility in Puducherry. Materials and Methods: A cross-sectional study was conducted during September 2015 in child care facility for HIV infected children located in Puducherry U.T, India. All children <18 years, who are diagnosed with HIV infection and are put on anti-retroviral therapy (ART or pre-ART care, were included in the study. After obtaining informed consent from the care-givers and assent of the children, they were interviewed and examined by a team comprising a qualified dental surgeon and a trained physician. Results: Majority of the children were under first-line ART (73% and were on ART for more than 4 years. The CD4 count of 23 (52.3 was between 500–1000 cells/μL. The recent viral load assay in 32 (72.7 patients was <150/not detected. Tooth decay was the most common oral manifestation with 28 (63.6 being affected. Nonspecific lymphadenopathy 26 (59.1 was the most common coexisting systemic illness. Conclusion: This study proves that constant surveillance by monitoring the general health status, CD4 counts, viral load coupled with stringent ART care has improved the overall quality of life of these children and consequently resulted in lesser oral manifestations.

Impact of maternal anti retroviral drugs during pregnancy on risk of ...

African Journals Online (AJOL)

A reason proffered for the association of pretenn births and antiretrovirals is the Th2 to Th1 eytokine shift associated with HAART administration. Successful pregnancies are characterized by a Th1 to Th2 cytokine shift. Other associated factors were immunosuppression, multiple pregnancies and other psychosocial factors ...

Vestibular function in a group of adults with HIV/AIDS on HAART ...

African Journals Online (AJOL)

Materials and Methods: The main aim of the current study was to investigate and monitor the vestibular status in a group of adult patients with AIDS receiving Highly Active Antiretroviral Therapy (HAART) and other therapies in a hospital outpatient clinic in Gauteng, South Africa. The study was exploratory and observational ...

Supporting children to adhere to anti-retroviral therapy in urban Malawi: multi method insights

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Phiri Sam

2009-07-01

Full Text Available Abstract Background Ensuring good adherence is critical to the success of anti-retroviral treatment (ART. However, in resource-poor contexts, where paediatric HIV burden is high there has been limited progress in developing or adapting tools to support adherence for HIV-infected children on ART and their caregivers. We conducted formative research to assess children's adherence and to explore the knowledge, perceptions and attitudes of caregivers towards children's treatment. Methods All children starting ART between September 2002 and January 2004 (when ART was at cost in Malawi were observed for at least 6 months on ART. Their adherence was assessed quantitatively by asking caregivers of children about missed ART doses during the previous 3 days at monthly visits. Attendance to clinic appointments was also monitored. In June and July 2004, four focus group discussions, each with 6 to 8 caregivers, and 5 critical incident narratives were conducted to provide complementary contextual data on caregivers' experiences on the challenges to and opportunities of paediatric ART adherence. Results We followed prospectively 47 children who started ART between 8 months and 12 years of age over a median time on ART of 33 weeks (2–91 weeks. 72% (34/47 never missed a single dose according to caregivers' report and 82% (327/401 of clinic visits were either as scheduled, or before or within 1 week after the scheduled appointment. Caregivers were generally knowledgeable about ART and motivated to support children to adhere to treatment despite facing multiple challenges. Caregivers were particularly motivated by seeing children begin to get better; but faced challenges in meeting the costs of medicine and transport, waiting times in clinic, stock outs and remembering to support children to adhere in the face of multiple responsibilities. Conclusion In the era of rapid scale-up of treatment for children there is need for holistic support strategies that focus

Challenges, coping strategies, and recommendations related to the HIV services field in the HAART era: a systematic literature review of qualitative studies from the United States and Canada.

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Kerr, Zachary Y; Miller, Katye R; Galos, Dylan; Love, Randi; Poole, Charles

2013-02-01

Qualitative research methods have been utilized to study the nature of work in the HIV services field. Yet current literature lacks a Highly Active Anti-Retroviral Treatment (HAART) era compendium of qualitative research studying challenges and coping strategies in the field. This study systematically reviewed challenges and coping strategies that qualitative researchers observed in the HIV services field during the HAART era, and their recommendations to organizations. Four online databases were searched for peer-reviewed research that utilized qualitative methods, were published from January 1998 to February 2012, utilized samples of individuals in the HIV services field; occurred in the U.S. or Canada, and contained information related to challenges and/or coping strategies. Abstracts were identified (n=846) and independently read and coded for inclusion by at least two of the four first authors. Identified articles (n=26) were independently read by at least two of the four first authors who recorded the study methodology, participant demographics, challenges and coping strategies, and recommendations. A number of challenges affecting those in the HIV services field were noted, particularly interpersonal and organizational issues. Coping strategies were problem- and emotion-focused. Summarized research recommendations called for increased support, capacity-building, and structural changes. Future research on challenges and coping strategies must provide up-to-date information to the HIV services field while creating, implementing, and evaluating interventions to manage current challenges and reduce the risk of burnout.

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.

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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

A Comparative Study of Salivary Composition of HIV Seropositive Patients on HAART and Not on HAART

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Navdeep Johar

2011-01-01

Conclusions: This preliminary study suggests that HAART does not significantly after the composition of saliva. Further, larger studies are required to study the effect of HAART on salivary gland function.

"Every drug goes to treat its own disease…" - a qualitative study of perceptions and experiences of taking anti-retrovirals concomitantly with anti-malarials among those affected by HIV and malaria in Tanzania

DEFF Research Database (Denmark)

Mangesho, Peter E; Reynolds, Joanna; Lemnge, Martha

2014-01-01

BACKGROUND: Little is known about how people living with human immunodeficiency virus (HIV) experience malaria and the concomitant use of anti-malarial treatments with anti-retrovirals (ARVs). An understanding of how patients make sense of these experiences is important to consider in planning......, perceptions of drug strength appeared to compel some people not enrolled in the clinical study to take the drugs at separate times to avoid anticipated harm to the body. CONCLUSIONS: Management of HIV and malaria concurrently often requires individuals to cross the domains of different disease programmes...

HAART impact on prevalence of chronic otitis media in Brazilian HIV-infected children.

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Weber, Raimar; Pinheiro Neto, Carlos Diógenes; Miziara, Ivan Dieb; Araújo Filho, Bernardo Cunha

2006-01-01

The advent of new antiretroviral drugs such as protease inhibitors has generated sensible changes in morbity and mortality in HIV-infected patients. To evaluate the impact of Highly Active Antiretroviral Therapy (HAART) on the prevalence of chronic otitis media in HIV-infected pediatric population. We analyzed medical charts of 471 children aged zero to 12 years and 11 months with HIV infection from an Ambulatory of ENT and AIDS. Children were divided according to the age: 0 to 5 years and 11 months and 6 to 12 years and 11 months and classified as having chronic otitis media based on history, physical examination, audiologic and tympanometric data. Prevalence of chronic otitis media, as well as CD4+ lymphocyte count were compared between groups in use of HAART and the group without HAART. Out of 459 children, 65 (14.2%) had chronic otitis media. We observed that in children aged 0 to 5 years and 11 months who were taking HAART there was significant lower prevalence of chronic otitis media (p=0.02). The use of HAART was associated to higher mean CD4+ lymphocyte count (pmedia in HIV infected children, probably due to increase in mean CD4+ lymphocyte count.

Morphological changes in the digestive system of 322 necropsies of patients with acquired immune deficiency syndrome: comparison of findings pre- and post-HAART (Highly Active Antiretroviral Therapy).

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Guimarães, Lucinda Calheiros; Silva, Ana Cristina Araújo Lemos da; Micheletti, Adilha Misson Rua; Moura, Everton Nunes Melo; Silva-Vergara, Mario Léon; Tostes, Sebastião; Adad, Sheila Jorge

2017-04-03

Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases); B - one or two antiretroviral drugs or HAART for less than six months (83 cases); C - HAART for six months or longer (54 cases). In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%), followed by cytomegalovirus (19.2%), Histoplasma capsulatum (6.5%), mycobacteria (5.6%), and Toxoplasma gondii (4.3%). T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV) was more frequent in group A compared with groups B and C (p digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy.

Prevalence of lipodystrophy and metabolic syndrome among HIV positive individuals on Highly Active Anti-Retroviral treatment in Jimma, South West Ethiopia.

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Berhane, Tsegay; Yami, Alemishet; Alemseged, Fessahaye; Yemane, Tilahun; Hamza, Leja; Kassim, Mehedi; Deribe, Kebede

2012-01-01

Use of highly active antiretroviral therapy has led to significant reductions in morbidity and mortality rates. However, these agents had also given rise to the metabolic and morphologic abnormalities which are modifiable risk factors for cardiovascular diseases. Evidences elsewhere indicate growing in prevalence of these problems but studies are lacking in Ethiopia. This study was conducted to determine the prevalence of HIV-associated lipodystrophy and metabolic syndrome in patients taking highly active antiretroviral therapy. A cross-sectional study was conducted in 2010 on a sample of 313 patients taking highly active antiretroviral therapy in Jimma University specialized hospital. Structured questionnaire was used to assess patients' sociodemographic characteristics and clinical manifestations of metabolic abnormalities. Checklists were used for reviewing charts about clinical manifestations of metabolic abnormalities and immunologic profile of patients. Data was cleaned, entered in and analyzed using SPSS for windows version 16.0. Metabolic syndrome was detected in 21.1% and HIV-lipodystrophy was detected 12.1% of patients. The factors found to be independently associated with metabolic syndrome were taking the antiretroviral therapy for more than 12 months (AOR=4.2; 95% CI=1.24-14.23) and female sex (AOR=2.30; 95% CI=1.0-5.27) and the factor found to be independently associated with HIV-lipodystrophy was taking the antiretroviral therapy (AOR=3.59; 95% CI=1.03-12.54) for more than 12 months. Metabolic abnormalities were relatively common in the study population. The problems were higher among those who took anti-retroviral treatment for longer duration. Therefore, regular screening for and taking action against the metabolic abnormalities is mandatory.

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

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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.

Analyzing the Genotoxicity of Retroviral Vectors in Hematopoietic Cell Gene Therapy

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Luca Biasco

2018-03-01

Full Text Available Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face severe adverse events in the form of leukemias and myelodysplastic syndromes, related to the semi-random vector integration into the host cell genome that caused deregulation of neighboring proto-oncogenes. Although improvements in vector design clearly lowered the risk of this insertional mutagenesis, analysis of potential genotoxicity and the consequences of vector integration remain important parameters for basic and translational research and most importantly for the clinic. Here, we review current assays to analyze biodistribution and genotoxicity in the pre-clinical setting and describe tools to monitor vector integration sites in vector-treated patients as a biosafety readout.

Anti-inflammatory and vasoprotective activity of a retroviral-derived peptide, homologous to human endogenous retroviruses: endothelial cell effects.

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George J Cianciolo

Full Text Available Malignant and inflammatory tissues sometimes express endogenous retroviruses or their proteins. A highly-conserved sequence from retroviral transmembrane (TM proteins, termed the "immunosuppressive domain (ID", is associated with inhibition of immune and inflammatory functions. An octadecapeptide (MN10021 from the ID of retroviral TM protein p15E inhibits in vitro release of pro-inflammatory cytokines and increases synthesis of anti-inflammatory IL-10. We sought to determine if MN10021 has significant in vivo effects. MN10021, prepared by solid-phase synthesis, was dimerized through a naturally-occurring, carboxy-terminal cysteine. In vivo anti-inflammatory activity was determined using a murine model of sodium periodate (NaIO(4-induced peritonitis. In vivo vasoprotective effects were determined using: (1 a carrageenan-induced model of disseminated intravascular coagulation (DIC in mice; (2 a reverse passive Arthus model in guinea pigs; and (3 vasoregulatory effects in spontaneously hypertensive rats (SHR. In vitro studies included: (1 binding/uptake of MN10021 using human monocytes, cultured fibroblasts, and vascular endothelial cells (VEC; (2 gene expression by RT-PCR of MN10021-treated VEC; and (3 apoptosis of MN10021-treated VEC exposed to staurosporine or TNF-α. One-tenth nmol MN10021 inhibits 50 percent of the inflammatory response in the mouse peritonitis model. Furthermore, 73 nmol MN10021 completely protects mice in a lethal model of carrageenan-induced DIC and inhibits vascular leak in both the mouse DIC model and a guinea pig reverse passive Arthus reaction. MN10021 binds to and is taken up in a specific manner by both human monocytes and VEC but not by cultured human fibroblasts. Surprisingly, orally-administered MN10021 lowers blood pressure in SHR rats by 10-15% within 1 h suggesting a direct or indirect effect on the vascular endothelium. MN10021 and derived octapeptides induce iNOS (inducible nitric oxide synthase mRNA in VEC

Inhibition of HIV-1 entry by extracts derived from traditional Chinese medicinal herbal plants

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Song Xinming

2009-08-01

Full Text Available Abstract Background Highly active anti-retroviral therapy (HAART is the current HIV/AIDS treatment modality. Despite the fact that HAART is very effective in suppressing HIV-1 replication and reducing the mortality of HIV/AIDS patients, it has become increasingly clear that HAART does not offer an ultimate cure to HIV/AIDS. The high cost of the HAART regimen has impeded its delivery to over 90% of the HIV/AIDS population in the world. This reality has urgently called for the need to develop inexpensive alternative anti-HIV/AIDS therapy. This need has further manifested by recent clinical trial failures in anti-HIV-1 vaccines and microbicides. In the current study, we characterized a panel of extracts of traditional Chinese medicinal herbal plants for their activities against HIV-1 replication. Methods Crude and fractionated extracts were prepared from various parts of nine traditional Chinese medicinal herbal plants in Hainan Island, China. These extracts were first screened for their anti-HIV activity and cytotoxicity in human CD4+ Jurkat cells. Then, a single-round pseudotyped HIV-luciferase reporter virus system (HIV-Luc was used to identify potential anti-HIV mechanisms of these extracts. Results Two extracts, one from Euphorbiaceae, Trigonostema xyphophylloides (TXE and one from Dipterocarpaceae, Vatica astrotricha (VAD inhibited HIV-1 replication and syncytia formation in CD4+ Jurkat cells, and had little adverse effects on host cell proliferation and survival. TXE and VAD did not show any direct inhibitory effects on the HIV-1 RT enzymatic activity. Treatment of these two extracts during the infection significantly blocked infection of the reporter virus. However, pre-treatment of the reporter virus with the extracts and treatment of the extracts post-infection had little effects on the infectivity or gene expression of the reporter virus. Conclusion These results demonstrate that TXE and VAD inhibit HIV-1 replication likely by blocking

The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters

NARCIS (Netherlands)

Martinez, Esteban; Visnegarwala, Fehmida; Grund, Birgit; Thomas, Avis; Gibert, Cynthia; Shlay, Judith; Drummond, Fraser; Pearce, Daniel; Edwards, Simon; Reiss, Peter; El-Sadr, Wafaa; Carr, Andrew

2010-01-01

Objective: To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters. Design: Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or

Metabolic Disturbances in Liver {sup 1}H MR Spectroscopy in HIV and HCV Co-infected Patients as a Potential Marker of Hepatocyte Activation

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Tarasow, E.; Wierciska-Drapao, A.; Jaroszewicz, J.; Siergiejczyk, L.; Orzechowska-Bobkiewicz, A.; Prokopowicz, D.; Walecki, J. [Medical Academy Hospital, Bialystok (Poland). Dept. of Radiology

2004-12-01

Purpose : To evaluate proton magnetic resonance spectroscopy ({sup 1}H MRS) features in order to assess hepatocellular activation in chronic hepatitis C and human immunodeficiency virus/hepatitis C (HIV/HCV) co-infected patients. Material and Methods : Liver in vivo {sup 1}H MR spectra were obtained in 14 patients with hepatitis C virus infection (HCV), 20 HIV/HCV co-infected individuals, and 24 healthy volunteers. Resonances of lipids, glutamine/glutamate (Glx), phosphomonoesters (PME), glycogen/glucose (Glc) were assessed and metabolite ratios to total lipids (TL) were calculated. Results : A significant increase in Glx/TL and PME/TL was observed in the HCV group as compared to healthy individuals. Patients with HIV and HCV co-infection had a further increase of all metabolite ratios. Changes in metabolite ratios were due to both the increase in particular metabolite contents and to the decrease in lipid levels. HIV/HCV-infected patients treated with highly active anti-retroviral therapy (HAART) showed elevated PME and Glx levels and significantly decreased TL compared to patients not undergoing anti-retroviral treatment. Conclusions : Our findings suggest clinical usefulness of liver {sup 1}H MR spectroscopy in detecting even slight disturbances in liver metabolism.

Metabolic Disturbances in Liver 1H MR Spectroscopy in HIV and HCV Co-infected Patients as a Potential Marker of Hepatocyte Activation

International Nuclear Information System (INIS)

Tarasow, E.; Wierciska-Drapao, A.; Jaroszewicz, J.; Siergiejczyk, L.; Orzechowska-Bobkiewicz, A.; Prokopowicz, D.; Walecki, J.

2004-01-01

Purpose : To evaluate proton magnetic resonance spectroscopy ( 1 H MRS) features in order to assess hepatocellular activation in chronic hepatitis C and human immunodeficiency virus/hepatitis C (HIV/HCV) co-infected patients. Material and Methods : Liver in vivo 1 H MR spectra were obtained in 14 patients with hepatitis C virus infection (HCV), 20 HIV/HCV co-infected individuals, and 24 healthy volunteers. Resonances of lipids, glutamine/glutamate (Glx), phosphomonoesters (PME), glycogen/glucose (Glc) were assessed and metabolite ratios to total lipids (TL) were calculated. Results : A significant increase in Glx/TL and PME/TL was observed in the HCV group as compared to healthy individuals. Patients with HIV and HCV co-infection had a further increase of all metabolite ratios. Changes in metabolite ratios were due to both the increase in particular metabolite contents and to the decrease in lipid levels. HIV/HCV-infected patients treated with highly active anti-retroviral therapy (HAART) showed elevated PME and Glx levels and significantly decreased TL compared to patients not undergoing anti-retroviral treatment. Conclusions : Our findings suggest clinical usefulness of liver 1 H MR spectroscopy in detecting even slight disturbances in liver metabolism

Addressing the fear and consequences of stigmatization - a necessary step towards making HAART accessible to women in Tanzania: a qualitative study

OpenAIRE

Theilgaard, Zahra P; Katzenstein, Terese L; Chiduo, Mercy G; Pahl, Christiane; Bygbjerg, Ib C; Gerstoft, Jan; Lemnge, Martha M; Tersbøl, Britt P

2011-01-01

Abstract Background Highly Active Antiretroviral Therapy (HAART) has been available free of charge in Tanga, Tanzania since 2005. However we have found that a high percentage of women referred from prevention of mother-to-child transmission services to the Care and Treatment Clinics (CTC) for HAART never registered at the CTCs. Few studies have focused on the motivating and deterring factors to presenting for HAART particularly in relation to women. This study seeks to remedy this gap in know...

Pilot, randomized study assessing safety, tolerability and efficacy of simplified LPV/r maintenance therapy in HIV patients on the 1 PI-based regimen.

Science.gov (United States)

Cahn, Pedro; Montaner, Julio; Junod, Patrice; Patterson, Patricia; Krolewiecki, Alejandro; Andrade-Villanueva, Jaime; Cassetti, Isabel; Sierra-Madero, Juan; Casiró, Arnaldo David; Bortolozzi, Raul; Lupo, Sergio Horacio; Longo, Nadia; Rampakakis, Emmanouil; Ackad, Nabil; Sampalis, John S

2011-01-01

To compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART) with a ritonavir-boosted protease inhibitor (PI/r) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs) to lopinavir/ritonavir (LPV/r) monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART. This is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL), time-to-virologic rebound, patient-reported outcomes (PROs) and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE). Forty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/r;32:HAART) patients completed treatment, while 9(2:LPV/r;7:HAART) discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98%) patients on LPV/r and 37(95%) on HAART had VL<200 copies/mL (P = 0.61). Time-to-virologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%), headache (18%) and influenza (16%). Four (10%) patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/r;3:HAART) patients. At day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re-introduction upon viral rebound, in

Pilot, randomized study assessing safety, tolerability and efficacy of simplified LPV/r maintenance therapy in HIV patients on the 1 PI-based regimen.

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Pedro Cahn

Full Text Available To compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART with a ritonavir-boosted protease inhibitor (PI/r and 2 nucleoside reverse-transcriptase inhibitors (NRTIs to lopinavir/ritonavir (LPV/r monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART.This is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL, time-to-virologic rebound, patient-reported outcomes (PROs and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE.Forty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/r;32:HAART patients completed treatment, while 9(2:LPV/r;7:HAART discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98% patients on LPV/r and 37(95% on HAART had VL<200 copies/mL (P = 0.61. Time-to-virologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%, headache (18% and influenza (16%. Four (10% patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/r;3:HAART patients.At day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re-introduction upon viral rebound, in

The immunological response of HIV-positive patients initiating HAART at the Komfo Anokye Teaching Hospital, Kumasi, Ghana.

Science.gov (United States)

Annison, L; Dompreh, A; Adu-Sarkodie, Y

2013-12-01

The study sought to document the experience of immunological improvement among Ghanaian PLHIV on HAART comparing different categories of patients. Serology Unit, Komfo Anokye Teaching Hospital, Kumasi, Ghana. The study comprised a convenient sample of 303 treatment naïve HIV patients due to start HAART. Questionnaires were used to collect patient demographic and clinical data. Four CD4 counts were measured at six-monthly intervals to determine rates of CD4 change. These were pre-therapy, 1(st) post-therapy, 2(nd) post-therapy, and 3(rd) post-therapy counts. The rates of CD4 change among the different categories of patients were also compared. At baseline, women had higher CD4 count (mean of 77.4 cells/μl), and mean age of participants was 40 years. The CD4 count increased from a mean baseline of 70.2 cells/μl to 229.2, 270.0, and 297.6 cells/μl at 6, 12, and 18 months of treatment respectively (P response. There was no difference (P=0.18) in treatment response comparing those with CD4 immunological recovery during 12 months of treatment The study, therefore, concludes that significant immunological improvement is possible among Ghanaian PLHIV on HAART as long as a high level of treatment adherence is observed.

Nurses' perceptions about Botswana patients' anti-retroviral therapy adherence

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Esther Kip

2009-09-01

Opsomming Anti-retrovirale middels (ARMs word gratis verskaf in Botswana. Lewenslange getroue nakoming van ARM voorskrifte is noodsaaklik om die pasiënt se algehele staat van welsyn te verbeter en om die ontwikkeling te voorkom van stamme van die menslike immuun-gebrek virus (MIV wat weerstand bied teen anti-retrovirale behandeling (ARB. Persone met ARB-weerstandbiedende MIV stamme kan dit versprei na ander mense toe, wat duurder ARB vereis met swakker gesondheidsuitkomste. Die doel van hierdie verkennende, beskrywende, kwalitatiewe studie was om te bepaal wat verpleegkundiges se sienings is oor pasiënte in Botswana se nakoming van ARB, en om faktore te identifiseer wat die ARB-nakoming kan bevorder of benadeel. Vier ARB terreine was ewekansig gekies en al 16 verpleegkundiges wat ARB dienste by die terreine verskaf, het deelgeneem aan semi-gestruktureerde onderhoude. Hierdie verleegkundiges het aangedui dat pasiënte se ARB handhawing beïnvloed word deur diens-verwante en pasiënt-verwante faktore. Diens-verwante faktore behels die ontoeganklikheid van ARB klinieke, beperkte kliniekure, gesondheidswerkers se onvermoë om in pasiënte se plaaslike tale te kommunikeer, lang wagtye by klinieke en vertragings om ingelig te word oor uitslae van CD4 en virale tellings. Verpleegkundiges kan nie pasiënte opvolg of telefonies kontak wat versuim om op te daag vir behandeling nie. Verpleegkundiges moet nagskofte werk wat pasiënt-verpleegkundige verhoudings onderbreek. Pasiënt-verwante faktore behels pasiënte se gebrekkige opvoeding, hulle onvermoë om die belangrikheid van uitslae van CD4 en virale tellings te verstaan, finansiële ontberinge, nie-openbaarmaking en nie-aanvaarding van hulle MIV positiewe status, alkohol misbruik, die gebruik van tradisionele medisynes en die newe-effekte van ARB. Die uitdagings van lewenslange ARB handhawing is veelsydig en behels beide pasiënt-verwante en diens-verwante faktore. Die verskaffing van gratis ARMs verseker nie ARB

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.

Pilot, Randomized Study Assessing Safety, Tolerability and Efficacy of Simplified LPV/r Maintenance Therapy in HIV Patients on the 1st PI-Based Regimen

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Cahn, Pedro; Montaner, Julio; Junod, Patrice; Patterson, Patricia; Krolewiecki, Alejandro; Andrade-Villanueva, Jaime; Cassetti, Isabel; Sierra-Madero, Juan; Casiró, Arnaldo David; Bortolozzi, Raul; Lupo, Sergio Horacio; Longo, Nadia; Rampakakis, Emmanouil; Ackad, Nabil; Sampalis, John S.

2011-01-01

Objectives To compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART) with a ritonavir-boosted protease inhibitor (PI/r) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs) to lopinavir/ritonavir (LPV/r) monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART. Methods This is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL), time-to-virologic rebound, patient-reported outcomes (PROs) and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE). Results Forty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/r;32:HAART) patients completed treatment, while 9(2:LPV/r;7:HAART) discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98%) patients on LPV/r and 37(95%) on HAART had VL<200copies/mL (P = 0.61). Time-to-virologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%), headache (18%) and influenza (16%). Four (10%) patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/r;3:HAART) patients. Conclusion At day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re

Impact of Non-HIV and HIV Risk Factors on Survival in HIV-Infected Patients on HAART: A Population-Based Nationwide Cohort Study

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Obel, Niels; Omland, Lars Haukali; Kronborg, Gitte

2011-01-01

We determined the impact of three factors on mortality in HIV-infected patients who had been on highly active antiretroviral therapy (HAART) for at least one year: (1) insufficient response to (HAART) and presence of AIDS-defining diseases, (2) comorbidity, and (3) drug and alcohol abuse...

Follistatin allows efficient retroviral-mediated gene transfer into rat liver

International Nuclear Information System (INIS)

Borgnon, Josephine; Djamouri, Fatima; Lorand, Isabelle; Rico, Virginie Di; Loux, Nathalie; Pages, Jean-Christophe; Franco, Dominique; Capron, Frederique; Weber, Anne

2005-01-01

Retroviral vectors are widely used tools for gene therapy. However, in vivo gene transfer is only effective in dividing cells, which, in liver, requires a regenerative stimulus. Follistatin is effective in promoting liver regeneration after 90% and 70% hepatectomy in rats. We studied its efficacy on liver regeneration and retroviral-mediated gene delivery in 50% hepatectomized rats. When human recombinant follistatin was infused into the portal vein immediately after 50% hepatectomy, hepatocyte proliferation was significantly higher than in control 50% hepatectomized rats. A single injection of virus particles administered 23 h after follistatin infusion resulted in more than 20% gene transduction efficiency in hepatocytes compared to 3% in control rats. It is concluded that a single injection of follistatin induces onset of proliferation in 50% hepatectomized rats and allows efficient retroviral-mediated gene transfer to the liver

Morphological changes in the digestive system of 322 necropsies of patients with acquired immune deficiency syndrome: comparison of findings pre- and post-HAART (Highly Active Antiretroviral Therapy

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Lucinda Calheiros Guimarães

Full Text Available ABSTRACT Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases; B - one or two antiretroviral drugs or HAART for less than six months (83 cases; C - HAART for six months or longer (54 cases. In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%, followed by cytomegalovirus (19.2%, Histoplasma capsulatum (6.5%, mycobacteria (5.6%, and Toxoplasma gondii (4.3%. T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV was more frequent in group A compared with groups B and C (p < 0.05; 2.2% of the deaths were due to gastrointestinal bleeding. Regarding the segments, only in the large intestine, and only cytomegalovirus, were more frequent in group A compared with group C. We conclude that digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy.

Construction and characterization in vitro of a bicistronic retroviral vector coding endostatin and interleukin-2 for use in gene therapy

International Nuclear Information System (INIS)

Calvo, Fernanda Bernardes

2009-01-01

Gene therapy has been used in preclinical studies and clinical trials in order to alleviate or cure a disease. Retroviral vectors are a tool for gene transfer is widely used. Bicistronic vectors are an attractive alternative for treatment of complex diseases. A variety of options exists to simultaneously express two genes in genetically modified cells. The most common approach relies on bicistronic vectors in which the genes are linked to each other by an internal ribosome entry site allowing co-translational expression of both cistrons. Endostatin, the C-terminal fragment of collagen XVIII, is a potent angiogenesis inhibitor. At present, ES has been widely used in anti-angiogenic in a variety of experimental tumor models, and clinical trials to test it as an anti-tumor agent are already under way. Immunotherapy has been used as adjuvant treatment for tumors and has been used in several preclinical studies and clinical trials. The objective of this project was to construct and characterize 'in vitro' an IRES-based bicistronic retroviral vector encoding endostatin and interleukin-2. The construction of the vector was performed in three stages, the final construction was analyzed by restriction analysis and sequencing. Packaging cells were prepared. The endostatin and interleukin-2 levels were determined by Dot blot. Monocistronic and bicistronic mRNA expression were analyzed by real time RT-PCR. Bicistronic vector showed high levels of virus trites, ranging from 4.20x10 5 to 1.53x10 6 UFC/ml. Secreted levels of endostatin and interleukin-2 ranged from 1.08 to 2.08μg/10 6 cells.24h and 0.66 - 0.89μg/10 6 cells.24h, respectively. The mRNA expression of ES in the NIH3T3 clone pLend-IRES-IL2SN was 2 times higher than the level presented by the NIH3T3 clone pLendSN. The endostatin promoted inhibition (40%) of endothelial cell proliferation. Interleukin-2 promoted a proliferation of 10.6% lymphocytes CD4 and 8.9% of CD8. We conclude that the IRES bicistronic vector

Integration Site and Clonal Expansion in Human Chronic Retroviral Infection and Gene Therapy

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Niederer, Heather A.; Bangham, Charles R. M.

2014-01-01

Retroviral vectors have been successfully used therapeutically to restore expression of genes in a range of single-gene diseases, including several primary immunodeficiency disorders. Although clinical trials have shown remarkable results, there have also been a number of severe adverse events involving malignant outgrowth of a transformed clonal population. This clonal expansion is influenced by the integration site profile of the viral integrase, the transgene expressed, and the effect of the viral promoters on the neighbouring host genome. Infection with the pathogenic human retrovirus HTLV-1 also causes clonal expansion of cells containing an integrated HTLV-1 provirus. Although the majority of HTLV-1-infected people remain asymptomatic, up to 5% develop an aggressive T cell malignancy. In this review we discuss recent findings on the role of the genomic integration site in determining the clonality and the potential for malignant transformation of cells carrying integrated HTLV-1 or gene therapy vectors, and how these results have contributed to the understanding of HTLV-1 pathogenesis and to improvements in gene therapy vector safety. PMID:25365582

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era

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Kimberley L. S. Ambler

2012-01-01

Full Text Available The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 109/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6% had an ITP diagnosis and platelet count <20 × 109/L. Initial ITP treatment included IVIG, n=12; steroids, n=10; anti-RhD, n=8; HAART, n=3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71% required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed.

Biochemical Manifestation of HIV Lipodystrophy Syndrome.

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Ihenetu, Kenneth; Mason, Darius

2012-01-01

Highly active anti-retroviral therapy (HAART), including protease inhibitors (PI) have led to dramatic improvements in the quality and quantity of life in patients with acquired immunodeficiency syndrome (AIDS). However, a significant number of AIDS patients on HAART develop characteristic changes in body fat redistribution referred to as lipodystrophy syndrome (LDS). Features of LDS include hypertrophy in the neck fat pad (buffalo hump), increased fat in the abdominal region (protease paunch), gynecomastia and loss of fat in the mid-face and extremities. The aim of this paper is to review the current knowledge regarding this syndrome. This article reviews the published investigations on biochemical manifestation of HIV lipodystrophy syndrome. It is estimated that approximately 64% of patients treated with PI will experience this syndrome. Biochemically, these patients have increased triglycerides (Trig), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and extremely low high-density lipoprotein-cholesterol (HDL-C). It is hoped that awareness of this syndrome would aid in early diagnosis and better patient management, possibly leading to a lower incidence of cardiovascular complications among these patients.

Potential mechanisms for cell-based gene therapy to treat HIV/AIDS

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Herrera-Carrillo, Elena; Berkhout, Ben

2015-01-01

An estimated 35 million people are infected with HIV worldwide. Anti-retroviral therapy (ART) has reduced the morbidity and mortality of HIV-infected patients but efficacy requires strict adherence and the treatment is not curative. Most importantly, the emergence of drug-resistant virus strains and

The impact of HAART on the respiratory complications of HIV infection: longitudinal trends in the MACS and WIHS cohorts.

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Matthew R Gingo

Full Text Available To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART.Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS] and women (Women's Interagency HIV Study [WIHS], followed since 1984 and 1994, respectively.Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era.Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2-2.7; p<0.001 and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3-1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8-2.7; p<0.001. Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02-8.4; p = 0.046. After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3-1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5-2.4; p<0.001.HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality.

Limits on replenishment of the resting CD4+ T cell reservoir for HIV in patients on HAART.

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Ahmad R Sedaghat

2007-08-01

Full Text Available Whereas cells productively infected with human immunodeficiency virus type 1 (HIV-1 decay rapidly in the setting of highly active antiretroviral therapy (HAART, latently infected resting CD4(+ T cells decay very slowly, persisting for the lifetime of the patient and thus forming a stable reservoir for HIV-1. It has been suggested that the stability of the latent reservoir is due to low-level viral replication that continuously replenishes the reservoir despite HAART. Here, we offer the first quantitative study to our knowledge of inflow of newly infected cells into the latent reservoir due to viral replication in the setting of HAART. We make use of a previous observation that in some patients on HAART, the residual viremia is dominated by a predominant plasma clone (PPC of HIV-1 not found in the latent reservoir. The unique sequence of the PPC serves as a functional label for new entries into the reservoir. We employ a simple mathematical model for the dynamics of the latent reservoir to constrain the inflow rate to between 0 and as few as 70 cells per day. The magnitude of the maximum daily inflow rate is small compared to the size of the latent reservoir, and therefore any inflow that occurs in patients on HAART is unlikely to significantly influence the decay rate of the reservoir. These results suggest that the stability of the latent reservoir is unlikely to arise from ongoing replication during HAART. Thus, intensification of standard HAART regimens should have minimal effects on the decay of the latent reservoir.

Breast-axillary complex in HIV/AIDS patients.

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Eni, U E; Naaya, H U; Yawe, K D T; Lawan, M A; Bakari, A A

2010-01-01

HIV/AIDS have not only increased the health care burden especially in developing countries, it equally complicates the presentation of many diseases. Some well known disease entities now occur in fulminant complexities not previously described or known as such. The objective of this article is to report an unusual presentation of HIV/AIDS patients to the surgeon with Axillary and ipsilateral breast swelling. This is a report of three cases seen and managed by the authors. Three adult female patients presented with progressively increasing axillary and ipsilateral breast swellings. They also had associated fevers and weight loss. Their main concern had been development of breast cancer. One of the patients was a known retroviral positive on Highly Active Anti-Retroviral Therapy (HAART). Examination revealed axillary abscess and ipsilateral breast oedema in two cases. The patient on HAART had a hard breast-axillary mass complex. Biopsy (FNAB) revealed inflammatory cells and no malignancy in all three cases. HIV screening was positive in all cases. One of the patients had excision of breast-axillary mass complex, and the histology showed features of chronic inflammation, with no malignant cells. The other two had incision and drainage of their axillary abscess. This shows the ubiquitous presentation of HIV/AIDS in our environment and surgeons should be aware of the breast axillary complex in HIV/AIDS. Medical practitioners should be careful to obtain accurate diagnosis before embarking on treatment especially mutilating surgical procedures.

A narrative review of cost-effectiveness analysis of people living with HIV treated with HAART: from interventions to outcomes

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Tse WF

2015-08-01

Full Text Available Wah Fung Tse,1 Weimin Yang,2 Wenlong Huang1,3 1School of International Pharmaceutical Business, China Pharmaceutical University, 2Editorial Department of Journal of Nanjing University of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, 3Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China Background: Since its introduction in 1996, highly active antiretroviral therapy (HAART, which involves the combination of antiretroviral drugs, has resulted in significant improvements in the morbidity, mortality, and life expectancy of HIV-infected patients. Numerous studies of the cost-effectiveness of HAART from different perspectives in HIV have been reported.Aim: To investigate the economic outcomes and relevance of HAART for people living with HIV.Materials and methods: A narrative literature review was conducted on 22 peer-reviewed full economic evaluations of people living with HIV treated with different HAART regimens and published in English between January 2005 and December 2014. Information regarding study details, such as interventions, outcomes, and modeling methods, was extracted. The high heterogeneity of the included studies rendered a meta-analysis inappropriate; therefore, we conducted a comparative analysis of studies grouped according to the similarity of the different intervention types and outcomes.Results: Most of the economic evaluations of HAART focused on comparisons between the specific HAART regimens and others from the following perspectives: injecting drug users versus noninjecting drug users, HIV-infected adults without AIDS versus those with AIDS, regimens based on developed world guidelines versus those based on developing world guidelines, self-administered HAART versus directly observed HAART, and “ideal” versus “typical” regimens.Conclusion: In general, HAART is more cost-effective than other therapeutic

Early initiation of highly active antiretroviral therapy fails to reverse immunovirological abnormalities in gut-associated lymphoid tissue induced by acute HIV infection.

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Tincati, Camilla; Biasin, Mara; Bandera, Alessandra; Violin, Michela; Marchetti, Giulia; Piacentini, Luca; Vago, Gian Luca; Balotta, Claudia; Moroni, Mauro; Franzetti, Fabio; Clerici, Mario; Gori, Andrea

2009-01-01

During the acute phase of HIV infection, large CD4+ T-cell depletion occurs in the gastrointestinal tract. The kinetics of CD4+ T-cell decrease and highly active antiretroviral therapy (HAART)-mediated immune reconstitution were evaluated. Rectosigmoid colonic (RSC) biopsies and blood samples of nine patients with acute HIV infection were collected. CD4+ T-cell count, HIV RNA, intracellular HIV DNA and messenger RNA cytokine expression were evaluated before and after 6 months of HAART. All nine patients presented symptomatic retroviral infection. Early HAART was associated with a sustained and comparable reduction of HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs) and RSC biopsies. HIV DNA decreased in PBMCs, but was only marginally reduced in RSC biopsies. Comparisons between reduction rates of HIV DNA in these two compartments confirmed that HIV DNA clearance was less efficient in RSC biopsies compared with PBMCs. Assessment of immunological profiles in PBMCs and RSC biopsies showed that the T-helper (Th)1-like/Th2-like ratio was sharply decreased in RSC biopsies and increased in PBMCs throughout the study period. A persistent Th2-like profile was detected in RSC biopsies. Efficient clearing of HIV DNA observed in PBMCs correlated with the establishment of a more favourable Th1-like profile. A less efficient clearance of intracellular HIV DNA following early introduction of HAART is associated with persistent immunological impairment in gut-associated lymphoid tissue (GALT), which is reflected by the skewed expression of cytokines in this reservoir. The present study shows that early initiation of HAART, in the short-term, is not effective in containing the establishment of HIV infection and in reversing associated immunological GALT abnormalities.

HIV enteropathy: HAART reduces HIV-induced stem cell hyperproliferation and crypt hypertrophy to normal in jejunal mucosa.

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Batman, Philip A; Kapembwa, Moses S; Belmonte, Liliana; Tudor, Gregory; Kotler, Donald P; Potten, Christopher S; Booth, Catherine; Cahn, Pedro; Griffin, George E

2014-01-01

To analyse the structural and kinetic response of small intestinal crypt epithelial cells including stem cells to highly active antiretroviral therapy (HAART). Crypt size and proliferative activity of transit and stem cells in jejunal mucosa were quantified using morphometric techniques. Crypt length was measured by counting the number of enterocytes along one side of a number of crypts in each biopsy specimen and the mean crypt length was calculated. Proliferating crypt cells were identified with MIB-1 monoclonal antibody, and the percentage of crypt cells in proliferation was calculated at each cell position along the length of the crypt (proliferation index). Data were obtained from 9 HIV-positive test patients co-infected with microsporidia, 34 HIV-positive patients receiving HAART and 13 control cases. Crypt length was significantly greater in test patients than in controls, but crypt length in patients receiving HAART was normal. The proliferation index was greater in test subjects than in controls in stem and transit cell compartments, and was decreased in patients treated with HAART only in the stem cell region of the crypt. Villous atrophy in HIV enteropathy is attributed to crypt hypertrophy and encroachment of crypt cells onto villi. HAART restores normal crypt structure by inhibition of HIV-driven stem cell hyperproliferation at the crypt bases.

Regressão de psoríase em paciente HIV-positivo após terapia anti-retroviral Regression of psoriasis in HIV patient after antiretroviral therapy

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Maria de Fátima Amorin Ruiz

2003-12-01

Full Text Available A síndrome da imunodeficiência adquirida foi reconhecida pela primeira vez como nova doença em 1981 devido à associação atípica de sarcoma de Kaposi e pneumonia por Pneumocystis carinii em homens. A pele é sede freqüente de doenças conseqüentes a essa infecção. A psoríase é dermatose crônica que afeta proporção que varia de 1,3 a 5% dos pacientes infectados com HIV. Portadores de psoríase que apresentem formas clínicas exacerbadas e dificuldade de resposta terapêutica devem ser investigados para possível infecção pelo HIV. É relatado caso de paciente do sexo masculino, de 44 anos, que iniciou com lesões eritêmato-escamosas no couro cabeludo, nos cotovelos, joelhos, palma das mãos, planta dos pés, além de comprometimento ungueal, após infecção pelo HIV. Confirmado o diagnóstico de psoríase e introduzida a terapia anti-retroviral, houve melhora significativa das lesões.Immunodeficiency syndrome was first described as a new disease in 1981 because an unusual association of Kaposi's Sarcoma and Pneumocystis carinii pneumonia in men. The skin is a frequent site of diseases due to this infection. Psoriasis is a chronic dermatitis that affects 1.3-5% of HIV-positive patients. The case is described of a 44-year-old man with onset of erythematous scaly lesions in scalp, elbows, knees, hands, feet and nails following HIV infection. After diagnosis of psoriasis was confirmed and antiretroviral therapy instigated, he presented improvement of the psoriasis lesions.

Unmeasured confounding caused slightly better response to HAART within than outside a randomized controlled trial

DEFF Research Database (Denmark)

Hansen, Anders Bach Bergstrøm; Gerstoft, J.; Kirk, O.

2008-01-01

OBJECTIVE: To compare the outcome of highly active antiretroviral therapy (HAART) in HIV-infected patients initiating equivalent regimens within and outside a randomized controlled trial (RCT). STUDY DESIGN AND SETTING: The Danish Protease Inhibitor Study (DAPIS) was a national multicenter RCT...

Retroviral packaging cells encapsulated in TheraCyte immunoisolation devices enable long-term in vivo gene delivery.

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Krupetsky, Anna; Parveen, Zahida; Marusich, Elena; Goodrich, Adrienne; Dornburg, Ralph

2003-05-01

The method of delivering a therapeutic gene into a patient is still one of the major obstacles towards successful human gene therapy. Here we describe a novel gene delivery approach using TheraCyte immunoisolation devices. Retroviral vector producing cells, derived from the avian retrovirus spleen necrosis virus, SNV, were encapsulated in TheraCyte devices and tested for the release of retroviral vectors. In vitro experiments show that such devices release infectious retroviral vectors into the tissue culture medium for up to 4 months. When such devices were implanted subcutaneously in SCID mice, infectious virus was released into the blood stream. There, the vectors were transported to and infected tumors, which had been induced by subcutaneous injection of tissue culture cells. Thus, this novel concept of a continuous, long-term gene delivery may constitute an attractive approach for future in vivo human gene therapy.

Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters

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Jonsson, Michele; Fusco, Jennifer S.; Cole, Stephen R.; Thomas, James C.; Porter, Kholoud; Kaufman, Jay S.; Davidian, Marie; White, Alice D.; Hartmann, Katherine E.; Eron, Joseph J.; del Amo, Julia; Meyer, Laurence; Bucher, Heiner C.; Chene, Geneviève; Pillay, Deenan; Prins, Maria; Rosinska, Magda; Sabin, Caroline; Touloumi, Giota; Lodi, Sara; Coughlin, Kate; Walker, Sarah; Babiker, Abdel; de Luca, Andrea; Fisher, Martin; Muga, Roberto; Kaldor, John; Kelleher, Tony; Ramacciotti, Tim; Gelgor, Linda; Cooper, David; Smith, Don; Gill, John; Jørgensen, Louise Bruun; Nielsen, Claus; Pedersen, Court; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Guiguet, Marguerite; Vanhems, Philippe; Chaix, Marie-Laure; Ghosn, Jade; Boufassa, Faroudy; Hamouda, Osamah; Geskus, Ronald; van der Helm, Jannie; Schuitemaker, Hanneke

2011-01-01

To estimate the clinical benefit of highly active antiretroviral therapy (HAART) initiation vs deferral in a given month in patients with CD4 cell counts less than 800/μL. In this observational cohort study of human immunodeficiency virus type 1 seroconverters from CASCADE (Concerted Action on

Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies

DEFF Research Database (Denmark)

May, M; Sterne, JAC; Sabin, C

2007-01-01

OBJECTIVE: To estimate the prognosis over 5 years of HIV-1-infected, treatment-naive patients starting HAART, taking into account the immunological and virological response to therapy. DESIGN: A collaborative analysis of data from 12 cohorts in Europe and North America on 20,379 adults who started...... of AIDS or death (death alone) from the start of HAART ranged from 5.6 to 77% (1.8-65%), depending on age, CD4 cell count, HIV-1-RNA level, clinical stage, and history of injection drug use. From 6 months the corresponding figures were 4.1-99% for AIDS or death and 1.3-96% for death alone. CONCLUSION......: On the basis of data collected routinely in HIV care, prognostic models with high discriminatory power over 5 years were developed for patients starting HAART in industrialized countries. A risk calculator that produces estimates for progression rates at years 1 to 5 after starting HAART is available from www.art-cohort-collaboration.org....

Toxic metabolic syndrome associated with HAART

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Haugaard, Steen B

2006-01-01

(HAART) may encounter the HIV-associated lipodystrophy syndrome (HALS), which attenuates patient compliance to this treatment. HALS is characterised by impaired glucose and lipid metabolism and other risk factors for cardiovascular disease. This review depicts the metabolic abnormalities associated...... with HAART by describing the key cell and organ systems that are involved, emphasising the role of insulin resistance. An opinion on the remedies available to treat the metabolic abnormalities and phenotype of HALS is provided....

Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America.

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Brenda Crabtree-Ramírez

Full Text Available Since 2009, earlier initiation of highly active antiretroviral therapy (HAART after an opportunistic infection (OI has been recommended based on lower risks of death and AIDS-related progression found in clinical trials. Delay in HAART initiation after OIs may be an important barrier for successful outcomes in patients with advanced disease. Timing of HAART initiation after an OI in "real life" settings in Latin America has not been evaluated.Patients in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet ≥18 years of age at enrolment, from 2001-2012 who had an OI before HAART initiation were included. Patients were divided in an early HAART (EH group (those initiating within 4 weeks of an OI and a delayed HAART (DH group (those initiating more than 4 weeks after an OI. All patients with an AIDS-defining OI were included. In patients with more than one OI the first event reported was considered. Calendar trends in the proportion of patients in the EH group (before and after 2009 were estimated by site and for the whole cohort. Factors associated with EH were estimated using multivariable logistic regression models.A total of 1457 patients had an OI before HAART initiation and were included in the analysis: 213 from Argentina, 686 from Brazil, 283 from Chile, 119 from Honduras and 156 from Mexico. Most prevalent OI were Tuberculosis (31%, followed by Pneumocystis pneumonia (24%, Invasive Candidiasis (16% and Toxoplasmosis (9%. Median time from OI to HAART initiation decreased significantly from 5.7 (interquartile range [IQR] 2.8-12.1 weeks before 2009 to 4.3 (IQR 2.0-7.1 after 2009 (p<0.01. Factors associated with starting HAART within 4 weeks of OI diagnosis were lower CD4 count at enrolment (p-<0.001, having a non-tuberculosis OI (p<0.001, study site (p<0.001, and more recent years of OI diagnosis (p<0.001.The time from diagnosis of an OI to HAART initiation has decreased in Latin America coinciding with the

Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients

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Ansemant Thiphaine

2013-01-01

Full Text Available Abstract Background Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy could contribute to SHD and aggravate bone catabolism in these patients. Methods A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone markers evaluations. Results Ninety-five (36% patients had SHD. In univariate analysis, a significant and positive association was found between SHD and IL6 (p = 0.001, hsCRP (p = 0.04, increased serum C-Telopeptides X (CTX (p = 0.005 and Parathyroid Hormon (PTH (p Conclusions SHD is frequent and correlates with inflammation in HIV infected patients. Since SHD is also associated with falls and increased bone catabolism, it may be of interest to take into account not only the type of antiretroviral therapy but also the residual inflammation on HAART in order to assess functional and bone risks. This finding also suggests that vitamin D supplementation may be beneficial in these HIV-infected patients.

Preventive measures to prevent loss to follow-up in highly active antiretroviral therapy (HAART): implementing a strategy in Ziguinchor (Casamance, Senegal) in 2014.

Science.gov (United States)

Randé, H; Rouffy, D

2016-05-01

Since 2010, the Pharmacie et Aide Humanitaire (PAH) in Casamance (Senegal) has been maintaining a software package (Tacojo) that allows monthly monitoring of the distribution of treatment to every patient with HIV infection receiving highly active antiretroviral therapy (HAART). We used this program to set up measures to prevent the loss to follow-up of patients receiving HAART. Our involvement focused on two main areas. First, each patient is routinely contacted after inclusion, to help us to understand the patient's experience of the disease and the treatment. This process aims to improve adherence to the treatment. Then, all patients who miss an appointment are routinely contacted by telephone within seven days of that appointment. The goal is to understand the reasons for the absence and to encourage patients to continue their treatment. Despite the lack of distance due to the relative newness of this program, these preventive measures have shown hopeful results (80% of the patients came back after a call). It would be interesting to apply it in a sustainable manner and in more medical facilities.

Characterizing retention in HAART as a recurrent event process: insights into 'cascade churn'.

Science.gov (United States)

Nosyk, Bohdan; Lourenço, Lillian; Min, Jeong Eun; Shopin, Dimitry; Lima, Viviane D; Montaner, Julio S G

2015-08-24

The benefits of HAART rely on continuous lifelong treatment retention. We used linked population-level health administrative data to characterize durations of HAART retention and nonretention. This is a retrospective cohort study. We considered individuals initiating HAART in British Columbia (1996-2012). An HAART episode was considered discontinued if individuals had a gap of at least 30 days between days in which medication was prescribed. We considered durations of HAART retention and nonretention separately, and used Cox proportional hazards frailty models to identify demographic and treatment-related factors associated with durations of HAART retention and nonretention. Six thousand one hundred fifty-two individuals were included in the analysis; 81.2% were male, 40.6% were people who inject drugs, and 42.8% initiated treatment with CD4 cell count less than 200 cells/μl. Overall, 29% were continuously retained on HAART through the end of follow-up. HAART episodes were a median 6.8 months (25th, 75th percentile: 2.3, 19.5), whereas off-HAART episodes lasted a median 1.9 months (1.2, 4.5). In Cox proportional hazards frailty models, durations of HAART retention improved over time. Successive treatment episodes tended to decrease in duration among those with multiple attempts, whereas off-HAART episodes remained relatively stable. Younger age, earlier stages of disease progression, and injection drug use were all associated with shorter durations of HAART retention and longer off-HAART durations. Metrics to monitor HAART retention, dropout, and reentry should be prioritized for HIV surveillance. Clinical strategies and public health policies are urgently needed to improve HAART retention, particularly among those at earlier stages of disease progression, the young, and people who inject drugs.

Effects of highly active antiretroviral therapy on the survival of HIV ...

African Journals Online (AJOL)

Recent improvements in access to Anti-Retroviral Therapy (ART) have radically reduced hospitalizations and deaths associated with HIV infection in both developed countries and sub-Saharan Africa. Not much is known about survival of patients on ART in slums. The objective of this study was to identify factors associated ...

Youth, unemployment, and male gender predict mortality in AIDS patients started on HAART in Nigeria.

Science.gov (United States)

DeSilva, Malini B; Merry, Stephen P; Fischer, Philip R; Rohrer, James E; Isichei, Christian O; Cha, Stephen S

2009-01-01

This retrospective study identifies risk factors for mortality in a cohort of HIV-positive adult patients treated with highly active antiretroviral therapy (HAART) in Jos, Nigeria. We analyzed clinical data from a cohort of 1552 patients enrolled in a HIV/acquired immune deficiency syndrome treatment program and started on HAART between December 2004 and 30 April 2006. Death was our study endpoint. Patients were followed in the study until death, being lost to follow-up, or the end of data collection, 1 December 2006. Baseline patient characteristics were compared using Wilcoxon Rank Sum Test for continuous variables and Pearson Chi-Square test for categorical variables to determine if certain demographic factors were associated with more rapid progression to death. The Cox proportional hazard multivariate model analysis was used to find risk factors. As of 1 December 2006, a total of 104 cases progressed to death. In addition to the expected association of CD4 count less than 50 at initiation of therapy and active tuberculosis with mortality, the patient characteristics independently associated with a more rapid progression to death after initiation of HAART were male gender, age less than 30 years old, and unemployment or unknown occupation status. Future research is needed to identify the confounding variables that may be amenable to targeted interventions aimed at ameliorating these health disparities.

Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy

Directory of Open Access Journals (Sweden)

Bacha Tigist

2012-08-01

to have treatment failure retrospectively by the authors based on their records. Hence, they were not detected and these patients were not offered second line ARTs. Conclusions Having chronic malnutrition, low CD4 at base line, chronic diarrhea after initiation of first line ART, substitution of ART drugs and age less than 3 years old were found to be independent predictors of first line ART failure in children. Most of the first line ART failure cases were not detected early and those that were detected were not switched to second line drugs in a timely fashion. Children with the above risk factors should be closely monitored for a timely switch to second line highly active anti-retroviral therapy.

Perinatal genotoxicity and carcinogenicity of anti-retroviral nucleoside analog drugs

International Nuclear Information System (INIS)

Poirier, Miriam C.; Olivero, Ofelia A.; Walker, Dale M.; Walker, Vernon E.

2004-01-01

The current worldwide spread of the human immunodeficiency virus-1 (HIV-1) to the heterosexual population has resulted in approximately 800 000 children born yearly to HIV-1-infected mothers. In the absence of anti-retroviral intervention, about 25% of the approximately 7000 children born yearly to HIV-1-infected women in the United States are HIV-1 infected. Administration of zidovudine (AZT) prophylaxis during pregnancy reduces the rate of infant HIV-1 infection to approximately 7%, and further reductions are achieved with the addition of lamivudine (3TC) in the clinical formulation Combivir. Whereas clinically this is a remarkable achievement, AZT and 3TC are DNA replication chain terminators known to induce various types of genotoxicity. Studies in rodents have demonstrated AZT-DNA incorporation, HPRT mutagenesis, telomere shortening, and tumorigenicity in organs of fetal mice exposed transplacentally to AZT. In monkeys, both AZT and 3TC become incorporated into the DNA from multiple fetal organs taken at birth after administration of human-equivalent protocols to pregnant dams during gestation, and telomere shortening has been found in monkey fetuses exposed to both drugs. In human infants, AZT-DNA and 3TC-DNA incorporation as well as HPRT and GPA mutagenesis have been documented in cord blood from infants exposed in utero to Combivir. In infants of mice, monkeys, and humans, levels of AZT-DNA incorporation were remarkably similar, and in newborn mice and humans, mutation frequencies were also very similar. Given the risk-benefit ratio, these highly successful drugs will continue to be used for prevention of vertical viral transmission, however evidence of genotoxicity in mouse and monkey models and in the infants themselves would suggest that exposed children should be followed well past adolescence for early detection of potential cancer hazard

Construction and characterization in vitro of a bicistronic retroviral vector coding endostatin and interleukin-2 for use in gene therapy; Construcao e caracterizacao in vitro de um vetor retroviral bicistronico codificando endostatina e interleucina-2 para utilizacao em terapia genica

Energy Technology Data Exchange (ETDEWEB)

Calvo, Fernanda Bernardes

2009-07-01

Gene therapy has been used in preclinical studies and clinical trials in order to alleviate or cure a disease. Retroviral vectors are a tool for gene transfer is widely used. Bicistronic vectors are an attractive alternative for treatment of complex diseases. A variety of options exists to simultaneously express two genes in genetically modified cells. The most common approach relies on bicistronic vectors in which the genes are linked to each other by an internal ribosome entry site allowing co-translational expression of both cistrons. Endostatin, the C-terminal fragment of collagen XVIII, is a potent angiogenesis inhibitor. At present, ES has been widely used in anti-angiogenic in a variety of experimental tumor models, and clinical trials to test it as an anti-tumor agent are already under way. Immunotherapy has been used as adjuvant treatment for tumors and has been used in several preclinical studies and clinical trials. The objective of this project was to construct and characterize 'in vitro' an IRES-based bicistronic retroviral vector encoding endostatin and interleukin-2. The construction of the vector was performed in three stages, the final construction was analyzed by restriction analysis and sequencing. Packaging cells were prepared. The endostatin and interleukin-2 levels were determined by Dot blot. Monocistronic and bicistronic mRNA expression were analyzed by real time RT-PCR. Bicistronic vector showed high levels of virus trites, ranging from 4.20x10{sup 5} to 1.53x10{sup 6}UFC/ml. Secreted levels of endostatin and interleukin-2 ranged from 1.08 to 2.08{mu}g/10{sup 6}cells.24h and 0.66 - 0.89{mu}g/10{sup 6}cells.24h, respectively. The mRNA expression of ES in the NIH3T3 clone pLend-IRES-IL2SN was 2 times higher than the level presented by the NIH3T3 clone pLendSN. The endostatin promoted inhibition (40%) of endothelial cell proliferation. Interleukin-2 promoted a proliferation of 10.6% lymphocytes CD4 and 8.9% of CD8. We conclude that

Strategies to Promote Adherence to Antiretroviral Therapy Applied by Dutch HIV Nurse Consultants : A Descriptive Qualitative Study

NARCIS (Netherlands)

Vervoort, Sigrid C. J. M.; Grypdonck, Mieke H. F.; Dijkstra, Boukje M.; Hazelzet, Esther E. B.; Fledderus, Bert; Borleffs, Jan C. C.; Hoepelman, Andy I. M.

2010-01-01

This study describes strategies used by Dutch HIV nurse consultants to promote adherence to anti retroviral therapy (ART) and the assumptions on which these strategies were based. The study used a descriptive qualitative design with individual and focus group interviews. Individual semi-structured

Characterizing retention in HAART as a recurrent event process: insights into ‘cascade churn’

Science.gov (United States)

Nosyk, Bohdan; Lourenço, Lillian; Min, Jeong Eun; Shopin, Dimitry; Lima, Viviane D.; Montaner, Julio S.G.

2015-01-01

Objective The benefits of HAART rely on continuous lifelong treatment retention. We used linked population-level health administrative data to characterize durations of HAART retention and nonretention. Design This is a retrospective cohort study. Methods We considered individuals initiating HAART in British Columbia (1996–2012). An HAART episode was considered discontinued if individuals had a gap of at least 30 days between days in which medication was prescribed. We considered durations of HAART retention and nonretention separately, and used Cox proportional hazards frailty models to identify demographic and treatment-related factors associated with durations of HAART retention and nonretention. Results Six thousand one hundred fifty-two individuals were included in the analysis; 81.2% were male, 40.6% were people who inject drugs, and 42.8% initiated treatment with CD4 cell count less than 200 cells/μl. Overall, 29% were continuously retained on HAART through the end of follow-up. HAART episodes were a median 6.8 months (25th, 75th percentile: 2.3, 19.5), whereas off-HAART episodes lasted a median 1.9 months (1.2, 4.5). In Cox proportional hazards frailty models, durations of HAART retention improved over time. Successive treatment episodes tended to decrease in duration among those with multiple attempts, whereas off-HAART episodes remained relatively stable. Younger age, earlier stages of disease progression, and injection drug use were all associated with shorter durations of HAART retention and longer off-HAART durations. Conclusion Metrics to monitor HAART retention, dropout, and reentry should be prioritized for HIV surveillance. Clinical strategies and public health policies are urgently needed to improve HAART retention, particularly among those at earlier stages of disease progression, the young, and people who inject drugs. PMID:26372279

Applying the theory of planned behavior to explore HAART adherence among HIV-positive immigrant Latinos: elicitation interview results.

Science.gov (United States)

Vissman, Aaron T; Hergenrather, Kenneth C; Rojas, Gabriela; Langdon, Sarah E; Wilkin, Aimee M; Rhodes, Scott D

2011-12-01

This study explored influences on intention to adhere to highly active antiretroviral therapy (HAART) among immigrant Latinos living with HIV/AIDS in the southeastern USA. Our community-based participatory research (CBPR) partnership completed individual in-depth interviews with 25 immigrant Latinos, based on the theory of planned behavior (TPB), to explore beliefs toward HAART adherence and HIV testing. Participants identified (a) seven outcomes of treatment adherence (e.g., "feeling good" and "controlling the virus"), (b) six groups of persons influencing adherence (e.g., family, partner/spouse), and (c) nine impediments to adherence (e.g., appointment scheduling, side effects of treatment). Fear of deportation, perceived costs of services, and barriers to communication emerged as impediments to both HAART adherence and HIV testing. The findings suggest the utility of TPB in identifying factors to enhance HAART adherence among immigrant Latinos. Future research should explore the extent to which these identified TPB components quantitatively influence adherence intention and immunological and virological outcomes. Culturally congruent interventions for immigrant Latinos may need to focus on facilitators of adherence, influential referent groups, and destigmatizing HIV/AIDS. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Disclosure, stigma of HIV positive child and access to early infant diagnosis in the rural communities of OR Tambo District, South Africa: a qualitative exploration of maternal perspective.

Science.gov (United States)

Adeniyi, Vincent Oladele; Thomson, Elza; Ter Goon, Daniel; Ajayi, Idowu Anthony

2015-08-26

Despite the overwhelming evidence confirming the morbidity and mortality benefits of early initiation of highly active anti-retroviral therapy (HAART) in HIV-infected infants, some children are still disadvantaged from gaining access to care. The understanding of the maternal perspective on early infant HIV diagnosis and prompt initiation of HAART has not been adequately explored, especially in the rural communities of South Africa. This study explores the perspectives of mothers of HIV-exposed infants with regard to early infant diagnosis (EID) through a lens of social and structural barriers to accessing primary healthcare in OR Tambo district, Eastern Cape Province, South Africa. In this qualitative study, we conducted semi-structured interviews at two primary healthcare centres in the King Sabata Dalindyebo Municipality of the OR Tambo district, South Africa. Twenty-four purposive sample of mothers of HIV-exposed infants took part in the study. Interviews were tape-recorded, transcribed and field notes were obtained. The findings were triangulated with two focus group discussions in order to enrich and validate the qualitative data. Thematic content analysis was employed to analyse the data. The participants have fairly good knowledge of mother-to-child transmission of HIV and the risks during pregnancy, delivery and breastfeeding. The majority of participants were confident of the protection offered by anti-retroviral drugs provided during pregnancy, however, lack knowledge of optimal time for early infant diagnosis of HIV. Reasons for not accessing EID included fear of finding out that their child is HIV positive, feelings of guilt and/or shame and embarrassment with respect to raising an HIV infected infant. Personal experiences of HIV diagnosis and HAART were associated with participants' attitudes and beliefs toward care-seeking behaviours. Stigma resulting from their own disclosure to others reduced their likelihood of recommending EID to other members of

Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers.

Science.gov (United States)

Nair, Madhavan; Guduru, Rakesh; Liang, Ping; Hong, Jeongmin; Sagar, Vidya; Khizroev, Sakhrat

2013-01-01

Although highly active anti-retroviral therapy has resulted in remarkable decline in the morbidity and mortality in AIDS patients, inadequately low delivery of anti-retroviral drugs across the blood-brain barrier results in virus persistence. The capability of high-efficacy-targeted drug delivery and on-demand release remains a formidable task. Here we report an in vitro study to demonstrate the on-demand release of azidothymidine 5'-triphosphate, an anti-human immunodeficiency virus drug, from 30 nm CoFe2O4@BaTiO3 magneto-electric nanoparticles by applying a low alternating current magnetic field. Magneto-electric nanoparticles as field-controlled drug carriers offer a unique capability of field-triggered release after crossing the blood-brain barrier. Owing to the intrinsic magnetoelectricity, these nanoparticles can couple external magnetic fields with the electric forces in drug-carrier bonds to enable remotely controlled delivery without exploiting heat. Functional and structural integrity of the drug after the release was confirmed in in vitro experiments with human immunodeficiency virus-infected cells and through atomic force microscopy, spectrophotometry, Fourier transform infrared and mass spectrometry studies.

Weight Gain and Hair Loss during Anti-TNF Therapy

Directory of Open Access Journals (Sweden)

Abdo Lutf

2012-01-01

Full Text Available Objectives. To investigate the incidence of weight gain and hair loss as adverse effects of anti-TNF therapy in rheumatic diseases. Methods. Patients using anti-TNF therapy, who are followed in rheumatology clinic, were interviewed using a questionnaire to investigate the side effects of anti-TNF therapy. Patients who complained of hair loss and weight gain were asked additional questions concerning the relationship of these adverse effects to anti-TNF use, whether therapy was stopped because of these adverse effects and if the adverse effects reversed after stopping therapy. The files were reviewed to follow the weight change before, during, and after discontinuation of anti-TNF. Results. One hundred fifty consecutive patients (82 RA, 34 ankylosing spondylitis, 32 psoriatic arthritis, and 4 for other indications were interviewed .Weight gain was observed in 20 patients (13.3% with average gain of 5.5 Kg. Anti-TNF was stopped in five patients because of this adverse effect. Hair loss during anti-TNf therapy was reported in five females (3.3% and anti-TNF therapy was stopped in all of them. Conclusion. Weight gain and hair loss appear to be associated with anti-TNF therapy and may be one reason for discontinuing the therapy.

Placebo HAART Regimen as a Method for Teaching Medication Adherence Issues to Students

OpenAIRE

Sutton, Eliza L; Transue, Emily R; Comes E, Susan; Paauw, Douglas S

2005-01-01

Placebo medication regimens may help educate students about adherence issues. In this randomized trial, 23 third-year medical students took a 2-week placebo regimen mimicking highly active antiretroviral therapy (HAART) during their medicine clerkship; 15 students served as controls. Although no effect was demonstrated from this intervention on an evaluation instrument examining attitudes and beliefs about medication nonadherence, all 23 student-subjects agreed in postintervention interviews ...

Treatment of Recurrent Hepatocellular Carcinoma with Sorafenib in a HIV/HCV Co-Infected patient in HAART: A Case Report

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De Nardo Pasquale

2012-06-01

Full Text Available Abstract Background Liver disease is the second cause of death among HIV patients receiving highly active antiretroviral therapy (HAART in Europe. HIV patients have a high prevalence of chronic HBV (6–10% and HCV (33% co-infection, and accelerated progression of viral hepatitis. Furthermore, the long duration of both HIV and HCV diseases in the HAART era increases the risk of hepatocellular carcinoma. Findings We report the case of a 49 year -old HIV/HCV co-infected male patient who developed hepatocellular carcinoma. The patient underwent a partial hepatectomy, and a few months later was treated with transcatheter arterial chemoembolisation due to hepatocarcinoma recurrence. Two months later, advanced hepatocellular carcinoma was diagnosed and sorafenib therapy was initiated. The patient achieved partial response of the main lesions, complete regression of the smallest lesions and did not experience clinical progression during the 20-month follow-up period. During therapy with sorafenib, the patient was treated with HAART with good viral and immunological responses. We used the therapeutic drug monitoring to assess antiretroviral concentrations during co-administration of sorafenib. Fosamprenavir Ctrough was found under the minimum level recommended by international guidelines. No grade 3 or 4 toxicities were observed. At month 20 of treatment, new liver lesions with portal vein thrombosis were diagnosed. After 28 months of sorafenib therapy, the patient deceased for severe liver insufficiency. Conclusions Sorafenib monotherapy demonstrated a marked delay in HCC disease progression in an HIV/HCV co-infected patient. Fosamprenavir Ctrough was found under the minimum level recommended by international guidelines, suggesting a possible interaction.

Removal of envelope protein-free retroviral vectors by anion-exchange chromatography to improve product quality.

Science.gov (United States)

Rodrigues, Teresa; Alves, Ana; Lopes, António; Carrondo, Manuel J T; Alves, Paula M; Cruz, Pedro E

2008-10-01

We have investigated the role of the retroviral lipid bilayer and envelope proteins in the adsorption of retroviral vectors (RVs) to a Fractogel DEAE matrix. Intact RVs and their degradation components (envelope protein-free vectors and solubilized vector components) were adsorbed to this matrix and eluted using a linear gradient. Envelope protein-free RVs (Env(-)) and soluble envelope proteins (gp70) eluted in a significantly lower range of conductivities than intact RVs (Env(+)) (13.7-30 mS/cm for Env(-) and gp70 proteins vs. 47-80 mS/cm for Env(+)). The zeta (zeta)-potential of Env(+) and Env(-) vectors was evaluated showing that envelope proteins define the pI of the viral particles (pI (Env(+)) improvement to the quality of retroviral preparations for gene therapy applications.

Retroviral-mediated gene therapy for the differentiation of primary cells into a mineralizing osteoblastic phenotype.

Science.gov (United States)

Phillips, Jennifer E; García, Andrés J

2008-01-01

Bone tissue engineering has emerged as a promising strategy for the repair of critical-sized skeletal fractures. However, the clinical application of this approach has been limited by the availability of a robust mineralizing cell source. Non-osteogenic cells, such as skin fibroblasts, are an attractive cell-source alternative because they are easy to harvest from autologous donor skin biopsies and display a high capacity for in vitro expansion. We have recently demonstrated that retroviral gene delivery of the osteoblastic transcription factor Runx2/Cbfa1 promotes osteogenic differentiation in primary dermal fibroblasts cultured in monolayer. Notably, sustained expression of Runx2 was not sufficient to promote functional osteogenesis in these cells, and co-treatment with the steroid hormone dexamethasone was required to induce deposition of biologically-equivalent matrix mineralization. On the basis of these results, we then investigated the osteogenic capacity of these genetically engineered fibroblasts when seeded on polymeric scaffolds in vitro and in vivo. These experiments demonstrated that Runx2-expressing fibroblasts seeded on collagen scaffolds produce significant levels of matrix mineralization after 28 days in vivo implantation in a subcutaneous, heterotopic site. Overall, these results offer evidence that transcription factor-based gene therapy may be a powerful strategy for the conversion of a non-osteogenic cellular phenotype into a mineralizing cell source for bone repair applications. This concept may also be applied to control functional differentiation in a broad range of cell types and tissue engineering applications. The chapter below outlines detailed methods for the isolation and ex vivo genetic modification of primary dermal fibroblasts using retroviral-mediated delivery of the Runx2 transgene in both monolayer culture and three-dimensional scaffolds.

German-austrian recommendations for HIV1-therapy in pregnancy and in HIV1-exposed newborn - update 2008

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Buchholz Bernd

2009-11-01

Full Text Available Abstract German-Austrian recommendations for HIV1-therapy in pregnancy - Update 2008 Bernd Buchholz (University Medical Centre Mannheim, Pediatric Clinic, Matthias Beichert (Mannheim, Gynecology and Obstetrics Practice, Ulrich Marcus (Robert Koch Institute, Berlin, Thomas Grubert, Andrea Gingelmaier (Gynecology Clinic of the Ludwig Maximilians University of Munich, Dr. med. Annette Haberl (HIV-Department, J. W. Goethe-University Hospital, Frankfurt, Dr. med. Brigitte Schmied (Otto-Wagner Spital, Wien. In Germany during the last years about 200-250 HIV1-infected pregnant women delivered a baby each year, a number that is currently increasing. To determine the HIV-status early in pregnancy voluntary HIV-testing of all pregnant women is recommended in Germany and Austria as part of prenatal care. In those cases, where HIV1-infection was known during pregnancy, since 1995 the rate of vertical transmission of HIV1 was reduced to 1-2%. This low transmission rate has been achieved by the combination of anti-retroviral therapy of pregnant women, caesarean section scheduled before onset of labour, anti-retroviral post exposition prophylaxis in the newborn and refraining from breast-feeding by the HIV1-infected mother. To keep pace with new results in research, approval of new anti-retroviral drugs and changes in the general treatment recommendations for HIV1-infected adults, in 1998, 2001, 2003 and 2005 an interdisciplinary consensus meeting was held. Gynaecologists, infectious disease specialists, paediatricians, pharmacologists, virologists and members of the German AIDS Hilfe (NGO were participating in this conference to update the prevention strategies. A fifth update became necessary in 2008. The updating process was started in January 2008 and was terminated in September 2008. The guidelines provide new recommendations on the indication and the starting point for HIV-therapy in pregnancies without complications, drugs and drug combinations to be

T-cell mean telomere lengths changes in treatment naïve HIV-infected patients randomized to G-CSF or placebo simultaneously with initiation of HAART

DEFF Research Database (Denmark)

Aladdin, H; Von Essen, M; Schjerling, P

2001-01-01

The effect of highly active antiretroviral therapy (HAART) and granulocyte colony stimulating factor (G-CSF) on mean telomere restriction fragment (TRF) length of peripheral blood mononuclear cells (PBMC) was examined in 11 treatment naïve human immunodeficiency virus (HIV)-infected individuals...... with a CD4+ T-cell count CSF thrice weekly for 12 weeks (n = 6) or placebo (n = 5). An increase in the mean TRF lengths was observed in PBMC of patients on HAART after 24 weeks of treatment mainly owing to increased mean CD8+ T-cell TRF...... lengths. However, in the group of patients on HAART combined with G-CSF no changes of PBMC mean TRF length was observed during treatment or during 12 weeks of follow-up. The mean CD4+ T-cell TRF length did not change in any of the two groups. These results confirm that HAART induces mainly the lengthening...

Risk of melanoma in people with HIV/AIDS in the pre- and post-HAART eras: a systematic review and meta-analysis of cohort studies.

Science.gov (United States)

Olsen, Catherine M; Knight, Lani L; Green, Adèle C

2014-01-01

Following the introduction of highly active antiretroviral therapy (HAART) the risk of AIDS-defining cancers decreased but incidence of many non-AIDS-defining cancers has reportedly increased in those with HIV/AIDS. Whether melanoma risk has also changed in HIV/AIDS patients post-HAART is unknown and therefore we evaluated this in comparison with the risk before HAART. Systematic review and meta-analysis. We searched Medline, Embase and ISI science citation index databases to April 2013. All cohort studies of patients diagnosed with HIV/AIDS that permitted quantitative assessment of the association with melanoma were eligible. Detailed quality assessment of eligible studies was conducted, focussing particularly on adjustment for ethnicity, a priori considered essential for an unbiased assessment of melanoma risk. Data were pooled using a random effects model. From 288 articles, we identified 21 that met the inclusion criteria, 13 presenting data for the post-HAART era and 8 for the pre-HAART era. Post-HAART the pooled relative risk (pRR) for the association between HIV/AIDS and melanoma was 1.26 (95% CI, 0.97-1.64) and 1.50 (95% CI 1.12-2.01) among studies that accounted for ethnicity, with evidence of significant heterogeneity (P = 0.004, I2 = 55.5). Pre-HAART pRRs were 1.26 (95% CI 1.11-1.43; P het = 0.82) and 1.28 (95% CI 1.10-1.49) among studies adjusted for ethnicity. People with HIV/AIDS remain at a significantly increased risk of developing melanoma in the post-HAART era. White skinned people with HIV/AIDS should be screened regularly and counselled against excessive sun exposure.

Adeno-associated virus Rep-mediated targeting of integrase-defective retroviral vector DNA circles into human chromosome 19

International Nuclear Information System (INIS)

Huang, Shuohao; Kawabe, Yoshinori; Ito, Akira; Kamihira, Masamichi

2012-01-01

Highlights: ► Adeno-associated virus (AAV) is capable of targeted integration in human cells. ► Integrase-defective retroviral vector (IDRV) enables a circular DNA delivery. ► A targeted integration system of IDRV DNA using the AAV integration mechanism. ► Targeted IDRV integration ameliorates the safety concerns for retroviral vectors. -- Abstract: Retroviral vectors have been employed in clinical trials for gene therapy owing to their relative large packaging capacity, alterable cell tropism, and chromosomal integration for stable transgene expression. However, uncontrollable integrations of transgenes are likely to cause safety issues, such as insertional mutagenesis. A targeted transgene integration system for retroviral vectors, therefore, is a straightforward way to address the insertional mutagenesis issue. Adeno-associated virus (AAV) is the only known virus capable of targeted integration in human cells. In the presence of AAV Rep proteins, plasmids possessing the p5 integration efficiency element (p5IEE) can be integrated into the AAV integration site (AAVS1) in the human genome. In this report, we describe a system that can target the circular DNA derived from non-integrating retroviral vectors to the AAVS1 site by utilizing the Rep/p5IEE integration mechanism. Our results showed that after G418 selection 30% of collected clones had retroviral DNA targeted at the AAVS1 site.

New windows into retroviral RNA structures.

Science.gov (United States)

Jayaraman, Dhivya; Kenyon, Julia Claire

2018-01-25

The multiple roles of both viral and cellular RNAs have become increasingly apparent in recent years, and techniques to model them have become significantly more powerful, enabling faster and more accurate visualization of RNA structures. Techniques such as SHAPE (selective 2'OH acylation analysed by primer extension) have revolutionized the field, and have been used to examine RNAs belonging to many and diverse retroviruses. Secondary structure probing reagents such as these have been aided by the development of faster methods of analysis either via capillary or next-generation sequencing, allowing the analysis of entire genomes, and of retroviral RNA structures within virions. Techniques to model the three-dimensional structures of these large RNAs have also recently developed. The flexibility of retroviral RNAs, both structural and functional, is clear from the results of these new experimental techniques. Retroviral RNA structures and structural changes control many stages of the lifecycle, and both the RNA structures themselves and their interactions with ligands are potential new drug targets. In addition, our growing understanding of retroviral RNA structures is aiding our knowledge of cellular RNA form and function.

Cross-packaging of genetically distinct mouse and primate retroviral RNAs

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Jaballah Soumeya

2009-07-01

Full Text Available Abstract Background The mouse mammary tumor virus (MMTV is unique from other retroviruses in having multiple viral promoters, which can be regulated by hormones in a tissue specific manner. This unique property has lead to increased interest in studying MMTV replication with the hope of developing MMTV based vectors for human gene therapy. However, it has recently been reported that related as well as unrelated retroviruses can cross-package each other's genome raising safety concerns towards the use of candidate retroviral vectors for human gene therapy. Therefore, using a trans complementation assay, we looked at the ability of MMTV RNA to be cross-packaged and propagated by an unrelated primate Mason-Pfizer monkey virus (MPMV that has intracellular assembly process similar to that of MMTV. Results Our results revealed that MMTV and MPMV RNAs could be cross-packaged by the heterologous virus particles reciprocally suggesting that pseudotyping between two genetically distinct retroviruses can take place at the RNA level. However, the cross-packaged RNAs could not be propagated further indicating a block at post-packaging events in the retroviral life cycle. To further confirm that the specificity of cross-packaging was conferred by the packaging sequences (ψ, we cloned the packaging sequences of these viruses on expression plasmids that generated non-viral RNAs. Test of these non-viral RNAs confirmed that the reciprocal cross-packaging was primarily due to the recognition of ψ by the heterologous virus proteins. Conclusion The results presented in this study strongly argue that MPMV and MMTV are promiscuous in their ability to cross-package each other's genome suggesting potential RNA-protein interactions among divergent retroviral RNAs proposing that these interactions are more complicated than originally thought. Furthermore, these observations raise the possibility that MMTV and MPMV genomes could also co-package providing substrates for

Systemic Effects of Anti-Angiogenic Therapy

International Nuclear Information System (INIS)

Starlinger, P.

2011-01-01

Anti-angiogenic cancer therapy has gained importance within the past decades. In this context, Bevacizumab, a monoclonal antibody neutralizing vascular endothelial growth factor, has been approved for clinical use. The combination of chemotherapy with Bevacizumab has shown a remarkable benefit in several neoplastic entities. However, a notable number of patients do not respond to this therapy. Furthermore, response to therapy seems to be short-lived. The primary topic of this PhD thesis was to characterize systemic effects of anti-angiogenic therapy to possibly identify mechanisms that could explain this heterogeneity in therapy response. To this end, a carefully selected subset of angiogenesis factors were monitored in detail in the course of a clinical study of pancreatic cancer receiving gemcitabine based anti-angiogenic therapy with Bevacizumab. To enable the reliable monitoring of angiogenesis parameters, we initially defined an optimized procedure to evaluate angiogenesis factors in blood. During these investigations a remarkable association of circulating angiogenic growth factors with platelet counts and activation was observed. Strikingly, we were able to confirm this association in the clinical setting. In particular, the anti-angiogenic factor thrombospondin-1 (TSP-1) correlated with platelet counts. We further showed that the highly myelosuppressive chemotherapeutic agent gemcitabine resulted in a decrease of platelet counts and circulating TSP-1 levels. As a result, we hypothesized that the choice of chemotherapy might affect the angiogenic balance and counteract the therapeutic effect of bevacizumab. This notion was further supported by a careful evaluation of other studies reporting on the combination of Bevacizumab with thrombocytopenic chemotherapies which were generally of minor therapeutic benefit for cancer patients. To further focus on TSP-1 as an essential modulator of neovascularization and anti-angiogenic therapy we investigated TSP-1

Impact of a psychoeducative intervention on adherence to HAART among low-literacy patients in a resource-limited setting: the case of an Arab country--Morocco.

Science.gov (United States)

Khachani, Imane; Harmouche, Hicham; Ammouri, Wafa; Rhoufrani, Fatima; Zerouali, Latifa; Abouqal, Redouane; Tazi-Mezalek, Zoubida; Adnaoui, Mohamed; Aouni, Mohamed; Maouni, Abdelaziz

2012-01-01

Research has demonstrated that strict adherence is necessary to maximize highly active antiretroviral therapy (HAART) benefits. This is particularly challenging for low-literacy populations in resource-limited settings like Morocco and motivated the implementation of a psychoeducative program for patients under HAART at Rabat University Hospital. The study aimed at assessing the program's impact on adherence to antiretroviral medication, knowledge of HIV/AIDS and HAART, quality of life, and biological parameters. It included patients under treatment for at least 2 months that benefited from 3 to 5 educational and psychological support sessions. Data were collected at baseline, 3 and 6 months. In all, 50 patients were included. The mean age was 38 years; 52% were illiterate and 62% unemployed. Adherence scores were high at baseline (98%) and showed no significant change throughout the study. Knowledge of HAART and HIV/AIDS, and quality of life improved significantly both at months 3 and 6. Significant increase for CD4 count rates and decrease for viral load rates were also reported. The program had no significant impact on adherence but substantively developed patients' knowledge of HIV/AIDS and HAART and improved their quality of life.

Decreasing trends in hospitalizations during anti-TNF therapy are associated with time to anti-TNF therapy: Results from two referral centres.

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Mandel, Michael D; Balint, Anita; Golovics, Petra A; Vegh, Zsuzsanna; Mohas, Anna; Szilagyi, Blanka; Szabo, Agnes; Kurti, Zsuzsanna; Kiss, Lajos S; Lovasz, Barbara D; Gecse, Krisztina B; Farkas, Klaudia; Molnar, Tamas; Lakatos, Peter L

2014-11-01

Hospitalization is an important outcome measure and a major driver of costs in patients with inflammatory bowel disease. We analysed medical and surgical hospitalization rates and predictors of hospitalization before and during anti-TNF therapy. Data from 194 consecutive patients were analysed retrospectively (males, 45.4%, median age at diagnosis, 24.0 years, infliximab/adalimumab: 144/50) in whom anti-TNF therapy was started after January 1, 2008. Total follow-up was 1874 patient-years and 474 patient-years with anti-TNF exposure. Hospitalization rates hospitalization decreased only in Crohn's disease (odds ratio: 0.59, 95% confidence interval: 0.51-0.70, median 2-years' anti-TNF exposure) with a same trend for surgical interventions (p=0.07), but not in ulcerative colitis. Need for hospitalization decreased in Crohn's disease with early (within 3-years from diagnosis, p=0.016 by McNemar test), but not late anti-TNF exposure. At logistic regression analysis complicated disease behaviour (p=0.03), concomitant azathioprine (p=0.02) use, but not anti-TNF type, gender, perianal disease or previous surgeries were associated with the risk of hospitalization during anti-TNF therapy. Hospitalization rate decreased significantly in patients with Crohn's disease but not ulcerative colitis after the introduction of anti-TNF therapy and was associated with time to therapy. Complicated disease phenotype and concomitant azathioprine use were additional factors defining the risk of hospitalization. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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

Pronounced lipoatrophy in HIV-infected men receiving HAART for more than 6 years compared with the background population

DEFF Research Database (Denmark)

Hansen, AB; Lindegaard, B; Obel, N

2006-01-01

OBJECTIVES: To establish the prevalence and quantify the severity of body fat redistribution and dyslipidaemia in HIV-infected men after long-term highly active antiretroviral therapy (HAART) compared with the background population. METHODS: In a cross-sectional study, we included 87 HIV......-infected men who had received HAART for at least 6 years and 34 HIV-negative men. Regional body composition was assessed using dual-energy X-ray absorptiometry. Fasting metabolic parameters were obtained. Associations between regional body fat distribution and metabolic parameters were evaluated. RESULTS: HIV......-infected patients and controls did not differ with regard to height and lean body mass. Compared with controls, HIV-infected men had reduced total fat mass (median 12.3 versus 19.2 kg, P

HIV-Associated Burkitt Lymphoma: Good Efficacy and Tolerance of Intensive Chemotherapy Including CODOX-M/IVAC with or without Rituximab in the HAART Era

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J. A. Rodrigo

2012-01-01

Full Text Available Background. The outcome of HIV-associated non-Hodgkin lymphoma (NHL has improved substantially in the highly active antiretroviral therapy (HAART era. However, HIV-Burkitt lymphoma (BL, which accounts for up to 20% of HIV-NHL, has poor outcome with standard chemotherapy. Patients and Methods. We retrospectively reviewed HIV-BL treated in the HAART era with the Magrath regimen (CODOX-M/IVAC±R at four Canadian centres. Results. Fourteen patients with HIV-BL received at least one CODOX-M/IVAC±R treatment. Median age at BL diagnosis was 45.5 years, CD4 count 375 cells/mL and HIV viral load (VL 250 cells/mL and undetectable, respectively, in 4. Conclusion. Intensive chemotherapy with CODOX-M/IVAC±R yielded acceptable toxicity and good survival rates in patients with HIV-associated Burkitt lymphoma receiving HAART.

HIV-Associated Burkitt Lymphoma: Good Efficacy and Tolerance of Intensive Chemotherapy Including CODOX-M/IVAC with or without Rituximab in the HAART Era

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Rodrigo, J. A.; Hicks, L. K.; Cheung, M. C.; Song, K. W.; Ezzat, H.; Leger, C. S.; Boro, J.; Montaner, J. S. G.; Harris, M.; Leitch, H. A.

2012-01-01

Background. The outcome of HIV-associated non-Hodgkin lymphoma (NHL) has improved substantially in the highly active antiretroviral therapy (HAART) era. However, HIV-Burkitt lymphoma (BL), which accounts for up to 20% of HIV-NHL, has poor outcome with standard chemotherapy. Patients and Methods. We retrospectively reviewed HIV-BL treated in the HAART era with the Magrath regimen (CODOX-M/IVAC±R) at four Canadian centres. Results. Fourteen patients with HIV-BL received at least one CODOX-M/IVAC±R treatment. Median age at BL diagnosis was 45.5 years, CD4 count 375 cells/mL and HIV viral load (VL) 250 cells/mL and undetectable, respectively, in 4. Conclusion. Intensive chemotherapy with CODOX-M/IVAC±R yielded acceptable toxicity and good survival rates in patients with HIV-associated Burkitt lymphoma receiving HAART. PMID:22190945

Comparison of anti-retroviral therapy treatment strategies in prevention of mother-to-child transmission in a teaching hospital in Ethiopia.

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Kumela, Kabaye; Amenu, Demisew; Chelkeba, Legese

2015-01-01

More than 90% of Human immunodeficiency virus (HIV) infection in children is acquired due to mother-to-child transmission, which is spreading during pregnancy, delivery or breastfeeding. To determine the effectiveness of highly active antiretroviral and short course antiretroviral regimens in prevention of mother-to-child transmission of HIV and associated factors Jimma University Specialized Hospital (JUSH). A hospital based retrospective cohort study was conducted on HIV infected pregnant mothers who gave birth and had follow up at anti-retroviral therapy (ART) clinic for at least 6 months during a time period paired with their infants. The primary and secondary outcomes were rate of infant infection by HIV at 6 weeks and 6 months respectively. The Chi-square was used for the comparison of categorical data multivariate logistic regression model was used to identify the determinants of early mother-to-child transmission of HIV at 6 weeks. Cox proportional hazard model was used to analyze factors that affect the 6 month HIV free survival of infants born to HIV infected mothers. A total of 180 mother infant pairs were considered for the final analysis, 90(50%) mothers received single dose nevirapine (sdNVP) designated as regimen-3, 67 (37.2%) mothers were on different types of ARV regimens commonly AZT + 3TC + NVP (regimen-1), while the rest 23 (12.8%) mothers were on short course dual regimen AZT + 3TC + sdNVP (regimen-2). Early mother-to-child transmission rate at 6 weeks for regimens 1, 2 and 3 were 5.9% (4/67), 8.6% (2/23), and 15.5% (14/90) respectively. The late cumulative mother-to-child transmission rate of HIV at 6 months regardless of regimen type was 15.5% (28/180). Postnatal transmission at 6 months was 28.5% (8/28) of infected children. Factors that were found to be associated with high risk of early mother-to-child transmission of HIV include duration of ARV regimen shorter than 2 months during pregnancy (OR=4.3, 95%CI =1.38-13.46), base line CD4 less

Antiretroviral changes during the first year of therapy

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Antonio Carlos Policarpo Carmo Sá Bandeira

Full Text Available Summary Introduction: The Brazilian HIV/AIDS management and treatment guideline (PCDT, published in 2013, recommends and standardizes the use of highly active antiretroviral therapy (HAART in all adult patients, in spite of LTCD4 count. This study aimed to analyze the first year of HAART use in patients from a reference center on HIV/AIDS management in Fortaleza, Ceará. Method: This descriptive study reviewed all prescription forms of antiretroviral regimens initiation and changes from January to July 2014. All antiretroviral regimen changes that occurred during the first year of therapy were evaluated. Data were analyzed with SPSS version 20. Mean, standard deviation and frequency, Student’s t and Mann-Whitney tests calculations were used, with significance at p<0.05. Results: From 527 patients initiating HAART, 16.5% (n=87 had a regimen change in the first year. These patients were mostly male (59.8%; n=52, aged 20 to 39 years, with only one HAART change (72.4%; n=63. Efavirenz was the most often changed drug, followed by tenofovir, zidovudine and lopinavir/ritonavir. Mean time of HAART changes was 120 days, with adverse reactions as the most prevalent cause. HAART was effective in decreasing viral load since second month of treatment (p=0.003 and increasing LTCD4 lymphocytes since fifth month (p<0.001. Conclusion: The main cause of initial HAART changes was adverse reaction and most patients had only one change in the HAART regimen. HAART prescription was in accordance to the PCDT from 2013.

cd4 changes in haart-naïve hiv positive pregnant women on haart

African Journals Online (AJOL)

boaz

This study thus attempt an assessment of the pattern of immunologic (CD4) changes in naïve. HIV positive pregnant women, in the first two months of commencing HAART, with a view to possibly postulate CD4 response rate and recommend the ideal time to initiate HAARTin HIV positive pregnant patients. METHODOLOGY.

Liver ultrastructural morphology and mitochondrial DNA levels in HIV/hepatitis C virus coinfection: no evidence of mitochondrial damage with highly active antiretroviral therapy.

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Matsukura, Motoi; Chu, Fanny F S; Au, May; Lu, Helen; Chen, Jennifer; Rietkerk, Sonja; Barrios, Rolando; Farley, John D; Montaner, Julio S; Montessori, Valentina C; Walker, David C; Côté, Hélène C F

2008-06-19

Liver mitochondrial toxicity is a concern, particularly in HIV/hepatitis C virus (HCV) coinfection. Liver biopsies from HIV/HCV co-infected patients, 14 ON-highly active antiretroviral therapy (HAART) and nine OFF-HAART, were assessed by electron microscopy quantitative morphometric analyses. Hepatocytes tended to be larger ON-HAART than OFF-HAART (P = 0.05), but mitochondrial volume, cristae density, lipid volume, mitochondrial DNA and RNA levels were similar. We found no evidence of increased mitochondrial toxicity in individuals currently on HAART, suggesting that concomitant HAART should not delay HCV therapy.

Who is accessing public-sector anti-retroviral treatment in the Free State, South Africa? An exploratory study of the first three years of programme implementation

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Booysen Frederik

2010-07-01

Full Text Available Abstract Background Although South Africa has the largest public-sector anti-retroviral treatment (ART programme in the world, anti-retroviral coverage in adults was only 40.2% in 2008. However, longitudinal studies of who is accessing the South African public-sector ART programme are scarce. This study therefore had one main research question: who is accessing public-sector ART in the Free State Province, South Africa? The study aimed to extend the current literature by investigating, in a quantitative manner and using a longitudinal study design, the participants enrolled in the public-sector ART programme in the period 2004-2006 in the Free State Province of South Africa. Methods Differences in the demographic (age, sex, population group and marital status socio-economic (education, income, neo-material indicators, geographic (travel costs, relocation for ART, and medical characteristics (CD4, viral load, time since first diagnosis, treatment status among 912 patients enrolled in the Free State public-sector ART programme between 2004 and 2006 were assessed with one-way analysis of variance, Bonferroni post-hoc analysis, and cross tabulations with the chi square test. Results The patients accessing treatment tended to be female (71.1% and unemployed (83.4%. However, although relatively poor, those most likely to access ART services were not the most impoverished patients. The proportion of female patients increased (P P P P P Conclusions Our analysis showed significant changes in the demographic, socio-economic, geographic, and medical characteristics of the patients during the first three years of the programme. Knowledge of the characteristics of these patients can assist policy makers in developing measures to retain them in care. The information reported here can also be usefully applied to target patient groups that are currently not reached in the implementation of the ART programme.

Amplification and chromosomal dispersion of human endogenous retroviral sequences

International Nuclear Information System (INIS)

Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O'Brien, S.J.

1986-01-01

Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked

Use of Third Line Antiretroviral Therapy in Latin America

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Cesar, Carina; Shepherd, Bryan E.; Jenkins, Cathy A.; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P.; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro

2014-01-01

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. PMID:25221931

Use of third line antiretroviral therapy in Latin America.

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Carina Cesar

Full Text Available 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.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.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.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.

Retinite por citomegalovírus em pacientes pediátricos infectados pelo vírus da imunodeficiência humana em tratamento com "highly active antiretrovirus therapy" Cytomegalovirus retinitis in pediatric patients with AIDS receiving highly active antiretrovirus therapy

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Maria Angélica Dimantas

2004-09-01

inhibitors (HAART. METHODS: Three cases of HIV-infected children taking highly active antiretrovirus therapy (HAART underwent an ocular examination at a university referral center - UNIFESP. RESULTS: The average age was 6 years (10 months to 13 years old, and all of them were C3 (CDC - Atlanta - EUA 1994. Median CD4 cell count and plasma HIV RNA were 67 cells/mm³ (43 - 98 cells/ mm³ and 190.000 copies/ml (53.600 - 460.000 copies/ml. The three patients presented HAART failure and all of them were treated with anti-CMV agents without success. CONCLUSION: The unprecedented benefits resulting from highly active antiretroviral therapy (HAART have been well described. However, treatment failure has become increasingly complex, because of the aggressive forms of opportunistic diseases like CMV retinitis, despite anti-CMV agents. Prompt diagnosis and treatment are essential to minimize the risk of long-term loss of vision for these infected children.

Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans.

Science.gov (United States)

Candotti, Fabio; Shaw, Kit L; Muul, Linda; Carbonaro, Denise; Sokolic, Robert; Choi, Christopher; Schurman, Shepherd H; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G Jayashree; Fu, Pei-Yu; Gschweng, Eric; Cooper, Aaron; Tisdale, John F; Weinberg, Kenneth I; Crooks, Gay M; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Wayne, Alan S; Rosenblatt, Howard M; Davis, Carla M; Hanson, Celine; Rishi, Radha G; Wang, Xiaoyan; Gjertson, David; Yang, Otto O; Balamurugan, Arumugam; Bauer, Gerhard; Ireland, Joanna A; Engel, Barbara C; Podsakoff, Gregory M; Hershfield, Michael S; Blaese, R Michael; Parkman, Robertson; Kohn, Donald B

2012-11-01

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency.

Gene therapy for adenosine deaminase–deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans

Science.gov (United States)

Candotti, Fabio; Shaw, Kit L.; Muul, Linda; Carbonaro, Denise; Sokolic, Robert; Choi, Christopher; Schurman, Shepherd H.; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G. Jayashree; Fu, Pei-Yu; Gschweng, Eric; Cooper, Aaron; Tisdale, John F.; Weinberg, Kenneth I.; Crooks, Gay M.; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Wayne, Alan S.; Rosenblatt, Howard M.; Davis, Carla M.; Hanson, Celine; Rishi, Radha G.; Wang, Xiaoyan; Gjertson, David; Yang, Otto O.; Balamurugan, Arumugam; Bauer, Gerhard; Ireland, Joanna A.; Engel, Barbara C.; Podsakoff, Gregory M.; Hershfield, Michael S.; Blaese, R. Michael; Parkman, Robertson

2012-01-01

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)–deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34+ cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m2). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency. PMID:22968453

Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors

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Victor M. Bii

2016-10-01

Full Text Available Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations. They can also be used for almost any human cancer due to the broad tropism of the vectors. Replication-incompetent retroviral vectors have the ability to dysregulate nearby cancer genes via several mechanisms including enhancer-mediated activation of gene promoters. The integrated provirus acts as a unique molecular tag for nearby candidate driver genes which can be rapidly identified using well established methods that utilize next generation sequencing and bioinformatics programs. Recently, retroviral vector screens have been used to efficiently identify candidate driver genes in prostate, breast, liver and pancreatic cancers. Validated driver genes can be potential therapeutic targets and biomarkers. In this review, we describe the emergence of retroviral insertional mutagenesis screens using replication-incompetent retroviral vectors as a novel tool to identify cancer driver genes in different cancer types.

Correlates of highly active antiretroviral therapy adherence among ...

African Journals Online (AJOL)

Correlates of highly active antiretroviral therapy adherence among urban Ethiopian clients. ... clients' self-reported adherence to HAART medication, a descriptive, comparative cross-sectional study was carried out among adults receiving HAART medication at the Zewditu Memorial Hospital ART clinic in Addis Ababa.

Circulating Cxcr5-Expressing Cd8+T-Cells are Major Producers of Il-21 and Associate with Limited Hiv Replication.

Science.gov (United States)

Perdomo-Celis, Federico; Taborda, Natalia A; Rugeles, Maria T

2018-04-10

Despite advances made with the highly active anti-retroviral therapy (HAART) in the control of the human immunodeficiency virus 1 (HIV) infection, a cure has not been achieved due to the persistence of viral reservoirs. The major HIV reservoirs remain in the lymphoid follicles due to, among other factors, the partial absence of CD8T-cells in these structures. Recently, lymphoid follicle-confined and circulating CD8T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, possessing antiviral mechanisms which could help to control HIV replication. and methods: By flow cytometry, we characterized the phenotype and function of circulating CXCR5-expressing CD8T-cells in HIV-infected patients with natural or HAART-induced control of HIV replication. Circulating CXCR5-expressing CD8T-cells exhibited low or null expression of the C-C chemokine receptor type 7 (CCR7) and had a transitional memory phenotype. Particular redistributions of CXCR5-expressing CD8T-cells were found in HIV-infected patients, and they were partially restored by HAART. The frequency of CXCR5CCR7CD8T-cells was higher in spontaneous HIV controllers and negatively correlated with plasma HIV RNA levels. Total and HIV-specific CXCR5CD8T-cells were major producers of interleukin-21, and this function was positively associated with their interferon-γ production. Circulating CXCR5-expressing CD8T-cells are associated with low level HIV replication, could be novel correlates of protection and potentially useful in the eradication of HIV reservoirs.

Survival and predictors of mortality among human immunodeficiency virus patients on anti-retroviral treatment at Jinka Hospital, South Omo, Ethiopia: a six years retrospective cohort study

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Ameni, Gobena

2016-01-01

OBJECTIVES The survival rate of human immunodeficiency virus (HIV)-infected patients receiving treatment in Ethiopia is poorly understood. This study aimed to determine the survival rate and predictors of mortality among HIV-infected adults on antiretroviral therapy (ART) at Jinka Hospital, South Omo, Ethiopia. METHODS A 6-year retrospective cohort study was conducted using 350 patient records drawn from 1,899 patients on ART at Jinka Hospital from September 2010 to August 2015. The data were analyzed using Kaplan-Meier statistics and Cox regression models. RESULTS Of the 350 study participants, 315 (90.0%) were censored and 35 (10.0%) died. Twenty-two (62.9%) of the deaths occurred during the first year of treatment. The total follow-up encompassed 1,995 person-years, with an incidence rate of 1.75 deaths per 100 person-years. The mean survival time of patients on highly active antiretroviral therapy (HAART) was 30.84±19.57 months. The overall survival of patients on HAART was 64.00% (95% confidence interval [CI], 61.85 to 66.21%) at 72 months of follow-up. The significant predictors of mortality included non-disclosure of HIV status (adjusted hazard ratio [aHR], 5.82; 95% CI, 1.91 to 17.72), a history of tuberculosis (aHR, 1.82; 95% CI, 1.41 to 3.51), and ambulatory (aHR, 2.97; 95% CI, 1.20 to 8.86) or bedridden (aHR, 4.67; 95% CI, 1.30 to 17.27) functional status, World Health Organization (WHO) clinical stage IV illness (aHR, 24.97; 95% CI, 2.75 to 26.45), and substance abusers (aHR, 3.72; 95% CI, 1.39 to 9.97). CONCLUSIONS Patients with a history of tuberculosis treatment, ambulatory or bedridden functional status, or advanced WHO clinical stage disease, as well substance abusers, should be carefully monitored, particularly in the first few months after initiating antiretroviral therapy. Patients should also be encouraged to disclose their status to their relatives. PMID:27820957

Survival and predictors of mortality among human immunodeficiency virus patients on anti-retroviral treatment at Jinka Hospital, South Omo, Ethiopia: a six years retrospective cohort study

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Erdaw Tachbele

2016-11-01

Full Text Available OBJECTIVES The survival rate of human immunodeficiency virus (HIV-infected patients receiving treatment in Ethiopia is poorly understood. This study aimed to determine the survival rate and predictors of mortality among HIV-infected adults on antiretroviral therapy (ART at Jinka Hospital, South Omo, Ethiopia. METHODS A 6-year retrospective cohort study was conducted using 350 patient records drawn from 1,899 patients on ART at Jinka Hospital from September 2010 to August 2015. The data were analyzed using Kaplan-Meier statistics and Cox regression models. RESULTS Of the 350 study participants, 315 (90.0% were censored and 35 (10.0% died. Twenty-two (62.9% of the deaths occurred during the first year of treatment. The total follow-up encompassed 1,995 person-years, with an incidence rate of 1.75 deaths per 100 person-years. The mean survival time of patients on highly active antiretroviral therapy (HAART was 30.84±19.57 months. The overall survival of patients on HAART was 64.00% (95% confidence interval [CI], 61.85 to 66.21% at 72 months of follow-up. The significant predictors of mortality included non-disclosure of HIV status (adjusted hazard ratio [aHR], 5.82; 95% CI, 1.91 to 17.72, a history of tuberculosis (aHR, 1.82; 95% CI, 1.41 to 3.51, and ambulatory (aHR, 2.97; 95% CI, 1.20 to 8.86 or bedridden (aHR, 4.67; 95% CI, 1.30 to 17.27 functional status, World Health Organization (WHO clinical stage IV illness (aHR, 24.97; 95% CI, 2.75 to 26.45, and substance abusers (aHR, 3.72; 95% CI, 1.39 to 9.97. CONCLUSIONS Patients with a history of tuberculosis treatment, ambulatory or bedridden functional status, or advanced WHO clinical stage disease, as well substance abusers, should be carefully monitored, particularly in the first few months after initiating antiretroviral therapy. Patients should also be encouraged to disclose their status to their relatives.

Risk Behaviors of Youth Living With HIV: Pre- and Post-HAART

Science.gov (United States)

Lightfoot, Marguerita; Swendeman, Dallas; Rotheram-Borus, Mary Jane; Comulada, W. Scott; Weiss, Robert

2005-01-01

Objective: To examine the transmission behavior among youth living with HIV (YLH), pre- and post-HAART. Methods: Two cohorts were recruited: (1) 349 YLH during 1994 to 1996 and (2) 175 YLH during 1999 to 2000, after the wide availability of HAART. Differences in sexual and substance-use risk acts and quality of life were examined. Results:…

Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy

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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.

Ocularhaemodynamics parameters of asymptomatic HAART ...

African Journals Online (AJOL)

Results: Vmax of blood flow in central retinal artery (CRA) of asymptomatic HAART - experienced HIV infected children was 12.2cm/s while that of seronegative children was 13.4 cm/s. The PI and RI of blood flow in CRA of asymptomatic HAARTexperienced HIV-infected children were 0.8 and 0.5 respectively while those of ...

Multi point of care instrument evaluation for use in anti-retroviral clinics in South Africa.

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Gounden, Verena; George, Jaya

2012-01-01

South Africa has the largest prevalence of HIV infected individuals in the world. The introduction of point of care testing to anti-retroviral (ARV) clinic sites is hoped to fast track initiation of patients on ARVs and to allow for earlier recognition of adverse effects such as dyslipidaemia, renal and hepatic dysfunction. We evaluated six instruments for the following analytes: glucose, lactate, creatinine, cholesterol, triglycerides, HDL-cholesterol, alanine transaminase (ALT), and glycated haemoglobin. Comparisons with the central laboratory analyser were performed as well as precision studies. A scoring system was developed by the authors to evaluate the instruments in terms of analytical performance, cost, ease of use, and other operational characteristics. As one of the goals of the placement of these instruments was that their operation was simple enough to be used by non-laboratory staff, ease of use contributed a large proportion to the final scoring. Analytical performance of the POC analysers were generally similar, however, there were significant differences in operational characteristics and ease of use. Bias for the different analytes when compared to the laboratory analyser ranged from -27% to 14%. Calculated total errors for all analytes except for HDL cholesterol were within total allowable error recommendations. The two instruments (Roche Reflotron and Cholestech LDX) with the highest overall total points achieved the highest scores for ease of use. This pilot study has led to the development of a scoring system for the evaluation of POC instruments.

Novel agents for anti-platelet therapy

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Ji Xuebin

2011-11-01

Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

Newer trends in the management of genital herpes

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Nath Amiya

2009-01-01

Full Text Available Management of genital herpes is complex. Apart from using the standard antivirals, an ideal management protocol also needs to address various aspects of the disease, including the psychological morbidity. Oral acyclovir, valacyclovir or famciclovir are recommended for routine use. Long-term suppressive therapy is effective in reducing the number of recurrences and the risk of transmission to others. Severe or disseminated disease may require intravenous therapy. Resistant cases are managed with foscarnet or cidofovir. Genital herpes in human immunodeficiency virus-infected individuals usually needs a longer duration of antiviral therapy along with continuation of highly active anti retroviral therapy (HAART. Genital herpes in late pregnancy increases the risk of neonatal herpes. Antiviral therapy and/or cesarean delivery are indicated depending on the clinical circumstance. Acyclovir appears to be safe in pregnancy. But, there is limited data regarding the use of valacyclovir and famciclovir in pregnancy. Neonatal herpes requires a higher dose of acyclovir given intravenously for a longer duration. Management of the sex partner, counseling and prevention advice are equally important in appropriate management of genital herpes. Vaccines till date have been marginally effective. Helicase-primase inhibitors, needle-free mucosal vaccine and a new microbicide product named VivaGel may become promising treatment options in the future.

The effect of incident tuberculosis on immunological response of HIV patients on highly active anti-retroviral therapy at the university of Gondar hospital, northwest Ethiopia: a retrospective follow-up study.

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Assefa, Abate; Gelaw, Baye; Getnet, Gebeyaw; Yitayew, Gashaw

2014-08-27

Human immunodeficiency virus (HIV) infection is usually complicated by high rates of tuberculosis (TB) co-infection. Impaired immune response has been reported during HIV/TB co-infection and may have significant effect on anti-retroviral therapy (ART). TB/HIV co - infection is a major public health problem in Ethiopia. Therefore, the aim of the study was to assess the effect of TB incidence on immunological response of HIV patients during ART. A retrospective follow-up study was conducted among adult HIV patients who started ART at the University of Gondar Hospital. Changes in CD4+ T - lymphocyte count and incident TB episodes occurring during 42 months of follow up on ART were assessed. Life table was used to estimate the cumulative immunologic failure. Kaplan-Meier curve was used to compare survival curves between the different categories. Cox-proportional hazard model was employed to examine predictors of immunological failure. Among 400 HIV patients, 89(22.2%) were found to have immunological failure with a rate of 8.5 per 100 person-years (PY) of follow-up. Incident TB developed in 26(6.5%) of patients, with an incidence rate of 2.2 cases per 100 PY. The immunological failure rate was high (20.1/100PY) at the first year of treatment. At multivariate analysis, Cox regression analysis showed that baseline CD4+ T - cell count immunological failure. There was borderline significant association with incident TB (AHR 2.2; 95%CI: 0.94 - 5.09, p = 0.06). The risk of immunological failure was significantly higher (38.5%) among those with incident TB compared with TB - free (21.1%) (Log rank p = 0.036). High incidence of immunological failure occurred within the first year of initiating ART. The proportions of patients with impaired immune restoration were higher among patients with incident TB. Lower baseline CD4+ T - cells count of immunological failure. The result highlighted the beneficial effects of earlier initiation of ART on CD4+ T - cell count recovery.

Astrocyte Senescence and Metabolic Changes in Response to HIV Antiretroviral Therapy Drugs

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Justin Cohen

2017-08-01

Full Text Available With the advent of highly active antiretroviral therapy (HAART survival rates among patients infected by HIV have increased. However, even though survival has increased HIV-associated neurocognitive disorders (HAND still persist, suggesting that HAART-drugs may play a role in the neurocognitive impairment observed in HIV-infected patients. Given previous data demonstrating that astrocyte senescence plays a role in neurocognitive disorders such as Alzheimer’s disease (AD, we examined the role of HAART on markers of senescence in primary cultures of human astrocytes (HAs. Our results indicate HAART treatment induces cell cycle arrest, senescence-associated beta-galactosidase, and the cell cycle inhibitor p21. Highly active antiretroviral therapy treatment is also associated with the induction of reactive oxygen species and upregulation of mitochondrial oxygen consumption. These changes in mitochondria correlate with increased glycolysis in HAART drug treated astrocytes. Taken together these results indicate that HAART drugs induce the senescence program in HAs, which is associated with oxidative and metabolic changes that could play a role in the development of HAND.

Adrenaline-induced mobilization of T cells in HIV-infected patients

DEFF Research Database (Denmark)

Søndergaard, S R; Cozzi-Lepri, A; Ullum, H

2000-01-01

The present study aimed to investigate lymphocyte mobilization from peripheral cell reservoirs in HIV-infected patients. Nine HIV-infected patients on stable highly active anti-retroviral therapy (HAART), eight treatment-naive HIV-infected patients and eight HIV- controls received a 1-h adrenaline...... infusion. The adrenaline infusion induced a three-fold increase in the concentration of lymphocytes in all three groups. All HIV-infected patients mobilized significantly higher numbers of CD8+ cells but less CD4+ cells. All subjects mobilized CD45RA+CD62L+ and CD8+CD28+ cells to a lesser extent than CD45......RO+CD45RA- and CD8+CD28-cells. Furthermore, high numbers of CD8+CD38+ cells were mobilized only in the HIV-infected patients. It was therefore predominantly T cells with an activated phenotype which were mobilized after adrenaline stimulation. It is concluded that the HIV-associated immune defect...

Effectiveness and Safety of Immunomodulators with Anti-TNF Therapy in Crohn's Disease

Science.gov (United States)

Osterman, Mark T.; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M.; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R.; Lewis, James D.

2015-01-01

Background & Aims The benefit of continuing immunomodulators when “stepping up” to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. Methods We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared using 3 metrics of effectiveness – surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery – and 2 metrics of safety – serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Results Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as “step up” after thiopurine therapy. The rates of surgery (hazard ratio [HR] 1.20, 95% CI 0.73-1.96), hospitalization (HR 0.82 [0.57-1.19]), discontinuation of anti-TNF therapy or surgery (HR 1.09, [0.88-1.34]), and serious infection (HR 0.93 [0.88-1.34]) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risk of opportunistic infection (HR 2.64 [1.21-5.73]) and herpes zoster (HR 3.16 [1.25-7.97]) were increased with combination therapy. Conclusions We found that continuation of immunomodulators after “stepping up” to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. PMID:25724699

Regulatory T cells in human immunodeficiency virus-infected patients are elevated and independent of immunological and virological status, as well as initiation of highly active anti-retroviral therapy

DEFF Research Database (Denmark)

Gaardbo, J.C.; Nielsen, S.D.; Vedel, S.J.

2008-01-01

Infection with human immunodeficiency virus (HIV) causes a dysregulation of the immune system. This is caused by HIV-specific as well as non-specific mechanisms and has not been explained fully. In particular, knowledge is lacking about the potential role of host-mediated immunosuppressive mechan......(regs) was found to be independent of both immunological and virological status, indicating that initiation of HAART has minor effects on the T(reg) level in HIV-infected patients....

Advancements in anti-inflammatory therapy for dry eye syndrome.

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McCabe, Erin; Narayanan, Srihari

2009-10-01

The goal of this literature review is to discuss recent discoveries in the pathophysiology of dry eye and the subsequent evolution of diagnostic and management techniques. The mechanisms of various anti-inflammatory treatments are reviewed, and the efficacy of common pharmacologic agents is assessed. Anti-inflammatory therapy is evaluated in terms of its primary indications, target population, and utility within a clinical setting. The Medline PubMed database and the World Wide Web were searched for current information regarding dry eye prevalence, pathogenesis, diagnosis, and management. After an analysis of the literature, major concepts were integrated to generate an updated portrayal of the status of dry eye syndrome. Inflammation appears to play a key role in perpetuating and sustaining dry eye. Discoveries of inflammatory markers found within the corneal and conjunctival epithelium of dry eye patients have triggered recent advancements in therapy. Pharmacologic anti-inflammatory therapy for dry eye includes 2 major categories: corticosteroids and immunomodulatory agents. Fatty acid and androgen supplementation and oral antibiotics have also shown promise in dry eye therapy because of their anti-inflammatory effects. Anti-inflammatory pharmacologic agents have shown great success in patients with moderate to severe dry eye when compared with alternative treatment modalities. A deeper understanding of the link between inflammation and dry eye validates the utilization of anti-inflammatory therapy in everyday optometric practice.

CHILDREN'S ADHERENCE TO HAART ADHERENCE

African Journals Online (AJOL)

han or equal IQ 2 log" and in 64% of children wirh smaller man 2 log,o decrease in viral load. Secondly, i caregivers are not well prepared for adherence issues before starting HAART, or if regimens are too onerous to follow, treatment is likely to fail. Every effort should be made to see the burden of adherence from the.

[Adverse side effects of antiretroviral therapy: relationship between patients' perception and adherence].

Science.gov (United States)

Martín, María Teresa; del Cacho, Elena; López, Ester; Codina, Carles; Tuset, Montserrat; de Lazzari, Elisa; Miró, Josep M; Gatell, Josep M; Ribas, Josep

2007-06-23

To evaluate the relationship between perceived adverse side effects (AE) and non-adherence associated with highly active antiretroviral therapy (HAART). For 6 consecutive months, patients taking HAART who came to the Pharmacy Department were interviewed. In the questionnaire they had to answer if they had experienced any AE over the past 6 months, what did they do in response to AE and what was the clinical evolution. Adherence was measured by pill counts or by pharmacy records (when pill counts were not possible). Of 1,936 interviewed patients, 661 (34.1%) reported AE over the past 6 months. The type of antiretroviral drug regimen and starting, re-starting or changing HAART over the past 6 months were significantly associated with AE. Patients who reported AE were 1.4 times more likely to be non-adherents. The most frequently reported AE were diarrhea followed by central nervous system abnormalities and by other gastrointestinal disturbances. In patients starting HAART, 62% of AE improved or disappeared during the first 4 weeks of therapy. Patients who report AE have worst adherence. AE are more frequent in patients starting HAART but in most cases they improve with time and/or symptomatic therapy.

[Mechanisms of retroviral immunosuppressive domain-induced immune modulation].

Science.gov (United States)

Blinov, V M; Krasnov, G S; Shargunov, A V; Shurdov, M A; Zverev, V V

2013-01-01

Immunosuppressive domains (ISD) of viral envelope glycoproteins provide highly pathogenic phenotypes of various retroviruses. ISD interaction with immune cells leads to an inhibition of a response. In the 1980s it was shown that the fragment of ISD comprising of 17 amino acids (named CKS-17) is carrying out such immune modulation. However the underlying mechanisms were not known. The years of thorough research allowed to identify the regulation of Ras-Raf-MEK-MAPK and PI3K-AKT-mTOR cellular pathways as a result of ISD interaction with immune cells. By the way, this leads to decrease of secretion of stimulatory cytokines (e.g., IL-12) and increase of inhibitory, anti-inflammatory ones (e.g., IL-10). One of the receptor tyrosine kinases inducing signal in these pathways acts as the primary target of ISD while other key regulators--cAMP and diacylglycerol (DAG), act as secondary messengers of signal transduction. Immunosuppressive-like domains can be found not only in retroviruses; the presence of ISD within Ebola viral envelope glycoproteins caused extremely hard clinical course of virus-induced hemorrhagic fever. A number of retroviral-origin fragments encoding ISD can be found in the human genome. These regions are expressed in the placenta within genes of syncytins providing a tolerance of mother's immune system to an embryo. The present review is devoted to molecular aspects of retroviral ISD-induced modulation of host immune system.

Highly active antiretroviral therapy and employment status in Accra ...

African Journals Online (AJOL)

Demographic charac-teristics were tested as predictors of immunological response while on HAART using hierarchical linear models. Setting: Fevers Unit, Korle-Bu Teaching Hospital, Accra, Ghana Participants: Subjects comprised a convenience sam-ple of adult HAART patients receiving therapy for at least 9 months.

Acceptance-based behavior therapy to promote HIV medication adherence.

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Moitra, Ethan; Herbert, James D; Forman, Evan M

2011-12-01

A significant number of adults with HIV in the USA do not maintain adherence to highly active antiretroviral therapy (HAART) at adequate levels. Although traditional cognitive behavioral interventions have shown promise in promoting HAART adherence, acceptance-based behavior therapy (ABBT) may be particularly useful in this population. ABBT has the potential to overcome common avoidance-based barriers associated with poor adherence, including denial of various illness-related factors and avoidance of stigmatization. We describe the rationale for promoting psychological and behavioral acceptance in HIV-positive populations; outline an ABBT to promote HAART adherence targeting primary care patients from urban, minority, low socioeconomic backgrounds; and report preliminary qualitative observations of treatment feasibility and acceptability.

Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections.

Science.gov (United States)

Roy, Upal; Barber, Paul; Tse-Dinh, Yuk-Ching; Batrakova, Elena V; Mondal, Debasis; Nair, Madhavan

2015-01-01

Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function, and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

Role of MRP Transporters in Regulating Antimicrobial Drug Inefficacy and Oxidative Stress-induced Pathogenesis during HIV-1 and TB Infections

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Upal eRoy

2015-09-01

Full Text Available Multi-Drug Resistance Proteins (MRPs are members of the ATP binding cassette (ABC drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV used in highly active antiretroviral therapy (HAART and antibacterial agents used in Tuberculus Bacilli (TB therapy. Due to their role in efflux of glutathione (GSH conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9 have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

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Wilke Claus O

2008-01-01

Full Text Available Abstract Background In the setting of highly active antiretroviral therapy (HAART, plasma levels of human immunodeficiency type-1 (HIV-1 rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4+ T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. Methods Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. Results By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. Conclusion The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.

Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

Science.gov (United States)

Sedaghat, Ahmad R; Siliciano, Robert F; Wilke, Claus O

2008-01-01

Background In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4+ T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. Methods Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. Results By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. Conclusion The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir. PMID:18171475

The peri-operative management of anti-platelet therapy in elective, non-cardiac surgery.

Science.gov (United States)

Alcock, Richard F; Naoum, Chris; Aliprandi-Costa, Bernadette; Hillis, Graham S; Brieger, David B

2013-07-31

Cardiovascular complications are important causes of morbidity and mortality in patients undergoing elective non-cardiac surgery, with adverse cardiac outcomes estimated to occur in approximately 4% of all patients. Anti-platelet therapy withdrawal may precede up to 10% of acute cardiovascular syndromes, with withdrawal in the peri-operative setting incompletely appraised. The aims of our study were to determine the proportion of patients undergoing elective non-cardiac surgery currently prescribed anti-platelet therapy, and identify current practice in peri-operative management. In addition, the relationship between management of anti-platelet therapy and peri-operative cardiac risk was assessed. We evaluated consecutive patients attending elective non-cardiac surgery at a major tertiary referral centre. Clinical and biochemical data were collected and analysed on patients currently prescribed anti-platelet therapy. Peri-operative management of anti-platelet therapy was compared with estimated peri-operative cardiac risk. Included were 2950 consecutive patients, with 516 (17%) prescribed anti-platelet therapy, primarily for ischaemic heart disease. Two hundred and eighty nine (56%) patients had all anti-platelet therapy ceased in the peri-operative period, including 49% of patients with ischaemic heart disease and 46% of patients with previous coronary stenting. Peri-operative cardiac risk score did not influence anti-platelet therapy management. Approximately 17% of patients undergoing elective non-cardiac surgery are prescribed anti-platelet therapy, the predominant indication being for ischaemic heart disease. Almost half of all patients with previous coronary stenting had no anti-platelet therapy during the peri-operative period. The decision to cease anti-platelet therapy, which occurred commonly, did not appear to be guided by peri-operative cardiac risk stratification. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Novel β-amyloid aggregation inhibitors possessing a turn mimic.

Science.gov (United States)

Hamada, Yoshio; Miyamoto, Naoko; Kiso, Yoshiaki

2015-04-01

Amyloid β peptide, the main component of senile plaques found in the brain of Alzheimer disease (AD) patients, is a molecular target for AD therapeutic intervention. A number of potential AD therapeutics have been reported, including inhibitors of β-secretase, γ-secretase, and Aβ aggregation, and anti-amyloid agents, such as neprilysin, insulin degrading enzyme (IDE), and Aβ antibodies. Recently, we reported potent small-sized β-secretase (BACE1) inhibitors, which could serve as anti-AD drugs. However AD is a progressive disorder, where dementia symptoms gradually worsen over several decades, and therefore may require many years to get cured. One possible way to achieve a greater therapeutic effect is through simultaneous administration of multiple drugs, similar to those used in Highly Active Anti-Retroviral Therapy (HAART) used to treat AIDS. In order to overcome AD, we took a drug discovery approach to evaluate, novel β-amyloid aggregation inhibitors. Previously, we reported that a tong-type compound possessing a turn mimic as the inhibitor of HIV-1 protease dimerization. Oligomerized amyloid β peptides contain a turn structure within the molecule. Here, we designed and synthesized novel β-amyloid aggregation inhibitors with a turn-mimic template, based on the turn conformer of the oligomerized amyloid β peptides. Copyright © 2015 Elsevier Ltd. All rights reserved.

Addressing the fear and consequences of stigmatization - a necessary step towards making HAART accessible to women in Tanzania: a qualitative study

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Gerstoft Jan

2011-08-01

Full Text Available Abstract Background Highly Active Antiretroviral Therapy (HAART has been available free of charge in Tanga, Tanzania since 2005. However we have found that a high percentage of women referred from prevention of mother-to-child transmission services to the Care and Treatment Clinics (CTC for HAART never registered at the CTCs. Few studies have focused on the motivating and deterring factors to presenting for HAART particularly in relation to women. This study seeks to remedy this gap in knowledge. Methodology A qualitative approach using in-depth interviews and focus group discussions was chosen to understand these issues as perceived and interpreted by HIV infected women themselves. Results The main deterrent to presenting for treatment appears to be fear of stigmatization including fear of ostracism from the community, divorce and financial distress. Participants indicated that individual counselling and interaction with other people living with HIV encourages women, who are disinclined to present for HAART, to do so, and that placing the entrance to the CTC so as to provide discrete access increases the accessibility of the clinic. Conclusion Combating stigma in the community, although it is essential, will take time. Therefore necessary steps towards encouraging HIV infected women to seek treatment include reducing self-stigma, assisting them to form empowering relationships and to gain financial independence and emphasis by example of the beneficial effect of treatment for themselves and for their children. Furthermore ensuring a discrete location of the CTC can increase its perceived accessibility.

Prevalence of hearing-loss among HAART-treated children in the Horn of Africa.

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Smith, Alden F; Ianacone, David C; Ensink, Robbert J H; Melaku, Abebe; Casselbrant, Margaretha L; Isaacson, Glenn

2017-07-01

The prevalence of hearing loss (HL) in children infected with HIV/AIDS is not well studied. Even fewer studies focus on stable HIV-infected children treated with high-effective antiretroviral therapy (HAART). We aim to compare the prevalence of ear disease and HL in HAART-treated, HIV + children in Addis Ababa, Ethiopia with a well, similarly-aged elementary school population with unknown HIV status (HIVU). Children underwent standard head and neck examination and cerumen removal by board certified otolaryngologists. Next, certified audiologists performed hearing screening with pure-tone audiometry using a circumaural headset but without an ambient noise reducing environment. Children failing audiometric screening underwent full behavioral audiometry including air and bone testing. The primary outcome parameter was HL > 25 dB with the audiologist accounting for background noise. A second endpoint was PTA >40 dB (500, 1000, 2000 Hz) without assessment of background noise. 107 HIV+ and 147 HIVU children met inclusion criteria. In the HIV + cohort 17.8% had evidence of TM perforations and 8.4% had otorrhea. In the HIVU group 2.7% had a TM perforation and 0% had otorrhea. Hearing was significantly worse in HIV + children. (Audiologist determination: 38.3% HL HIV+, 12.2% HIVU, Fisher's-Exact-Test OR: 4.5, 95% CI 2.4-8.3, p-value hearing-ear PTA > 40 dB: 19.6% HL HIV+, 6.1% HIVU, OR: 3.7, 95% CI 1.7-8.4, p-value hearing losses are significantly more common in HAART-treated HIV + children than in well, similarly-aged controls. Rates of SNHL are similar. Copyright © 2017 Elsevier B.V. All rights reserved.

Acceptance of anti-retroviral therapy among patients infected with HIV and tuberculosis in rural Malawi is low and associated with cost of transport.

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Rony Zachariah

Full Text Available BACKGROUND: A study was conducted among newly registered HIV-positive tuberculosis (TB patients systematically offered anti-retroviral treatment (ART in a district hospital in rural Malawi in order to a determine the acceptance of ART b conduct a geographic mapping of those placed on ART and c examine the association between "cost of transport" and ART acceptance. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cross-sectional analysis was performed on routine program data for the period of February 2003 to July 2004. Standardized registers and patient cards were used to gather data. The place of residence was used to determine road distances to the Thyolo district hospital. Cost of transport from different parts of the district was based on the known cost for public transport to the road-stop closest to the patient's residence. Of 1,290 newly registered TB patients, 1,003(78% underwent HIV-testing of whom 770 (77% were HIV-positive. 742 of these individuals (pulmonary TB = 607; extra-pulmonary TB = 135 were considered eligible for ART of whom only 101(13.6% accepted ART. Cost of transport to the hospital ART site was significantly associated with ART acceptance and there was a linear trend in association between cost and ART acceptance (chi(2 for trend = 25.4, P<0.001. Individuals who had to pay 50 Malawi Kwacha (1 United States Dollar = 100 Malawi Kwacha, MW or less for a one-way trip to the Thyolo hospital were four times more likely to accept ART than those who had to pay over 100 MW (Adjusted Odds ratio = 4.0, 95% confidence interval: 2.0-8.1, P<0.001. CONCLUSIONS/SIGNIFICANCE: ART acceptance among TB patients in a rural district in Malawi is low and associated with cost of transport to the centralized hospital based ART site. Decentralizing the ART offer from the hospital to health centers that are closer to home communities would be an essential step towards reducing the overall cost and burden of travel.

Dyslipidemia in HIV Infected Children Receiving Highly Active Antiretroviral Therapy.

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Mandal, Anirban; Mukherjee, Aparna; Lakshmy, R; Kabra, Sushil K; Lodha, Rakesh

2016-03-01

To assess the prevalence of dyslipidemia and lipodystrophy in Indian children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI) based highly active antiretroviral therapy (HAART) and to determine the associated risk factors for the same. The present cross-sectional study was conducted at a Pediatric Clinic of a tertiary care teaching center in India, from May 2011 through December 2012. HIV infected children aged 5-15 y were enrolled if they did not have any severe disease or hospital admission within last 3 mo or receive any medications known to affect the lipid profile. Eighty-one children were on highly active antiretroviral therapy (HAART) for at least 6 mo and 16 were receiving no antiretroviral therapy (ART). Participants' sociodemographic, nutritional, clinical, and laboratory data were recorded in addition to anthropometry and evidence of lipodystrophy. Fasting lipid profile, apolipoprotein A1 and B levels were done for all the children. Among the children on highly active antiretroviral therapy (HAART), 38.3 % had dyslipidemia and 80.2 % had lipodystrophy, while 25 % antiretroviral therapy (ART) naïve HIV infected children had dyslipidemia. No clinically significant risk factors could be identified that increased the risk of dyslipidemia or lipodystrophy in children on highly active antiretroviral therapy (HAART). There is a high prevalence of dyslipidemia and lipodystrophy in Indian children with HIV infection with an imminent need to establish facilities for testing and treatment of these children for metabolic abnormalities.

Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

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Orekhov, Alexander N

2013-01-01

The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression.

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Trinh, Alice T; Ball, Bret G; Weber, Erin; Gallaher, Timothy K; Gluzman-Poltorak, Zoya; Anderson, French; Basile, Lena A

2009-12-30

Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone. A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection. Vectors that contained the ADA LCR were preferentially expressed in T-cell lines. Further improvements

Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression

Science.gov (United States)

2009-01-01

Background Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone. Methods A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection. Results Vectors that contained the ADA LCR were preferentially expressed in T

Prevalência de sobrepeso e obesidade abdominal em indivíduos portadores de HIV/AIDS, em uso de terapia anti-retroviral de alta potência Prevalence of overweight and central obesity in HIV/AIDS patients treated with highly active antiretroviral therapy

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Patrícia Constante Jaime

2004-03-01

Full Text Available OBJETIVO: Avaliar o estado nutricional de indivíduos portadores do HIV/AIDS em uso de terapia anti-retroviral de alta potência, segundo sexo e número de linfócitos T CD4.+. MATERIAL E MÉTODOS: Estudo transversal envolvendo 223 indivíduos (171 homens e 52 mulheres tratados com inibidores de protease, com idade entre 20 e 59 anos, recrutados em um serviço de referência em tratamento de HIV/AIDS do município de São Paulo. Os dados antropométricos utilizados foram peso, estatura e circunferência da cintura (CC. O índice de massa corporal (IMC foi calculado como a razão entre peso (kg e estatura ao quadrado (m², de acordo com o critério de classificação proposto pela Organização Mundial de Saúde. Os pacientes foram divididos em três categorias por número de linfócitos T CD4.+: 350 (cel/mm³. RESULTADOS: A prevalência de sobrepeso na população foi de 30,5%, e de obesidade abdominal de 12,6%. As mulheres apresentaram prevalência maior de sobrepeso (36,5% e de obesidade abdominal (32,7% quando comparadas aos homens (28,7% e 6,4% respectivamente. A prevalência de baixo peso foi maior nas mulheres (7,7% do que nos homens (2,3%. Ausência de associação significativa entre sobrepeso, obesidade abdominal e número de linfócitos T CD4.+ foi observada tanto nos homens como nas mulheres. CONCLUSÃO: As mulheres apresentaram prevalências maiores de baixo peso, sobrepeso e obesidade abdominal em relação aos homens. A obesidade é o desvio do estado nutricional mais importante, superando a desnutrição, nesta população de indivíduos portadores do HIV/AIDS em uso de terapia anti-retroviral de alta potência.OBJECTIVE: To evaluate the nutritional status of HIV/AIDS patients treated with highly active antiretroviral therapy, according to gender and T CD4 + lymphocyte count. MATERIAL AND METHODS: This was a cross-sectional study, including 223 individuals (171 men and 52 women treated with protease inhibitors, aged between 20 and

Anterior segment and external ocular disorders associated with HIV infections in the era of HAART in Chiang Mai University Hospital, a prospective descriptive cross sectional study.

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Singalavanija, Tassapol; Ausayakhun, Somsanguan; Tangmonkongvoragul, Chulaluck

2018-01-01

Human immunodeficiency virus (HIV) causes impairment to the human immune system which leads to immunocompromised conditions, including ocular complications. Several important HIV-associated disorders may involve the anterior segment, ocular surface, and adnexae organ such as dry eye, blepharitis which reduce quality of life of patients. In present, potent antiretroviral therapies HAART (highly active antiretroviral therapy) has improved the length and quality of life which may lead to an increased prevalence of anterior segment ocular disorders. Hence, this study has been undertaken to identify the prevalence and associated factors of anterior segment and external ocular disorder in HIV infected patients in the era of HAART. A prospective descriptive cross sectional study was carried out in HIV positive patients conducted at the Department of Ophthalmology, Chiang Mai University Hospital, from February 2014 to October 2015. Detail history and ocular examination was carried out to examine for anterior segment and external ocular disorders. A total number of 363 patients were included for this prospective cross-sectional study. From the total of 363 patients, 123 patients had an anterior segment and external ocular disorder which account as the prevalence of 33.9%. The most common anterior segment manifestations was dry eye seen in 36 patients (9.9%), followed by posterior blepharitis (Meibomian gland dysfunction) seen in 23 patients (6.3%) and anterior blepharitis seen in 12 patients (3.3%). Other ocular complications included microvasculopathy, immune recovery uveitis, conjunctivitis, papilloma, anterior uveitis, corneal ulcer, nevus, trichiasis, molluscum contangiosum, Kaposi sarcoma, interstitial keratitis, conjunctival lymphangiectasia, dacryocystitis, vernal keratoconjunctivitis and eyelid penicilosis. In this study, the prevalance of anterior segment disorders was higher than in the preHAART era. Dry eye, blepharitis and uveitis were the top three most common

Causes of death among people living with AIDS in the pre- and post-HAART Eras in the city of São Paulo, Brazil.

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Carmen-Silvia Bruniera Domingues

Full Text Available OBJECTIVE: We examine the trend in causes of death among people living with AIDS in the city of São Paulo, Brazil, in the periods before and after the introduction of highly active antiretroviral therapy (HAART, and we investigate potential disparities across districts of residence. METHODS: Descriptive study of three periods: pre-HAART (1991-1996; early post-HAART (1997-1999; and late post-HAART (2000-2006. The data source was the São Paulo State STD/AIDS Program and São Paulo State Data Analysis Foundation. Causes of death were classified by the ICD-9 (1991-1995 and ICD-10 (1996-2006. We estimated age-adjusted mortality rates for leading underlying causes of death and described underlying and associated causes of death according to sociodemographic characteristics and area of residence. We used Pearson's chi-square test or Fisher's exact test to compare categorical variables. Areas of residence were categorized using a socioeconomic index. To analyze trends we apply generalized linear model with Poisson regression. RESULTS: We evaluated 32,808 AIDS-related deaths. Between the pre- and late post-HAART periods, the proportion of deaths whose underlying causes were non-AIDS-related diseases increased from 0.2% to 9.6% (p<0.001: from 0.01% to 1.67% (p<0.001 for cardiovascular diseases; 0.01% to 1.62% (p<0.001 for bacterial/unspecified pneumonia; and 0.03% to 1.46% (p<0.001 for non-AIDS-defining cancers. In the late post-HAART period, the most common associated causes of death were bacterial/unspecified pneumonia (35.94%, septicemia (33.46%, cardiovascular diseases (10.11% and liver diseases (8.0%; and common underlying causes, besides AIDS disease, included non-AIDS-defining cancers in high-income areas, cardiovascular diseases in middle-income areas and assault in low-income areas. CONCLUSIONS: The introduction of HAART has shifted the mortality profile away from AIDS-related conditions, suggesting changes in the pattern of morbidity, but

Immunological Analysis of Treatment Interruption After Early Highly Active Antiretroviral Therapy

NARCIS (Netherlands)

Schellens, Ingrid M. M.; Pogany, Katalin; Westerlaken, Geertje H. A.; Borghans, José A. M.; Miedema, Frank; van Valkengoed, Irene G. M.; Kroon, Frank P.; Lange, Joep M. A.; Brinkman, Kees; Prins, Jan M.; van Baarle, Debbie

2010-01-01

We longitudinally evaluated HIV-specific T-cell immunity after discontinuation of highly active antiretroviral therapy (HAART). After treatment interruption (TI), some individuals could maintain a low plasma viral load ( <15,000 copies/mL), whereas others could not (>50,000 copies/mL). Before HAART

Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era

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Koollawat Chupradit

2017-09-01

Full Text Available Human immunodeficiency virus (HIV is a causative agent of acquired immune deficiency syndrome (AIDS. Highly active antiretroviral therapy (HAART can slow down the replication of HIV-1, leading to an improvement in the survival of HIV-1-infected patients. However, drug toxicities and poor drug administration has led to the emergence of a drug-resistant strain. HIV-1 immunotherapy has been continuously developed, but antibody therapy and HIV vaccines take time to improve its efficiency and have limitations. HIV-1-specific chimeric antigen receptor (CAR-based immunotherapy founded on neutralizing antibodies is now being developed. In HIV-1 therapy, anti-HIV chimeric antigen receptors showed promising data in the suppression of HIV-1 replication; however, autologous transfusion is still a problem. This has led to the development of effective peptides and proteins for an alternative HIV-1 treatment. In this paper, we provide a comprehensive review of potent anti-HIV-1 peptides and proteins that reveal promising therapeutic activities. The inhibitory mechanisms of each therapeutic molecule in the different stages of the HIV-1 life cycle will be discussed herein.

A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.

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Armenia, Daniele; Soulie, Cathia; Di Carlo, Domenico; Fabeni, Lavinia; Gori, Caterina; Forbici, Federica; Svicher, Valentina; Bertoli, Ada; Sarmati, Loredana; Giuliani, Massimo; Latini, Alessandra; Boumis, Evangelo; Zaccarelli, Mauro; Bellagamba, Rita; Andreoni, Massimo; Marcelin, Anne-Geneviève; Calvez, Vincent; Antinori, Andrea; Ceccherini-Silberstein, Francesca; Perno, Carlo-Federico; Santoro, Maria Mercedes

2014-01-01

We previously found that a very low geno2pheno false positive rate (FPR ≤ 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤ 2; 2-5; 5-10; 10-20; 20-60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥ 150 cells/mm(3)) and on the time to achieve virological success (the first HIV-RNA measurement immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤ 2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2-5; 77.5%, FPR 5-10; 71.7%, FPR 10-20; 81.8%, FPR 20-60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤ 2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20-0.71], p = 0.003) and to achieve virological success (0.50 [0.26-0.94], p = 0.031) than those with pre-HAART FPR >60%. Beyond the genotypically-inferred tropism determination, FPR ≤ 2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.

Open ends: an ethnographic radio montage about post-diagnosis lives in Denmark and South Africa

DEFF Research Database (Denmark)

Houmøller, Kathrin; Steno, Anne Mia

This presentation takes the form of a radio montage and presents stories of post-diagnosis lives in Denmark and urban South Africa. Based on ethnographic fieldworks with young people in psychiatric treatment (Denmark) and among hiv-positive people in anti-retroviral therapy (South Africa), the mo......This presentation takes the form of a radio montage and presents stories of post-diagnosis lives in Denmark and urban South Africa. Based on ethnographic fieldworks with young people in psychiatric treatment (Denmark) and among hiv-positive people in anti-retroviral therapy (South Africa...

Effectiveness and Safety of Immunomodulators With Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

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Osterman, Mark T; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R; Lewis, James D

2015-07-01

The benefit of continuing immunomodulators when "stepping up" to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness-surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery-and 2 metrics of safety-serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as "step up" after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73-1.96), hospitalization (HR, 0.82; 0.57-1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88-1.34), and serious infection (HR, 0.93; 0.88-1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21-5.73) and herpes zoster (HR, 3.16; 1.25-7.97) were increased with combination therapy. We found that continuation of immunomodulators after "stepping up" to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Relationship of long-term highly active antiretroviral therapy on salivary flow rate and CD4 Count among HIV-infected patients.

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Kumar, J Vijay; Baghirath, P Venkat; Naishadham, P Parameswar; Suneetha, Sujai; Suneetha, Lavanya; Sreedevi, P

2015-01-01

To determine if long-term highly active antiretroviral therapy (HAART) therapy alters salivary flow rate and also to compare its relation of CD4 count with unstimulated and stimulated whole saliva. A cross-sectional study was performed on 150 individuals divided into three groups. Group I (50 human immunodeficiency virus (HIV) seropositive patients, but not on HAART therapy), Group II (50 HIV-infected subjects and on HAART for less than 3 years called short-term HAART), Group III (50 HIV-infected subjects and on HAART for more than or equal to 3 years called long-term HAART). Spitting method proposed by Navazesh and Kumar was used for the measurement of unstimulated and stimulated salivary flow rate. Chi-square test and analysis of variance (ANOVA) were used for statistical analysis. The mean CD4 count was 424.78 ± 187.03, 497.82 ± 206.11 and 537.6 ± 264.00 in the respective groups. Majority of the patients in all the groups had a CD4 count between 401 and 600. Both unstimulated and stimulated whole salivary (UWS and SWS) flow rates in Group I was found to be significantly higher than in Group II (P flow rate between Group II and III subjects were also found to be statistically significant (P relationship in Group II (P flow rates of HIV-infected individuals who are on long-term HAART.

An information-motivation-behavioral skills model of adherence to antiretroviral therapy.

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Fisher, Jeffrey D; Fisher, William A; Amico, K Rivet; Harman, Jennifer J

2006-07-01

HIV-positive persons who do not maintain consistently high levels of adherence to often complex and toxic highly active antiretroviral therapy (HAART) regimens may experience therapeutic failure and deterioration of health status and may develop multidrug-resistant HIV that can be transmitted to uninfected others. The current analysis conceptualizes social and psychological determinants of adherence to HAART among HIV-positive individuals. The authors propose an information-motivation-behavioral skills (IMB) model of HAART adherence that assumes that adherence-related information, motivation, and behavioral skills are fundamental determinants of adherence to HAART. According to the model, adherence-related information and motivation work through adherence-related behavioral skills to affect adherence to HAART. Empirical support for the IMB model of adherence is presented, and its application in adherence-promotion intervention efforts is discussed.

Magnetic concentration of a retroviral vector using magnetite cationic liposomes.

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Ito, Akira; Takahashi, Tetsuya; Kameyama, Yujiro; Kawabe, Yoshinori; Kamihira, Masamichi

2009-03-01

For tissue engineering purposes, retroviral vectors represent an efficient method of delivering exogenous genes such as growth factors to injured tissues because gene-transduced cells can produce stable and constant levels of the gene product. However, retroviral vector technology suffers from low yields. In the present study, we used magnetite nanoparticles and magnetic force to concentrate the retroviral vectors to enhance the transduction efficiency and to enable their magnetic manipulation. Magnetite nanoparticles modified with cationic liposomes were added to a solution containing a retroviral vector pseudotyped with vesicular stomatitis virus glycoprotein. The magnetic particles that captured the viral vectors were collected using a magnetic force and seeded into mouse neuroblastoma Neuro2a cells. The viral titer was up to 55 times greater (up to 3 x 10(8) infectious units/mL). Additionally, the magnetically labeled retroviral vectors can be directed to the desired regions for infection by applying magnetic fields, and micro-patterns of gene-transduced cell regions could be created on a cellular monolayer using micro-patterned magnetic concentrators. These results suggest that this technique provides a promising approach to capturing and concentrating viral vectors, thus achieving high transduction efficiency and the ability to deliver genes to a specific injured site by applying a magnetic field.

Início da terapia anti-retroviral em estágio avançado de imunodeficiência entre indivíduos portadores de HIV/AIDS em Belo Horizonte, Minas Gerais, Brasil Initiation of antiretroviral therapy in HIV-infected patients with severe immunodeficiency in Belo Horizonte, Minas Gerais State, Brazil

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José Roberto Maggi Fernandes

2009-06-01

Full Text Available O objetivo deste trabalho foi verificar a proporção de início tardio da terapia anti-retroviral (TARV e seus fatores associados. Estudo de corte transversal com pacientes de dois serviços públicos de referência (n = 310 em Belo Horizonte, Minas Gerais, Brasil. Atraso no início da TARV foi definido como ter contagem de linfócitos T CD4+ The main objective was to assess the proportion of delayed initiation of antiretroviral therapy (ART and associated factors. This was a cross-sectional study of 310 patients enrolled in two public health centers in Belo Horizonte, Minas Gerais State, Brazil. Delayed ART initiation was defined as starting treatment with a CD4 count lower than 200 cells/mm³ or clinical symptoms of severe immunodepression at the time of first antiretroviral prescription. The majority of participants were males (63.9%, had no health insurance (76.1%, and started ART less than 120 days after the first medical visit (75.2%. The proportion of delayed ART initiation was 68.4%. Unemployment, referral by a health professional for HIV testing, fewer than two medical visits in the six months prior to ART initiation, and time between first medical visit and ART initiation less than 120 days were independently associated with the outcome. Our results suggest that every patient 13 to 64 years of age should be offered HIV testing, which could increase the rate of early HIV diagnosis, and thus patients that tested positive could benefit from timely follow-up and antiretroviral therapy.

Treinamento físico para indivíduos HIV positivo submetidos à HAART: efeitos sobre parâmetros antropométricos e funcionais Physical training for HIV positive individuals submitted to HAART: effects on anthropometric and functional parameters

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Edmar Lacerda Mendes

2013-02-01

Full Text Available INTRODUÇÃO: A terapia antirretroviral fortemente ativa (HAART tem melhorado a prognose em indivíduos infectados pelo HIV. No entanto, a HAART tem sido associada ao desenvolvimento de anormalidades metabólicas e na distribuição de gordura corporal conhecida como síndrome lipodistrófica associada ao HIV (SLHIV. OBJETIVO: Este estudo investigou o impacto de 24 semanas de exercício resistido com componente aeróbico (ERCA sobre parâmetros antropométricos e funcionais de portadores de HIV submetidos à HAART. MÉTODOS: Noventa e nove indivíduos infectados pelo HIV foram randomicamente alocados em quatro grupos: exercício e lipodistrofia (n = 24; EX+LIP; exercício sem lipodistrofia (n = 21; EX+NoLIP; controle e lipodistrofia (n = 27; NoEX+LIP; controle sem lipodistrofia (n = 27; NoEX+NoLIP. Os indivíduos dos grupos exercitados (EX+LIP e EX+NoLIP participaram de 24 semanas de ERCA. Nos momentos pré e pós 24 semanas de intervenção foram realizadas medidas antropométricas, testes de força e aptidão cardiorrespiratória. RESULTADOS: Vinte e quatro semanas de ERCA alteraram os perímetros corporais avaliados (P INTRODUCTION: The use of highly active antiretroviral therapy (HAART has improved the prognosis of HIV-infected individuals. However, HAART has been associated with the development of metabolic and fat distribution abnormalities, known as HIV-associated lipodystrophy syndrome (SLHIV. OBJECTIVE: This study investigated the impact of 24 weeks of resistance exercise with aerobic component (REAC on anthropometric and functional parameters in HIV-infected patients undergoing HAART. METHODS: Ninety- nine HIV-infected patients were randomly allocated into four groups: exercise and lipodystrophy (n = 24; EX + LIP; exercise without lipodystrophy (n = 21; EX + NoLIP; control and lipodystrophy (n = 27; NoEX + LIP; control without lipodystrophy (n = 27; NoEX + NoLIP. Subjects from exercised groups (EX+LIP and EX+NoLIP participated in a 24

Transient elastography discloses identical distribution of liver fibrosis in chronic hepatitis C between HIV-negative and HIV-positive patients on HAART

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Grünhage F

2010-04-01

Full Text Available Abstract Objective Progressive immunodeficiency associated with HIV-infection leads to a progressive course of liver disease in HIV/HCV-co-infected patients. Highly active antiretroviral therapy (HAART efficiently restores and preserves immune functions and has recently been demonstrated to also result in reduced liver-related mortality in HIV/HCV-co-infected patients. Methods To analyse differences in current liver fibrosis as a possible effect of HAART on fibrosis progression we assessed hepatic fibrosis by transient elastography in a cross-sectional comparison between HCV-mono-infected and HIV/HCV-co-infected patients presenting at our outpatient department in 2007. Results Overall, we did not find any difference in the distribution of liver stiffness between mono- (n = 84 and double-infected (n = 57 patients (14.4 kPa (10.8 - 18.2 versus 12.4 kPa (9.1 - 16.1, mean (95%-CI. However, in the 8 HIV+ patients with CD4 counts Conclusions These findings are in line with other data that show an improved prognosis of chronic hepatitis C in HIV+ patients under effective HAART, and may be a hint that fibrosis progression in well-treated HIV+ patients will no longer be different from that in HCV-mono-infected patients.

Highly active antiretroviral therapy normalizes the function of progenitor cells in human immunodeficiency virus-infected patients

DEFF Research Database (Denmark)

Dam Nielsen, S.; Ersbøll, A. K.; Mathiesen, L.

1998-01-01

-infected patients were determined prior to HAART and after 2, 4, 8, and 12 weeks of therapy. The mean number of colony-forming units (cells) per milliliter (cfu/mL) was 15.0 prior to HAART vs. 109.8 in healthy controls (P.../mL eliminated the differences between HIV-infected patients and controls. Significant increases in numbers of CD34 cells were not detected. Of importance, the cloning efficiency of CD34 cells increased from 1.7% prior to therapy to a peak at 18.7% (P=.003). In conclusion, HAART normalized CD34 cell function...

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...... of the antidiabetics metformin or glitazones to high dose recombinant human growth hormone therapy or switching antiretroviral regimen. When looking at the effect of switching therapy, focus has been addressed to protease inhibitor (PI) based regimens, as PI was the first component of HAART recognized to be correlated...

Association Between the Occurrence of Adverse Drug Events and Modification of First-Line Highly Active Antiretroviral Therapy in Ghanaian HIV Patients.

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Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Yankey, Barbara A; Dodoo, Alexander N O

2016-11-01

Patients initiated on highly active antiretroviral therapy (HAART) generally remain on medication indefinitely. A modification in the HAART regimen may become necessary because of possible acute or chronic toxicities, concomitant clinical conditions, development of virological failure or the advent of adverse drug events. The study documents adverse drug events of HIV-positive Ghanaian patients with HAART modifications. It also investigates the association between documented adverse drug events and HAART modification using an unmatched case-control study design. The study was conducted in the Fevers Unit of the Korle Bu Teaching Hospital and involved patients who attended the HIV Care Clinic between January 2004 and December 2009. Data from 298 modified therapy patients (cases) were compared with 298 continuing therapy patients (controls) who had been on treatment for at least 1 month before the end of study. Controls were sampled from the same database of a cohort of HIV-positive patients on HAART, at the time a case occurred, in terms of treatment initiation ±1 month. Data were obtained from patients' clinical folders and the HIV clinic database linked to the pharmacy database. The nature of the documented adverse drug events of the cases was described and the association between the documented adverse drug events and HAART modification was determined by logistic regression with reported odds ratios (ORs) and their 95 % confidence interval (CI). Among the 298 modified therapy patients sampled in this study, 52.7 % of them had at least one documented adverse drug event. The most documented adverse drug event was anaemia, recorded in 18.5 % of modified therapy patients, all of whom were on a zidovudine-based regimen. The presence of documented adverse drug events was significantly associated with HAART modification [adjusted OR = 2.71 (95 % CI 2.11-3.48), p < 0.001]. Among HIV patients on HAART, adverse drug events play a major role in treatment

Prevalence of thrombocytopenia before and after initiation of HAART among HIV infected patients at black lion specialized hospital, Addis Ababa, Ethiopia: a cross sectional study.

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Woldeamanuel, Gashaw Garedew; Wondimu, Diresibachew Haile

2018-01-01

Hematological abnormalities are common in HIV positive patients. Of these, thrombocytopenia is a known complication which has been associated with a variety of bleeding disorders. However, its magnitude and related factors have not been well-characterized in the era of highly active antiretroviral therapy (HAART) in Ethiopia. Therefore, this study aimed to assess the prevalence of thrombocytopenia before and after initiation of HAART among HIV positive patients attending Black Lion Specialized Hospital, Addis Ababa, Ethiopia. A cross sectional study was conducted from February to April 2017 in Black Lion Specialized Hospital, Addis Ababa, Ethiopia. A total of 176 patients on HAART were selected using simple random sampling techniques. Socio-demographic and clinical characteristics of the study patients were collected using structured questionnaire. Measurements of platelet counts and CD4 + T cell counts were made using Sysmex XT 2000i hematology analyzer and BD FACS Count CD4 analyzer, respectively. Statistical analysis of the data (Paired T- test and binary logistic regression) was done using SPSS version 20. P -value  18 years old) were enrolled in this study and had a mean age of 40.08 ± 9.38 years. There was significant increase in the mean values of platelet counts (218.44 ± 106.6 × 10 3 /μl vs 273.65 ± 83.8 × 10 3 /μl, p  < 0.001) after six months of HAART initiation compared to the baseline. Prevalence of thrombocytopenia before and after HAART initiation was 25 and 5.7% respectively. HIV patients whose CD4 counts < 200 Cells/μl were more likely to have thrombocytopenia than HIV patients whose CD4 count ≥350 Cells/μl. However, it was not statistically associated with prevalence of thrombocytopenia. This study has shown that the prevalence of thrombocytopenia after HAART initiation was decreased significantly. Based on our results, a number of study participants still had thrombocytopenia after initiation of HAART

Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review.

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Matthew Arentz

Full Text Available Use of antiretroviral therapy (ART during treatment of drug susceptible tuberculosis (TB improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB.We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events.Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR 3.4, 95% CI 1.6-7.4 and decreased likelihood of death (HR 0.4, 95% CI 0.3-0.6 during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm(3 and less than 50 cells/mm(3, and when correcting for drug resistance pattern.We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias.While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.

The cost-effectiveness of directly observed highly-active antiretroviral therapy in the third trimester in HIV-infected pregnant women.

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Caitlin J McCabe

Full Text Available BACKGROUND: In HIV-infected pregnant women, viral suppression prevents mother-to-child HIV transmission. Directly observed highly-active antiretroviral therapy (HAART enhances virological suppression, and could prevent transmission. Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy. METHODS AND FINDINGS: A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART, with women randomly assigned self-administered or directly observed antiretroviral therapy (DOT, or no HAART, in a series of Monte Carlo simulations. Our primary outcome was the quality-adjusted life expectancy in years (QALY of infants born to HIV-infected women, with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes. Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART. The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART; was highly cost-effective in the cohort as a whole (cost-utility ratio $14,233 per QALY; and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml. Results were stable in wide-ranging sensitivity analyses, with directly observed therapy cost-saving or highly cost-effective in almost all cases. CONCLUSIONS: Based on the best available data, programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner. Targeted use of DOT in pregnant women with high viral loads, who could otherwise receive self-administered HAART would be a cost-saving intervention. These projections should be tested with randomized clinical trials.

The cost-effectiveness of directly observed highly-active antiretroviral therapy in the third trimester in HIV-infected pregnant women.

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McCabe, Caitlin J; Goldie, Sue J; Fisman, David N

2010-04-13

In HIV-infected pregnant women, viral suppression prevents mother-to-child HIV transmission. Directly observed highly-active antiretroviral therapy (HAART) enhances virological suppression, and could prevent transmission. Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy. A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART, with women randomly assigned self-administered or directly observed antiretroviral therapy (DOT), or no HAART, in a series of Monte Carlo simulations. Our primary outcome was the quality-adjusted life expectancy in years (QALY) of infants born to HIV-infected women, with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes. Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART. The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART; was highly cost-effective in the cohort as a whole (cost-utility ratio $14,233 per QALY); and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml. Results were stable in wide-ranging sensitivity analyses, with directly observed therapy cost-saving or highly cost-effective in almost all cases. Based on the best available data, programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner. Targeted use of DOT in pregnant women with high viral loads, who could otherwise receive self-administered HAART would be a cost-saving intervention. These projections should be tested with randomized clinical trials.

Assessment of quality of life in HAART-treated HIV-positive subjects with body fat redistribution in Rwanda

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Crowther Nigel J

2007-09-01

Full Text Available Abstract Background The introduction of HAART has initially improved the quality of life (QoL of HIV-positive (HIV+ patients, however body fat redistribution (BFR and metabolic disorders associated with long-term HAART use may attenuate this improvement. As access to treatment improves in sub-Saharan Africa, the disfiguring nature of BFR (peripheral atrophy and/or central adiposity may deter treatment adherence and initiatives and decrease QoL. We examined the relationship between BFR and domains of QoL in HAART-treated HIV+ African men and women with (HIV+BFR, n = 50 and without (HIV+noBFR, n = 50 BFR in Rwanda. Results HIV+ subjects with BFR were less satisfied with their body image (4.3 ± 0.1 versus 1.5 ± 0.2; p 2 = 0.691; p = 0.009 and marital status was associated with psychological (r2 = 0.593; p = 0.019 and social relationships (r2 = 0.493; p = 0.007. CD4 count (r2 = 0.648; p = 0.003 and treatment duration (r2 = 0.453; p = 0.003 were associated with HIV HAART-specific domain of wellbeing. HIV+ Rwandan women with BFR were significantly more affected by abdominal adiposity (p Conclusion Body fat alterations negatively affect psychological and social domains of quality of life. These symptoms may result in stigmatization and marginalization mainly in HAART-treated African women, adversely affecting HAART adherence and treatment initiatives. Efforts to evaluate self-perceived body fat changes may improve patients' wellbeing, HAART adherence and treatment outcomes and contribute towards stability in quality of life continuum.

Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy

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Laura Pisarsky

2016-05-01

Full Text Available Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. Here, we demonstrate potent anti-angiogenic efficacy of the multi-kinase inhibitors nintedanib and sunitinib in a mouse model of breast cancer. However, after an initial regression, tumors resume growth in the absence of active tumor angiogenesis. Gene expression profiling of tumor cells reveals metabolic reprogramming toward anaerobic glycolysis. Indeed, combinatorial treatment with a glycolysis inhibitor (3PO efficiently inhibits tumor growth. Moreover, tumors establish metabolic symbiosis, illustrated by the differential expression of MCT1 and MCT4, monocarboxylate transporters active in lactate exchange in glycolytic tumors. Accordingly, genetic ablation of MCT4 expression overcomes adaptive resistance against anti-angiogenic therapy. Hence, targeting metabolic symbiosis may be an attractive avenue to avoid resistance development to anti-angiogenic therapy in patients.

Parkinsonism and AIDS: a clinical comparative study before and after HAART

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Ana Lucia Zuma de Rosso

2009-09-01

Full Text Available In 2002, after analyzing 28 HIV-positive patients with movement disorders we emphasized the decreasing not only of Parkinsonism but also of other involuntary movements in HIV patients in the last few years. The objective of this study is to compare the clinical results between HIV-positive patients with Parkinsonism before and after HAART. In 14 years (1986-1999 2,460 HIV-positive patients were seen in our Hospital 14 (0.6% of which presented with Parkinsonism. Eight years after (2000-2007 970 HIV positive patients were seen and only two (0.2% had Parkinsonism. We conclude that after the introduction of HAART there was an evident decrease in AIDS-related Parkinsonism.No ano de 2002, após analisarmos 28 pacientes HIV-positivos que apresentavam distúrbios do movimento, enfatizamos o declínio, não só do parkinsonismo, como também de outros movimentos involuntários em pacientes infectados pelo HIV nos últimos anos. O objetivo deste estudo é comparar os resultados clínicos entre pacientes HIV-positivos com parkinsonismo antes e depois da introdução do esquema HAART. Em 14 anos (1986-1999, 2.460 pacientes HIV-positivos foram avaliados em nosso Hospital dos quais 14 (0,6% apresentaram parkinsonismo. Nos oito anos seguintes (2000-2007, 970 pacientes HIV-positivos foram avaliados e somente dois (0,2% tinham parkinsonismo. Concluímos que após a introdução do esquema HAART houve evidente declínio do parkinsonismo secundário à AIDS.

Anterior segment and external ocular disorders associated with HIV infections in the era of HAART in Chiang Mai University Hospital, a prospective descriptive cross sectional study.

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Tassapol Singalavanija

Full Text Available Human immunodeficiency virus (HIV causes impairment to the human immune system which leads to immunocompromised conditions, including ocular complications. Several important HIV-associated disorders may involve the anterior segment, ocular surface, and adnexae organ such as dry eye, blepharitis which reduce quality of life of patients. In present, potent antiretroviral therapies HAART (highly active antiretroviral therapy has improved the length and quality of life which may lead to an increased prevalence of anterior segment ocular disorders. Hence, this study has been undertaken to identify the prevalence and associated factors of anterior segment and external ocular disorder in HIV infected patients in the era of HAART. A prospective descriptive cross sectional study was carried out in HIV positive patients conducted at the Department of Ophthalmology, Chiang Mai University Hospital, from February 2014 to October 2015. Detail history and ocular examination was carried out to examine for anterior segment and external ocular disorders. A total number of 363 patients were included for this prospective cross-sectional study. From the total of 363 patients, 123 patients had an anterior segment and external ocular disorder which account as the prevalence of 33.9%. The most common anterior segment manifestations was dry eye seen in 36 patients (9.9%, followed by posterior blepharitis (Meibomian gland dysfunction seen in 23 patients (6.3% and anterior blepharitis seen in 12 patients (3.3%. Other ocular complications included microvasculopathy, immune recovery uveitis, conjunctivitis, papilloma, anterior uveitis, corneal ulcer, nevus, trichiasis, molluscum contangiosum, Kaposi sarcoma, interstitial keratitis, conjunctival lymphangiectasia, dacryocystitis, vernal keratoconjunctivitis and eyelid penicilosis. In this study, the prevalance of anterior segment disorders was higher than in the preHAART era. Dry eye, blepharitis and uveitis were the top

HIV-1 infection and antiretroviral therapies: risk factors for osteoporosis and bone fracture.

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Ofotokun, Ighovwerha; Weitzmann, M Neale

2010-12-01

Patients with HIV-1 infection/AIDS are living longer due to the success of highly active antiretroviral therapy (HAART). However, serious metabolic complications including bone loss and fractures are becoming common. Understanding the root causes of bone loss and its potential implications for aging AIDS patients will be critical to the design of effective interventions to stem a tidal wave of fractures in a population chronically exposed to HAART. Paradoxically, bone loss may occur not only due to HIV/AIDS but also as a consequence of HAART. The cause and mechanisms driving these distinct forms of bone loss, however, are complex and controversial. This review examines our current understanding of the underlying causes of HIV-1 and HAART-associated bone loss, and recent findings pertaining to the relevance of the immuno-skeletal interface in this process. It is projected that by 2015 more than half of the HIV/AIDS population in the USA will be over the age of 50 and the synergy between HIV and/or HAART-related bone loss with age-associated bone loss could lead to a significant health threat. Aggressive antiresorptive therapy may be warranted in high-risk patients.

Year impact of highly active antiretroviral therapy on quality of life of ...

African Journals Online (AJOL)

Objective: The availability of highly active antiretroviral therapy (HAART) has resulted in a number of achievements as well as challenges. The aim of this study was to assess the influence of 48 weeks HAART of stavudine, lamivudine and nevirapine on the quality of life of HIVinfected Nigerians. Materials and Method: ...

Opportunistic infections in patients with aids admitted to an university hospital of the Southeast of Brazil Infecções oportunistas em pacientes com aids internados em um hospital universitário do sudeste do Brasil

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Vandack Nobre

2003-04-01

Full Text Available Opportunistic diseases in HIV-infected patients have changed since the introduction of highly active anti-retroviral therapy (HAART. This study aims at evaluating the frequency of associated diseases in patients with AIDS admitted to an university hospital of Brazil, before and after HAART. The medical records of 342 HIV-infected patients were reviewed and divided into two groups: group 1 comprised 247 patients before HAART and, group 2, 95 patients after HAART. The male-to-female rate dropped from 5:1 to 2:1for HIV infection. There was an increase in the prevalence of tuberculosis and toxoplasmosis, with a decrease in Kaposi's sarcoma, histoplasmosis and cryptococcosis. A reduction of in-hospital mortality (42.0% vs. 16.9%; p = 0.00002 has also occurred. An agreement between the main clinical diagnoses and autopsy findings was observed in 10 out of 20 cases (50%. Two patients with disseminated schistosomiasis and 2 with paracoccidioidomycosis are reported. Overall, except for cerebral toxoplasmosis, it has been noticed a smaller proportion of opportunistic conditions related to severe immunosuppression in the post HAART group. There was also a significant reduction in the in-hospital mortality, possibly reflecting improvement in the treatment of the HIV infection.O espectro das doenças oportunistas em pacientes com aids vem se modificando desde a introdução da terapia antiretroviral altamente eficaz (HAART. O objetivo deste estudo é o de avaliar o perfil das afecções oportunistas em pacientes com aids internados em um hospital universitário do Brasil, comparando os períodos pré e pós-utilização da terapia HAART. Para tanto, revisaram-se os prontuários médicos de 342 pacientes infectados pelo HIV, dividindo-os em dois grupos: grupo 1, composto de 247 pacientes pré-HAART e grupo 2, composto de 95 pacientes pós-HAART. A relação homem-mulher caiu de 5:1 para 2:1. Houve aumento da prevalência da tuberculose e da toxoplasmose, com

Differential improvement in survival among patients with AIDS after the introduction of HAART

OpenAIRE

2007-01-01

Abstract We explored changes in the survival of patients with AIDS (PWA) according to the availability of antiretroviral drugs (1994-2002). We tested whether changes in the hazard ratio of progression to death (HR) have been homogeneous among various groups of PWA. We included 4158 PWA diagnosed in Paris, notified to the French National Surveillance Institute by 2002. Four calendar periods were defined: monotherapy (1994-1995), bitherapy-HAART transition (1996), early HAART (19...

Improved Coinfection with Amphotropic Pseudotyped Retroviral Vectors

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Yuehong Wu

2009-01-01

Full Text Available Amphotropic pseudotyped retroviral vectors have typically been used to infect target cells without prior concentration. Although this can yield high rates of infection, higher rates may be needed where highly efficient coinfection of two or more vectors is needed. In this investigation we used amphotropic retroviral vectors produced by the Plat-A cell line and studied coinfection rates using green and red fluorescent proteins (EGFP and dsRed2. Target cells were primary human fibroblasts (PHF and 3T3 cells. Unconcentrated vector preparations produced a coinfection rate of ∼4% (defined as cells that are both red and green as a percentage of all cells infected. Optimized spinoculation, comprising centrifugation at 1200 g for 2 hours at 15∘C, increased the coinfection rate to ∼10%. Concentration by centrifugation at 10,000 g or by flocculation using Polybrene increased the coinfection rate to ∼25%. Combining the two processes, concentration by Polybrene flocculation and optimized spinoculation, increased the coinfection rate to 35% (3T3 or >50% (PHF. Improved coinfection should be valuable in protocols that require high transduction by combinations of two or more retroviral vectors.

A randomized controlled trial comparing the effects of counseling and alarm device on HAART adherence and virologic outcomes.

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Michael H Chung

2011-03-01

Full Text Available Behavioral interventions that promote adherence to antiretroviral medications may decrease HIV treatment failure. Antiretroviral treatment programs in sub-Saharan Africa confront increasing financial constraints to provide comprehensive HIV care, which include adherence interventions. This study compared the impact of counseling and use of an alarm device on adherence and biological outcomes in a resource-limited setting.A randomized controlled, factorial designed trial was conducted in Nairobi, Kenya. Antiretroviral-naïve individuals initiating free highly active antiretroviral therapy (HAART in the form of fixed-dose combination pills (d4T, 3TC, and nevirapine were randomized to one of four arms: counseling (three counseling sessions around HAART initiation, alarm (pocket electronic pill reminder carried for 6 months, counseling plus alarm, and neither counseling nor alarm. Participants were followed for 18 months after HAART initiation. Primary study endpoints included plasma HIV-1 RNA and CD4 count every 6 months, mortality, and adherence measured by monthly pill count. Between May 2006 and September 2008, 400 individuals were enrolled, 362 initiated HAART, and 310 completed follow-up. Participants who received counseling were 29% less likely to have monthly adherence <80% (hazard ratio [HR] = 0.71; 95% confidence interval [CI] 0.49-1.01; p = 0.055 and 59% less likely to experience viral failure (HIV-1 RNA ≥5,000 copies/ml (HR 0.41; 95% CI 0.21-0.81; p = 0.01 compared to those who received no counseling. There was no significant impact of using an alarm on poor adherence (HR 0.93; 95% CI 0.65-1.32; p = 0.7 or viral failure (HR 0.99; 95% CI 0.53-1.84; p = 1.0 compared to those who did not use an alarm. Neither counseling nor alarm was significantly associated with mortality or rate of immune reconstitution.Intensive early adherence counseling at HAART initiation resulted in sustained, significant impact on adherence and

Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

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Halasa, Salaheldin; Dickinson, Eva

2014-02-01

From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

Early severe morbidity and resource utilization in South African adults on antiretroviral therapy

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Meintjes Graeme A

2009-12-01

Full Text Available Abstract Background High rates of mortality and morbidity have been described in sub-Saharan African patients within the first few months of starting highly active antiretroviral therapy (HAART. There is limited data on the causes of early morbidity on HAART and the associated resource utilization. Methods A cross-sectional study was conducted of medical admissions at a secondary-level hospital in Cape Town, South Africa. Patients on HAART were identified from a register and HIV-infected patients not on HAART were matched by gender, month of admission, and age group to correspond with the first admission of each case. Primary reasons for admission were determined by chart review. Direct health care costs were determined from the provider's perspective. Results There were 53 in the HAART group with 70 admissions and 53 in the no-HAART group with 60 admissions. The median duration of HAART was 1 month (interquartile range 1-3 months. Median baseline CD4 count in the HAART group was 57 × 106 cells/L (IQR 15-115. The primary reasons for admission in the HAART group were more likely to be due to adverse drug reactions and less likely to be due to AIDS events than the no-HAART group (34% versus 7%; p Conclusions Causes of early morbidity are different and more complex in HIV-infected patients on HAART. This results in greater resource utilization of diagnostic and therapeutic services.

Risk Perception and sexual risk behaviors among HIV-positive men on antiretroviral therapy.

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Remien, Robert H; Halkitis, Perry N; O'Leary, Ann; Wolitski, Richard J; Gómez, Cynthia A

2005-06-01

There are reports of increased sexual risk behavior among people on highly active antiretroviral therapy (HAART) due to beliefs about risk of HIV transmission when on HAART. In a cross-sectional study (Seropositive Urban Men's Study), we examined the relationship between risk perception and sexual risk behavior among sexually active, culturally diverse HIV positive men who have sex with men (N = 456). Less than twenty-five percent engaged in unprotected anal sex (either with an HIV negative, or unknown-status partner, or an HIV positive partner) within the past 3 months. Most men believed there was significant health risk (to partner or self) associated with unprotected sex when on HAART. There was no increased risk behavior associated with being on HAART, although the perception of negative health consequences, including HIV transmission, when on HAART was significantly lower for the relatively small subset of men who reported unprotected sex. Prevention strategies need to be tailored to address risk perception associated with HAART.

Contracepção hormonal e anti-retrovirais em mulheres infectadas pelo HIV Hormonal contraception and antiretroviral therapy among HIV-infected women

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Eliana Amaral

2006-11-01

Full Text Available Há controvérsia sobre a relação entre o uso de contraceptivos hormonais e o risco de adquirir o vírus da imunodeficiência humana (HIV, e pouco se sabe sobre os efeitos da contracepção hormonal em mulheres infectadas (efeitos colaterais, distúrbios menstruais, progressão da doença, interações com terapias anti-retrovirais. O objetivo deste artigo foi revisar os dados disponíveis quanto à vulnerabilidade ao HIV e à sua transmissibilidade na vigência do uso de contraceptivos hormonais bem como as conseqüências potenciais do uso desses contraceptivos por mulheres HIV-positivas sob terapia anti-retroviral (TARV, com ênfase nas interações medicamentosas. Concluiu-se que ainda não é possível elaborar recomendações, baseadas em evidências, sobre a contracepção hormonal em mulheres portadoras do HIV sob TARV. Assim, os infectologistas e os ginecologistas devem estar atentos às interações potenciais que possam representar aumento de efeitos adversos, individualizando a orientação sobre os esteróides contraceptivos, suas doses e vias de administração, considerando a TARV em uso.There is much controversy regarding the realtionship between the use of hormonal contraceptives and the risk of acquiring human immunodeficiency virus (HIV, and little is known about the effects of hormonal contraception in HIV-infected women (adverse events, menstrual disorders, disease progression, antiretroviral therapy interactions. The aim of the present study was to review available data regarding HIV vulnerability and transmission associated with hormonal contraceptives and the use of these contraceptives by women on antiretroviral therapy, with emphasis on drug interactions. In conclusion, it was not possible to offer evidence-based recommendations for the use of hormonal contraceptives among HIV-infected women under antiretroviral therapy. Infectious disease specialists and gynecologists providing care should be cautious about potential

Isoniazid-resistant Mycobacterium kansasii in an HIV-positive patient, and possible development of immune reconstitution inflammatory syndrome after initiation of highly active antiretroviral therapy: case report

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A. Despotovic

2016-01-01

Full Text Available Non-tuberculous mycobacteria are rare but important causes of infection in HIV-positive individuals. A 28-year-old HIV-positive male presented with a high fever, non-productive cough, right subcostal pain, splenomegaly, a very low CD4 count, elevated C-reactive protein and erythrocyte sedimentation rate, and a normal white blood cell count. The suspicion of tuberculosis (TB was very high, and sputum samples were positive for acid-fast bacilli. Standard quadruple anti-TB therapy was initiated, but once culture of the sample revealed Mycobacterium kansasii, pyrazinamide was withdrawn. Highly active antiretroviral therapy (HAART was initiated soon after, consisting of abacavir/lamivudine and efavirenz. The patient's general condition deteriorated 2 weeks after HAART initiation, which could have been due to the development of immune reconstitution inflammatory syndrome (IRIS. The patient recovered and was discharged in good condition. However, the results of resistance testing of the isolated organism arrived after discharge, and showed isoniazid and streptomycin resistance. This is the first case report of M. kansasii infection from Serbia and shows the difficulties encountered during the course of treatment.

Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

Science.gov (United States)

Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

2013-01-01

Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from 38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

Graves' Disease as a Manifestation of Immune Reconstitution in HIV-Infected Individuals after Initiation of Highly Active Antiretroviral Therapy

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Samad Rasul

2011-01-01

Full Text Available Graves' disease after the initiation of highly active antiretroviral therapy (HAART in certain HIV-1-infected individuals has been described as an immune reconstitution inflammatory syndrome (IRIS. This phenomenon should be suspected in individuals who present with clinical deterioration and a presentation suggestive of hyperthyroidism despite good virological and immunological response to HAART. Signs and symptoms of hyperthyroidism may be discrete or overt and typically develop 8–33 months after initiating therapy. One to two percent of HIV-infected patients can present with overt thyroid disease. Relatively few cases of Graves' IRIS have been reported in the literature to date. We describe four cases of Graves' IRIS in HIV-infected patients who were started on HAART therapy.

Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia – case report

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Blennow Kaj

2006-09-01

Full Text Available Abstract Background Since the introduction of HAART the incidence of HIV dementia has declined and HAART seems to improve neurocognitive function in patients with HIV dementia. Currently, HIV dementia develops mainly in patients without effective treatment, though it has also been described in patients on HAART and milder HIV-associated neuropsychological impairment is still frequent among HIV-1 infected patients regardless of HAART. Elevated cerebrospinal fluid (CSF levels of markers of neural injury and immune activation have been found in HIV dementia, but neither of those, nor CSF HIV-1 RNA levels have been proven useful as diagnostic or prognostic pseudomarkers in HIV dementia. Case presentation We report a case of HIV dementia (MSK stage 3 in a 57 year old antiretroviral naïve man who was introduced on zidovudine, lamivudine and ritonavir boosted indinavir, and followed with consecutive lumbar punctures before and after two and 15 months after initiation of HAART. Improvement of neurocognitive function was paralleled by normalisation of CSF neural markers (NFL, Tau and GFAP levels and a decline in CSF and serum neopterin and CSF and plasma HIV-1 RNA levels. Conclusion The value of these CSF markers as prognostic pseudomarkers of the effect of HAART on neurocognitive impairment in HIV dementia ought to be evaluated in longitudinal studies.

CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1–infected individuals

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Ahuja, Sunil K; Kulkarni, Hemant; Catano, Gabriel; Agan, Brian K; Camargo, Jose F; He, Weijing; O'Connell, Robert J; Marconi, Vincent C; Delmar, Judith; Eron, Joseph; Clark, Robert A; Frost, Simon; Martin, Jeffrey; Ahuja, Seema S; Deeks, Steven G; Little, Susan; Richman, Douglas; Hecht, Frederick M; Dolan, Matthew J

2008-01-01

The basis for the extensive variability seen in the reconstitution of CD4+ T cell counts in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) is not fully known. Here, we show that variations in CCL3L1 gene dose and CCR5 genotype, but not major histocompatibility complex HLA alleles, influence immune reconstitution, especially when HAART is initiated at <350 CD4+ T cells/mm3. The CCL3L1-CCR5 genotypes favoring CD4+ T cell recovery are similar to those that blunted CD4+ T cell depletion during the time before HAART became available (pre-HAART era), suggesting that a common CCL3L1-CCR5 genetic pathway regulates the balance between pathogenic and reparative processes from early in the disease course. Hence, CCL3L1-CCR5 variations influence HIV pathogenesis even in the presence of HAART and, therefore, may prospectively identify subjects in whom earlier initiation of therapy is more likely to mitigate immunologic failure despite viral suppression by HAART. Furthermore, as reconstitution of CD4+ cells during HAART is more sensitive to CCL3L1 dose than to CCR5 genotypes, CCL3L1 analogs might be efficacious in supporting immunological reconstitution. PMID:18376407

A STUDY OF DYSLIPIDAEMIA IN HIV PATIENTS RECEIVING HAART

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Chepuri Venkata Ravikumar

2018-02-01

Full Text Available BACKGROUND Human Immunodeficiency Virus (HIV was discovered in 1986 in Chennai (India amongst female sex workers by Dr. Suniti Solomon. Since then, HIV has spread to all parts of the country from the high-risk group to the antepartum population in many states at an alarming rate. The prevalence of dyslipidaemia and other risk factors for cardiovascular disease is significant in HIV/AIDS patients receiving highly active antiretroviral therapy (HAART, ranging from 20% to 80%. In view of the high prevalence of dyslipidaemia and the increased risk for cardiovascular diseases among patients with HIV/AIDS, this is a matter of concern for public health. MATERIALS AND METHODS 143 patients who had been receiving HAART for a minimum of two years from Rajiv Gandhi Institute of Medical Sciences, Kadapa, during the period of January 2015 to September 2016 were studied. They were divided into 4 regimens groups 1 TEL (Tenofovir, Efavirenz, Lamivudine 2 TLAR (Tenofovir, Lamivudine, Atazanavir, Ritonavir 3 ZLE (Zidovudine, Lamivudine, Efavirenz 4 ZLN (Zidovudine, Lamivudine, Nevirapine. Detailed history, demographic data, anthropometric measurements, serum lipid profile obtained and analysed. RESULTS Out of 143 patients, 90 (62.9% were males and 53 (37.1% were females. 68 (47.6% were in the 30-39 years age group accounted for maximum percentage of groups. Based on BMI only 3 (2.1% were obese, 24 (16.8% were of overweight. WaistHip ratio was abnormal in 117 (81.8% and 26 (18.2% were normal. The mean values for patients on TEL regimen are TC is 195.4 mg%, LDL 122.1 mg%, HDL 34.96 mg%, TG 194.02 mg% and TC/HDL is 5.5714. In patients treated with TLAR regimen the mean values of TC are 172.15 mg%, LDL 99.15 mg %, HDL 36.35 mg%, TG 183.35 mg% and TC/HDL is 4.8. In patients treated with ZLE regimen, TC is 201.64 mg%, LDL 123.27 mg%, HDL 35.68 mg%, TG 212.27 mg% and TC/HDL is 5.6364. In patients treated with ZLN regimen, TC is 162.1 mg%, LDL 91.94 mg%, HDL 35.98 mg%, TG

Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study

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Babiker, Abdel G; Emery, Sean; Fätkenheuer, Gerd; Gordin, Fred M; Grund, Birgit; Lundgren, Jens D; Neaton, James D; Pett, Sarah L; Phillips, Andrew; Touloumi, Giota; Vjecha, Michael J

2012-01-01

Background 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 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 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. Purpose In this article, we outline the rationale and methods of the Strategic Timing of AntiRetroviral Treatment (START) study, an ongoing multicenter international trial designed to assess the risks and benefits of initiating ART earlier than is currently practiced. We also describe some of the challenges encountered in the design and implementation of the study and how these challenges were addressed. Methods A total of 4000 study participants who are HIV type 1 (HIV-1) infected, ART naïve with CD4 count > 500 cells/μL are to be randomly allocated in a 1:1 ratio to start ART immediately (early ART) or defer treatment until CD4 count is AIDS, SNA, or death. The study had a pilot phase to establish feasibility of accrual, which was set as the enrollment of at least 900 participants in the first year. Results Challenges encountered in the design and implementation of the study included the limited amount of data on the risk of a major component of the primary endpoint (SNA) in the study population, changes in treatment guidelines when the pilot phase was well underway, and the complexities of conducting the trial in a geographically wide

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

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Sinha, Sanjeev; Shekhar, Rahul C; Singh, Gurjeet; Shah, Nipam; Ahmad, Hafiz; Kumar, Narendra; Sharma, Surendra K; Samantaray, J C; Ranjan, Sanjai; Ekka, Meera; Sreenivas, Vishnu; Mitsuyasu, Ronald T

2012-07-31

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. 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. 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. Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. CTRI/2011/12/002260.

Disclosure of HIV status and its impact on the loss in the follow-up of HIV-infected patients on potent anti-retroviral therapy programs in a (post- conflict setting: A retrospective cohort study from Goma, Democratic Republic of Congo.

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Pierre Zalagile Akilimali

Full Text Available The study aimed to identify the impact of non-disclosure of HIV status on the loss to follow-up (LTFU of patients receiving anti-retroviral therapy.A historic cohort of HIV patients from 2 major hospitals in Goma, Democratic Republic of Congo was followed from 2004 to 2012. LTFU was defined as not taking an ART refill for a period of 3 months or longer since the last attendance, and had not yet been classified as 'dead' or 'transferred-out'. Kaplan-Meier plots were used to determine the probability of LTFU as a function of time as inclusive of the cohort. The log-rank test was used to compare survival curves based on determinants. Cox proportional hazard modeling was used to measure predictors of LTFU from the time of treatment induction until December 15th, 2012 (the end-point.The median follow-up time was 3.99 years (IQR = 2.33 to 5.59. Seventy percent of patients had shared their HIV status with others (95% CI: 66.3-73.1. The proportion of LTFU was 12% (95%CI: 9.6-14.4. Patients who did not share their HIV status (Adjusted HR 2.28, 95% CI 1.46-2.29, patients who did not live in the city of Goma (Adjusted HR 1.97, 95% CI 1.02-3.77, and those who attained secondary or higher education level (Adjusted HR 1.60, 95% CI 1.02-2.53 had a higher hazard of being LTFU.This study shows the relationship between the non-disclosure HIV status and LTFU. Healthcare workers in similar settings should pay more attention to clients who have not disclosed their HIV status, and to those living far from health settings where they receive medication.

A systematic review of anti-thrombotic therapy in epistaxis.

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Musgrave, K M; Powell, J

2016-12-01

There is limited guidance available to clinicians regarding the management of antithrombotic therapy during epistaxis, whilst there has been an increase in the use of anticoagulation and antiplatelet therapy. In addition, the introduction of direct oral anticoagulants (DOACs), such as dabigatran and rivaroxaban, over the last decade has significantly increased the complexity of managing the anticoagulated epistaxis patient. We undertook a systemic literature review investigating potential management strategies for each class of anti-thrombotic therapy during epistaxis. A PubMED and Cochrane Library search was performed on 10/03/16 using, but not limited to, the search terms epistaxis, nosebleed, nose bleeding, nasal haemorrhage, nasal bleeding AND each of the following search terms: antithrombotic, anticoagulant, antiplatelet, aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, apixaban and tranexamic acid. This yielded 3815 results, of which 29 were considered relevant. Other sources such as national and international guidelines related to the management of anti-thrombotics were also utilised. We present the findings related to the management of each class of anti-thrombotic therapy during epistaxis. Overall we found a lack of evidence regarding this topic and further high quality research is needed. This is an area growing in complexity and the support of colleagues in Haematology and Cardiology is increasingly important.

Preliminary investigation of adherence to antiretroviral therapy ...

African Journals Online (AJOL)

Treatment of HIV with highly active antiretroviral therapy (HAART) has resulted in declining morbidity and mortality rates from HIV-associated diseases, but concerns regarding access and adherence are growing. To determine the adherence level and the reasons for non-adhering to antiretroviral therapy (ART) among ...

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...

immunological profiles in hiv positive patients following haart

African Journals Online (AJOL)

2014-08-01

Aug 1, 2014 ... undetectable viraemia); a recovery of CD4+ cells, a decrease in IL-10 (though it remained high for many patients ... A successful HAART results in CD4+ cells recovery, drop in viraemia and IL-10 with up-regulation of Th1 ... necrosis factor family (can induce cell death among other many functions, or ...

Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy

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Bernaschi Massimo

2009-10-01

Full Text Available Abstract Background The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART. Results Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy. In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.

Is anti-platelet therapy interruption a real clinical issue? Its implications in dentistry and particularly in periodontics

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Kumar A

2009-01-01

Full Text Available The use of anti-platelet therapy has reduced the mortality and morbidity of cardiovascular disease remarkably. A considerable number of patients presenting before a dentist or periodontist give a history of anti-platelet therapy. A clinical dilemma whether to discontinue the anti-platelet therapy or continue the same always confronts the practitioner. Diverse opinions exist regarding the management of such patients. While one group of researchers advise continuation of anti-platelet therapy rather than invite remote, but possible, thromboembolic events, another group encourages discontinuation for variable periods. This study aims at reviewing the current rationale of anti-platelet therapy and the various options available to a clinician, with regard to the management of a patient under anti-platelet therapy. Current recommendations and consensus favour no discontinuation of anti-platelet therapy. This recommendation, however, comes with a rider to use caution and consider other mitigating factors as well. With a large number of patients giving a history of anti-platelet therapy, the topic is of interest and helps a clinician to arrive at a decision.

Gender difference in health related quality of life and associated factors among people living with HIV/AIDS attending anti-retroviral therapy at public health facilities, western Ethiopia: comparative cross sectional study.

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Gebremichael, Delelegn Yilma; Hadush, Kokeb Tesfamariam; Kebede, Ermiyas Mulu; Zegeye, Robel Tezera

2018-04-23

Though HIV/AIDS has multidimensional consequences on quality of life, there is a gap in measuring and monitoring health related quality of life of HIV/AIDS patients. Hence, this study intended to measure health related quality of life domains and associated determinants among people living with HIV/AIDS in western Ethiopia. A comparative cross-sectional study was conducted among 520 HIV/AIDS patients on anti-retroviral therapy in public health facilities in West Shoa Zone, Western Ethiopia from April to May, 2016. Participants were selected using simple random sampling method. Quality of life was measured using WHOQOL-HIV BREF and depression was assessed using Beck Depression Inventory, Second Edition (BDI-II). Data were analyzed using SPSS version 22. An independent sample t-test was used to compare quality of life domains between men and women and logistic regression analysis was used to determine independent predictors. Females had significantly lower quality of life in physical, psychological, independence and environmental domains as compared with males except social relationship and spiritual domains. Depressed HIV patients had significantly lower quality of life in all domains as compared with HIV infected patients without depression in both genders. Malnutrition and anemia were significantly associated with poor physical, psychological, independence and environmental domains. Anemic women had 1.9 times lower independence quality of life compared with women who had no anemia (AOR = 1.9, 95%CI: 1.4, 3.5). Tuberculosis was also predictor of physical, psychological, independence and social domains in both genders. TB/HIV co-infected females had 2.0 times poorer environmental health compared to only HIV infected females (AOR = 2.0, 95%CI: 1.2, 3.5). Family support, education and occupation were also independent significant predictors of QOL domains in both genders. In females, residence was significantly associated with independence (AOR = 1.8, 95%CI

[Treatment of HIV infection from the neurologic viewpoint. Therapy must reach the brain].

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von Giesen, H J; Köller, H; Arendt, G

2002-04-09

An effective highly active antiretroviral therapy (HAART) can prevent the manifestation of HIV-1-associated encephalopathy. Also, HIV-1-associated minor cognitive/motor deficits--an early form of HIV-1-associated dementia--are improved. Clinically manifest HIV-1-associated encephalopathy is an indication for HAART treatment, irrespective of immune status. To date, minor cognitive and/or motor deficits in the presence of good immune status have not been identified as an indication for HAART treatment. Any CNS-effective treatment should be based on either zidovudine or stavudine, since these substances readily enter the CSF; however, NNRTI can also be applied. Side effects of HAART on the central and peripheral nervous system, as well as interactions with known neurological medicaments must be taken into account.

Dynamics of T-cell subsets and their relationship with oral and systemic opportunistic infections in HIV/AIDS patients during the first year of HAART in Guangxi, China.

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Zhang, Linlin; Huang, Yuxiao; Liu, Zhenmin; Liu, Wei; Qin, Qi; Tao, Renchuan

2015-07-01

To analyze the dynamic changes in Th1, Th2, Tc1, and Tc2 of HIV/AIDS patients during the first year of highly active antiretroviral therapy (HAART) and to explore their relationship with oral and systemic opportunistic infections, a cohort study was carried out among HIV/AIDS patients in Guangxi, China. Ninety HIV/AIDS patients and 30 healthy controls (HC) were included. The enrolled HIV/AIDS patients were examined at baseline and after 3, 6, and 12 months of HAART. On each visit, oral and systemic opportunistic infections were recorded, oral Candida load and plasma viral load (VL) were counted, differential T-cell counts and flow cytometric analysis of T-cell subsets were performed. During the first year of HAART, the total number of opportunistic infections decreased steadily with the change in oral candidiasis (OC) most representatively. A significant Th1→Th2 switch (Th1/Th2 ratio 0.23 ± 0.12, HC 1.45 ± 0.38) and slight Tc1→Tc2 shift (Tc1/Tc2 ratio 0.93 ± 0.29, HC 1.13 ± 0.33) were found at baseline, and both received slow mitigation after HAART. LgCFU and clinical OC were correlated positively with both LgVL and clinical stage (P Candida load could be useful clinical markers in the evaluation of HIV/AIDS patients. Th1 may play an important role against oral and systemic opportunistic infections. Tc1 and Tc2 both showed positive roles in the control of viremia without HAART. J. Med. Virol. 87:1158-1167, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Absence of transmission from HIV-infected individuals with HAART to their heterosexual serodiscordant partners.

Science.gov (United States)

Del Romero, Jorge; Río, Isabel; Castilla, Jesús; Baza, Begoña; Paredes, Vanessa; Vera, Mar; Rodríguez, Carmen

2015-12-01

Further studies are needed to evaluate the level of effectiveness and durability of HAART to reduce the risk of HIV sexual transmission in serodiscordant couples having unprotected sexual practices. A cross-sectional study was conducted with prospective cohort of heterosexual HIV serodiscordant couples where the only risk factor for HIV transmission to the uninfected partner (sexual partner) was the sexual relationship with the infected partner (index case). HIV prevalence in sexual partners at enrolment and seroconversions in follow-up were compared by antiretroviral treatment in the index partner, HIV plasma viral load in index cases and sexual risk exposures in sexual partners. In each visit, an evaluation of the risks for HIV transmission, preventive counselling and screening for genitourinary infections in the sexual partner was performed, as well as the determination of the immunological and virological situation and antiretroviral treatment in the index case. At enrolment no HIV infection was detected in 202 couples where the index case was taking HAART. HIV prevalence in sexual partners was 9.6% in 491 couples where the index case was not taking antiretroviral treatment (p<0.001). During follow-up there was no HIV seroconversion among 199 partners whose index case was taking HAART, accruing 7600 risky sexual exposures and 85 natural pregnancies. Among 359 couples whose index case was not under antiretroviral treatment, over 13,000 risky sexual exposures and 5 HIV seroconversions of sexual partners were recorded. The percentage of seroconversion among couples having risky sexual intercourse was 2.5 (95% confidence interval [CI]: 1.1-5.6) when the index case did not undergo antiretroviral treatment and zero (95% CI: 0-3.2) when the index case received HAART. The risk of sexual transmission of HIV from individuals with HAART to their heterosexual partners can become extremely low. Copyright © 2014. Published by Elsevier España, S.L.U.

Experiences and perceptions of patients with 100% adherence to highly active antiretroviral therapy: a qualitative study.

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Sidat, Mohsin; Fairley, Christopher; Grierson, Jeffrey

2007-07-01

A decade has passed since the introduction of highly active antiretroviral therapy (HAART) as standard of care for HIV/AIDS patients. The success of HAART is largely dependent on almost 100% adherence to it. In this study our primary aim was to understand from patients' own perspectives and experiences what resulted in them having 100% adherence to HAART. Thus, we purposefully recruited for in-depth interviews 10 participants (7 men and 3 women) with 100% adherence to HAART (>/=6 months previous to the interviews). All interviews were transcribed verbatim and analyzed by using Giorgi's phenomenological analysis approach. The following issues emerged from the analysis: readiness to go on HAART; HAART viewed as a life-line; maintenance of 100% adherence related with willingness to live longer and healthier; optimal ongoing patient-physician relationship, better coping and/or lack of perceived side effects; and improvements in clinical condition as well as in CD4 T-cells count and viral load reinforced the motivation to continue 100% adherence. The study findings should be helpful for health professionals caring for HIV-infected individuals on HAART.

Acute retroviral syndrome in Slovenian patients infected with HIV

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Mateja Pirš

2005-06-01

Full Text Available Background: Two to six weeks after primary infection with HIV 50 to 90 percent of patients develop an acute retroviral syndrome which usually presents with mononucleosis or flu-like illness. Due to nonspecific symptoms ARS is frequently misdiagnosed.Patients and methods: Data of Slovenian patients with acute retroviral syndrome is shown, as well as their symptoms, approaches to management and diagnostic particularities of primary HIV infection.Conclusions: The combination of particular symptoms and epidemiological data should lead us to consider the possibility of an early HIV infection.

Immune restoration in the context of HAART | Martin | Southern ...

African Journals Online (AJOL)

HAART induces a sustained effective suppression of HIV replication in most patients and leads to a preservation or restoration of immune function. The restoration of an impaired immune system is assessed by clinical parameters, immunological changes which can be measured in the laboratory and a marked reduction in ...

Eye Complications of Acquired Immune Deficiency Syndrome (AIDS ...

African Journals Online (AJOL)

Skoludek_R

The introduction of highly active anti-retroretroviral therapy (HAART) has changed the epidemiology of AIDS from ... Diagnosis and treatment of anterior segment disorders ... Carbamazepine 200 mg every night. .... AIDS and cancer in Africa.

MULTIFOCAL RETINAL INFILTRATES WITH PHLEBITIS AND OPTIC NEUROPATHY IN AN HIV-POSITIVE PEDIATRIC PATIENT.

Science.gov (United States)

Kasi, Sundeep K; Vora, Robin A; Martin, Taliva; Cunningham, Emmett T

2015-01-01

To describe an unusual presentation of bilateral HIV-associated multifocal retinal infiltrates with phlebitis and optic neuropathy in a pediatric patient from Zimbabwe, Africa. Retrospective case report of a 15-year-old boy from Zimbabwe, Africa. The patient was found to have bilateral vitritis, multifocal retinitis with phlebitis, and optic neuropathy in the setting of previously unrecognized HIV infection. Vision improved and the clinical findings resolved after treatment with intravenous corticosteroids and highly active retroviral therapy (HAART). The authors describe the occurrence and treatment of bilateral, HIV-associated multifocal retinal infiltrates with phlebitis and HIV-associated optic neuropathy in a pediatric patient from Zimbabwe, Africa.

New Approaches for Quantitating the Inhibition of HIV-1 Replication by Antiviral Drugs in vitro and in vivo

Science.gov (United States)

McMahon, Moira A.; Shen, Lin; Siliciano, Robert F.

2014-01-01

Purpose of review With highly active anti-retroviral therapy (HAART), HIV-1 infection has become a manageable lifelong disease. Developing optimal treatment regimens requires understanding how to best measure anti-HIV activity in vitro and how drug dose response curves generated in vitro correlate with in vivo efficacy. Recent findings Several recent studies have indicated that conventional multi-round infectivity assays are inferior to single cycle assays at both low and high levels of inhibition. Multi-round infectivity assays can fail to detect subtle but clinically significant anti-HIV activity. The discoveries of the anti-HIV activity of the hepatitis B drug entecavir and the herpes simplex drug acyclovir were facilitated by single round infectivity assays. Recent studies using a single round infectivity assay have shown that a previously neglected parameter, the dose response curve slope, is an extremely important determinant of antiviral activity. Some antiretroviral drugs have steep slopes that result in extraordinary levels of antiviral activity. The instantaneous inhibitory potential (IIP), the log reduction in infectivity in a single round assay at clinical drug concentrations, has been proposed as a novel index for comparing antiviral activity. Summary Among in vitro measures of antiviral activity, single round infection assays have the advantage of measure instantaneous inhibition by a drug. Re-evaluating the antiviral activity of approved HIV-1 drugs has shown that the slope parameter is an important factor in drug activity. Determining the IIP by using a single round infectivity assay may provide important insights that can predict the in vivo efficacy of anti-HIV-1 drugs. PMID:19841584

Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART.

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Giuseppe Lapadula

Full Text Available Immunological non-response (INR despite virological suppression is associated with AIDS-defining events/death (ADE. Little is known about its association with serious non-AIDS-defining events (nADE.Patients highly-active antiretroviral therapy (HAART with 50.1221 patients were observed for a median of 3 (IQR: 1.3-6.1 years. Pre-HAART CD4+ were 77/μl (IQR: 28-142 and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387, but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9% infectious, 17.4% renal, 17.4% cardiovascular, 7% hepatic were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61 per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56. Older age (per year, HR 1.03; 95%CI: 1.01-1.05, hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7, a history of previous nADE (HR 2.16; 95%CI: 1.06-4.4 and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21 were other independent predictors of newly diagnosed nADE.Patients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.

Construction of retroviral recombinant containing human tissue ...

African Journals Online (AJOL)

USER

2010-03-29

Mar 29, 2010 ... Recombinant retroviral vector containing human tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) gene was ..... heavy metal ions, the protein could be express in an .... involves adhesion, degradation and movement. To.

Potential mechanisms for cell-based gene therapy to treat HIV/AIDS.

Science.gov (United States)

Herrera-Carrillo, Elena; Berkhout, Ben

2015-02-01

An estimated 35 million people are infected with HIV worldwide. Anti-retroviral therapy (ART) has reduced the morbidity and mortality of HIV-infected patients but efficacy requires strict adherence and the treatment is not curative. Most importantly, the emergence of drug-resistant virus strains and drug toxicity can restrict the long-term therapeutic efficacy in some patients. Therefore, novel treatment strategies that permanently control or eliminate the virus and restore the damaged immune system are required. Gene therapy against HIV infection has been the topic of intense investigations for the last two decades because it can theoretically provide such a durable anti-HIV control. In this review we discuss two major gene therapy strategies to combat HIV. One approach aims to kill HIV-infected cells and the other is based on the protection of cells from HIV infection. We discuss the underlying molecular mechanisms for candidate approaches to permanently block HIV infection, including the latest strategies and future therapeutic applications. Hematopoietic stem cell-based gene therapy for HIV/AIDS may eventually become an alternative for standard ART and should ideally provide a functional cure in which the virus is durably controlled without medication. Recent results from preclinical research and early-stage clinical trials support the feasibility and safety of this novel strategy.

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

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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

Enteropatógenos relacionados à diarréia em pacientes HIV que fazem uso de terapia anti-retroviral Enteropathogens relating to diarrhea in HIV patients on antiretroviral therapy

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Áurea Regina Telles Pupulin

2009-10-01

Full Text Available A etiologia do processo diarréico na AIDS pode ser causada por vírus, bactérias, fungos, protozoários e helmintos, assim como pelo próprio HIV. Este trabalho avaliou enteropatogenos relacionados à diarréia em pacientes HIV que fazem uso de terapia anti-retroviral. Os métodos parasitológicos utilizados foram Faust, Hoffmann e Kinyoun. O isolamento e cultura dos fungos foram realizados conforme metodologia recomendada por NCCLS M27-A standard. A identificação das espécies de leveduras foi realizada através da reação em cadeia da polimerase. O isolamento de bactérias, foi feito em agar Mac Conkey e agar SS, a identificação das espécies através do Enterokit B (Probac do Brasil e métodos bioquímicos. Foram avaliados 49 pacientes, 44,9% apresentaram enteroparasitas, 48,1% Candida sp com 61,5% Candida albicans, 7,6% Candida sp e 30,7% Candida não- albicans. Foram isoladas bactérias de 72% dos pacientes, 49% Escherichia coli, 13% Salmonella parathyphi, Klebsiella sp ou Proteus e 6% Citrobacter freundii ou Yersinia sp. Houve alta prevalência de Candida sp nos pacientes HIV com diarréia e foram isoladas espécies não albicans cuja presença pode ser entendida como cúmplice ou causa da infecção.The etiology of the diarrheic process in AIDS may be caused by viruses, bacteria, fungi, protozoa or helminths, as well as HIV itself. This study evaluated enteropathogens relating to diarrhea in HIV patients who were on antiretroviral therapy. The parasitological methods used were Faust, Hoffmann and Kinyoun. Isolation and culturing of fungi were carried out in accordance with the methodology recommended by the NCCLS M27-A standard. The yeast species were identified using the polymerase chain reaction (PCR. Bacteria were isolated on MacConkey and SS agar and the species were identified using Enterokit B (Probac do Brasil and biochemical methods. Forty-nine patients were evaluated: 44.89% presented enteroparasites and 48.1% presented

Anaemia in HIV infected Nigerian children on HAART | Sadoh ...

African Journals Online (AJOL)

Annals of Biomedical Sciences ... Background: Most studies evaluating anaemia and associated factors in HIV infected children have been done on those that are HAART naïve. This study evaluated ... Data on age, gender, CD4 counts, CD4 percentage in those younger than 5years and tuberculosis status were obtained.

Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy

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Kirk, O.; Pedersen, C.; Cozzi-Leori, A.

2001-01-01

This study was designed to assess the influence of highly active antiretroviral therapy (HAART) on non-Hodgkin lymphoma (NHL) among patients infected with human immunodeficiency virus (HIV). Within EuroSIDA, a multicenter observational cohort of more than 8500 patients from across Europe......, the incidences of NHL and subtypes (Burkitt, immunoblastic, primary brain lymphoma [PBL], and other/unknown histology) were determined according to calendar time of follow-up, and for those who initiated HAART (> or =3 drugs) also time on HAART. Potential predictive factors of NHL were evaluated in Cox...

HIV-Antiretroviral Therapy Induced Liver, Gastrointestinal, and Pancreatic Injury

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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.

OFFICIAL MEDICATIONS FOR ANTI-TUMOR GENE THERAPY

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E. R. Nemtsova

2016-01-01

Full Text Available This is a review of modern literature data of official medications for anti-tumor gene therapy as well as of medications that finished clinical trials.The article discusses the concept of gene therapy, the statistical analysis results of initiated clinical trials of gene products, the most actively developing directions of anticancer gene therapy, and the characteristics of anti-tumor gene medications.Various delivery systems for gene material are being examined, including viruses that are defective in  replication (Gendicine™ and Advexin and oncolytic (tumor specific conditionally replicating viruses (Oncorine™, ONYX-015, Imlygic®.By now three preparations for intra-tumor injection have been introduced into oncology clinical practice: two of them – Gendicine™ and Oncorine™ have been registered in China, and one of them – Imlygic® has been registered in the USA. Gendicine™ and Oncorine™ are based on the wild type p53 gene and are designed for treatment of patients with head and neck malignancies. Replicating adenovirus is the delivery system in Gendicine™, whereas oncolytic adenovirus is the vector for gene material in Oncorine™. Imlygic® is based on the  recombinant replicating HSV1 virus with an introduced GM–CSF gene and is designed for treatment of  melanoma patients. These medications are well tolerated and do not cause any serious adverse events. Gendicine™ and Oncorine™ are not effective in monotherapy but demonstrate pronounced synergism with chemoand radiation therapy. Imlygic® has just started the post marketing trials.

Rates and reasons for early change of first HAART in HIV-1-infected patients in 7 sites throughout the Caribbean and Latin America.

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Carina Cesar

Full Text Available BACKGROUND: HAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%-70% of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region. METHODOLOGY: Antiretroviral-naïve patients >or= 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage. PRINCIPAL FINDINGS: Of 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31-44, and median CD4 count was 105 cells/uL (IQR, 38-200. Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI 15-17% and 28% (95% CI 27-29%, respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR = 1.7 (95% CI 1.1-2.6 and 2.1 (95% CI 1.7-2.5 comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1-1.5 for clinical AIDS at HAART initiation. The primary reason for change among HAART initiators were adverse events (14%, death (5.7% and failure (1.3% with specific toxicities varying among sites. After change, most patients remained in first line regimens. CONCLUSIONS: Adverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed and require

Rates and Reasons for Early Change of First HAART in HIV-1-Infected Patients in 7 Sites throughout the Caribbean and Latin America

Science.gov (United States)

Cesar, Carina; Shepherd, Bryan E.; Krolewiecki, Alejandro J.; Fink, Valeria I.; Schechter, Mauro; Tuboi, Suely H.; Wolff, Marcelo; Pape, Jean W.; Leger, Paul; Padgett, Denis; Madero, Juan Sierra; Gotuzzo, Eduardo; Sued, Omar; McGowan, Catherine C.; Masys, Daniel R.; Cahn, Pedro E.

2010-01-01

Background HAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%–70%) of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region. Methodology Antiretroviral-naïve patients > = 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals) was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage. Principal Findings Of 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31–44), and median CD4 count was 105 cells/uL (IQR, 38–200). Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI) 15–17%) and 28% (95% CI 27–29%), respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR) = 1.7 (95% CI 1.1–2.6) and 2.1 (95% CI 1.7–2.5) comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1–1.5) for clinical AIDS at HAART initiation). The primary reason for change among HAART initiators were adverse events (14%), death (5.7%) and failure (1.3%) with specific toxicities varying among sites. After change, most patients remained in first line regimens. Conclusions Adverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed

Central nervous system immune reconstitution inflammatory syndrome in AIDS: experience of a Mexican neurological centre.

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Guevara-Silva, Erik A; Ramírez-Crescencio, María A; Soto-Hernández, José Luís; Cárdenas, Graciela

2012-09-01

Highly active antiretroviral therapy (HAART) restores the inflammatory immune response in AIDS patients and it may unmask previous subclinical infections or paradoxically exacerbate symptoms of opportunistic infections. Up to 25% of patients receiving HAART develop immune reconstitution inflammatory syndrome (IRIS). We describe six patients with IRIS central nervous system (CNSIRIS) manifestations emphasizing the relevance of CSF cultures and neuroimaging in early diagnosis and management. Patients with CNSIRIS were identified among hospitalized HIV-infected patients that started HAART from January 2002 through December 2007 at a referral neurological center in Mexico. One-hundred and forty-two HIV-infected patients with neurological signs were hospitalized, 64 of which had received HAART, and six (9.3%) developed CNSIRIS. Five patients were male. Two cases of tuberculosis, two of cryptococcosis, one of brain toxoplasmosis, and one possible PML case were found. IRIS onset occurred within 12 weeks of HAART in five patients. Anti-infective therapy was continued. In one case, HAART was temporarily suspended. In long-term follow-up the clinical condition improved in all patients. CNSIRIS associated to opportunistic infections appeared in 9% of patients receiving HAART. Interestingly, no cases of malignancy or neoplasm IRIS-related were found. Frequent clinical assessment and neuroimaging studies supported diagnosis and treatment. Risk factors were similar to those found in other series. Copyright © 2012 Elsevier B.V. All rights reserved.

Strategies Utilized by Professional Nurses in the Primary Health ...

African Journals Online (AJOL)

Strategies Utilized by Professional Nurses in the Primary Health Care Facilities Regarding Adherence of Patients to Anti-Retroviral Therapy (ART) in Capricorn District, Limpopo Province, South Africa.

Adjuvant potential of virgin coconut oil extract on antiretroviral therapy-induced testicular toxicity: An ultrastructural study.

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Ogedengbe, O O; Jegede, A I; Onanuga, I O; Offor, U; Peter, A I; Akang, E N; Naidu, E C S; Azu, O O

2018-04-01

The effects of Virgin coconut oil as an adjuvant to highly active antiretroviral therapy (HAART) were investigated on the testicular ultrastructure and biochemical markers in rats. Twenty male Sprague-Dawley rats, weighing 153-169 g were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (HAART+Virgin coconut oil 10 ml/kg) and D (Virgin coconut oil [VCO] 10 ml/kg). Testicular segments were evaluated using transmission electron microscopy. Serum was assayed for testosterone, luteinising hormone, follicle stimulating hormone and testicular tissue for malondialdehyde and glutathione. Ultrastructure of basement membrane (Bm), mitochondria and spermatocytes was normal in the control group. HAART-treated group showed significant increase (p group. Mitochondrial cristae appear collapsed, and Sertoli cells showed cytoplasmic vacuolations. HAART+VCO group showed improved ultrastructural details in Bm, and Sertoli cell and Leydig cells show abundant lipid droplets. Virgin coconut oil-treated group showed thinning of Bm with otherwise normal ultrastructural features of organelles. HAART-treated group showed significant increase (p Virgin coconut oil improved testicular morphology and reversed HAART-induced ultrastructural alterations. Further studies on putative mechanism are required. © 2017 Blackwell Verlag GmbH.

Challenges in Initiating Antiretroviral Therapy in 2010

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Cécile L Tremblay

2010-01-01

Full Text Available Many clinical trials have shown that initiating antiretroviral therapy (ART at higher rather than lower CD4 T cell-positive counts results in survival benefit. Early treatment can help prevent end-organ damage associated with HIV replication and can decrease infectivity. The mainstay of treatment is either a non-nucleoside reverse transcriptase inhibitor or a ritonavir-boosted protease inhibitor in combination with two nucleoside reverse transcriptase inhibitors. While effective at combating HIV, ART can produce adverse alterations of lipid parameters, with some studies suggesting a relationship between some anti-retroviral agents and cardiovascular disease. As the HIV-positive population ages, issues such as hypertension and diabetes must be taken into account when initiating ART. Adhering to ART can be difficult; however, nonoptimal adherence to ART can result in the development of resistance; thus, drug characteristics and the patient’s preparedness to begin therapy must be considered. Reducing the pill burden through the use of fixed-dose antiretroviral drug combinations can facilitate adherence.

Adesão e não-adesão à terapia anti-retroviral: as duas faces de uma mesma vivência Adhesión y no adhesión a la terapia antiretroviral: las dos caras de una misma vivencia Adhesion and non adhesion to anti-retroviral therapy: the two faces of a same experience

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Ana Lúcia Cardoso Nogueira da Silva

2009-04-01

Full Text Available O objetivo do estudo foi compreender, a partir da perspectiva de portadores e familiares, os aspectos que influenciam na adesão à terapêutica anti-retroviral. Trata-se de um estudo descritivo, de natureza qualitativa, desenvolvido no período de junho de 2006 a julho de 2007, junto a 10 indivíduos portadores do HIV/Aids, acompanhados pelo Serviço de Atendimento Especializado em Aids de Campo Mourão - PR e seus familiares. Constituem fatores facilitadores da adesão: adoção de estratégias para lembrar horários e mascarar o gosto do medicamento, ausência de efeitos colaterais, número reduzido de medicamentos a serem ingeridos e capacidade para reconhecê-los, lembrança dos sintomas da doença e o apoio da rede social. A ausência destes fatores pode culminar na não-adesão.El objetivo del estudio fue comprender, a partir de la perspectiva de portadores y familiares, los aspectos que influyen en la adhesión a la terapéutica antiretroviral. Se trata de un estudio descriptivo, de naturaleza cualitativa, desarrollado en el período de junio de 2006 a julio de 2007, junto a 10 individuos portadores del VIH/SIDA, acompañados por el Servicio de Atención Especializado en SIDA de Campo Mourão - PR y sus familiares. Constituyen factores que facilitan la adhesión: adopción de estrategias para recordar horarios y enmascarar el sabor del medicamento, ausencia de efectos colaterales, número reducido de medicamentos a ser ingeridos y capacidad para reconocerlos, recuerdo de los síntomas de la enfermedad y el apoyo de la red social. La ausencia de estos factores puede culminar en la no-adhesión.The objective of the study was to understand, from the perspective of HIV bearers and family, the aspects that influence in the adhesion to the antiretroviral therapy. It is a descriptive study, of qualitative nature, carried out from June 2006 to July 2007, with 10 HIV/Aids positive individuals, attended at the Service of Specialized Care on Aids

Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation.

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Lapsia, Sameer; Koganti, Siva; Spadaro, Salvatore; Rajapakse, Ramona; Chawla, Anupama; Bhaduri-McIntosh, Sumita

2016-02-01

Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise. © 2015 Wiley Periodicals, Inc.

Hepatic histomorphological and biochemical changes following highly active antiretroviral therapy in an experimental animal model: Does Hypoxis hemerocallidea exacerbate hepatic injury?

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Onyemaechi Okpara Azu

Full Text Available As the roll-out of antiretroviral therapy continues to drive downwards morbidity and mortality in people living with HIV/AIDS (PLWHAs, organ toxicities (especially the liver are frequently becoming a major concern for researchers, scientists and healthcare planners.This study was conducted to investigate the possible protective effect of Hypoxis hemerocallidea (AP against highly active antiretroviral therapy (HAART-induced hepatotoxicity. A total of 63 pathogen-free adult male Sprague-Dawley rats were divided into 9 groups and treated according to protocols.While no mortality was reported, animals treated with adjuvant HAART and AP recorded least% body weight gain. Significant derangements in serum lipid profiles were exacerbated by treatment of with AP as LDL (increased p < 0.03, triglycerides (increased p < 0.03 with no change in total cholesterol levels. Adjuvant AP with HAART caused reduction in LDL (p < 0.05 and 0.03, increased HDL (p < 0.05 and TG (p < 0.05 and 0.001 for AP100 and AP200 doses respectively. Markers of liver injury assayed showed significant increase (p < 0.003, 0.001 in AST in AP alone as well as HAART+ vitamins C and E groups respectively. Adjuvant HAART and AP and vitamins C and E also caused significant declines in ALT and ALP levels. Serum GGT was not markedly altered. Disturbances in histopathology ranged from severe hepatocellular distortions, necrosis and massive fibrosis following co-treatment of HAART with vitamins C and E as well as HAART alone. These results warrant caution on the adjuvant use of AP with HAART by PLWHAs as implications for hepatocellular injuries are suspect with untoward cardiometabolic changes. Keywords: Liver morphology, HAART, Cytotoxicity, Stains, Biochemistry, Lipid profile

Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

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Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

2016-05-26

The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

Breast cancer and HIV in the era of highly active antiretroviral therapy: two case reports and review of the literature.

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Latif, Naeem; Rana, Fauzia; Guthrie, Troy

2011-01-01

The incidence of human immunodeficiency virus (HIV) infection is rising in US women; however its impact on breast cancer incidence, stage at presentation, response and treatment toxicity remains unknown. To address the impact of HIV infection and use of highly active antiretroviral therapy (HAART) on the natural history of breast cancer we present two cases of breast cancer in HIV-infected women and also review the literature. A literature search was done on Medline using the key words HIV/AIDS, breast cancer, and HAART therapy, restricted to English language. There were mostly case reports and one large series of 20 cases reported by Hurley et al. Data concerning the impact of HIV infection and HAART therapy regarding pathogenesis, stage at presentation, tumor type, response, and toxicity associated with treatment were reviewed. The literature review shows that the breast cancer incidence is either same or less in HIV-infected patients compared to the general population. However, the patients with HIV infection present with more advanced stage and aggressive disease, and they also have poor chemotherapy tolerance. The impact of HAART on breast cancer incidence in HIV-infected patients is still unclear. © 2010 Wiley Periodicals, Inc.

Bidirectional Retroviral Integration Site PCR Methodology and Quantitative Data Analysis Workflow.

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Suryawanshi, Gajendra W; Xu, Song; Xie, Yiming; Chou, Tom; Kim, Namshin; Chen, Irvin S Y; Kim, Sanggu

2017-06-14

Integration Site (IS) assays are a critical component of the study of retroviral integration sites and their biological significance. In recent retroviral gene therapy studies, IS assays, in combination with next-generation sequencing, have been used as a cell-tracking tool to characterize clonal stem cell populations sharing the same IS. For the accurate comparison of repopulating stem cell clones within and across different samples, the detection sensitivity, data reproducibility, and high-throughput capacity of the assay are among the most important assay qualities. This work provides a detailed protocol and data analysis workflow for bidirectional IS analysis. The bidirectional assay can simultaneously sequence both upstream and downstream vector-host junctions. Compared to conventional unidirectional IS sequencing approaches, the bidirectional approach significantly improves IS detection rates and the characterization of integration events at both ends of the target DNA. The data analysis pipeline described here accurately identifies and enumerates identical IS sequences through multiple steps of comparison that map IS sequences onto the reference genome and determine sequencing errors. Using an optimized assay procedure, we have recently published the detailed repopulation patterns of thousands of Hematopoietic Stem Cell (HSC) clones following transplant in rhesus macaques, demonstrating for the first time the precise time point of HSC repopulation and the functional heterogeneity of HSCs in the primate system. The following protocol describes the step-by-step experimental procedure and data analysis workflow that accurately identifies and quantifies identical IS sequences.

Metabolic Syndromes Associated with HIV: Mitigating the Side Effects of Drug Therapy.

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Stringer, William W.; Sattler, Fred R.

2001-01-01

HIV infection and highly active antiretroviral therapy (HAART) are associated with such metabolic disorders as AIDS wasting syndrome, metabolic dysregulation, and abnormalities of serum lipids. Adjunctive therapies (e.g., diet and antilipid therapy); risk factor modification (e.g., smoking cessation and blood pressure control); aerobic exercise;…

Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients

DEFF Research Database (Denmark)

Lødrup, A; Pottegård, A; Hallas, J

2015-01-01

BACKGROUND: Guidelines recommend that patients with gastro-oesophageal reflux disease are adequately treated with acid-suppressive therapy before undergoing anti-reflux surgery. Little is known of the use of acid-suppressive drugs before anti-reflux surgery. AIM: To determine the use of proton pump...... inhibitors and H2 -receptor antagonists in the year before anti-reflux surgery. METHODS: A nationwide retrospective study of all patients aged ≥18 undergoing first-time anti-reflux surgery in Denmark during 2000-2012 using data from three different sources: the Danish National Register of Patients......, the Danish National Prescription Register, and the Danish Person Register. RESULTS: The study population thus included 2922 patients (median age: 48 years, 55.7% male). The annual proportion of patients redeeming ≥180 DDD of acid-suppressive therapy increased from 17.0% 5 years before anti-reflux surgery...

Detection of a human intracisternal A-type retroviral particle antigenically related to HIV

Science.gov (United States)

Garry, R. F.; Fermin, C. D.; Hart, D. J.; Alexander, S. S.; Donehower, L. A.; Luo-Zhang, H.

1990-01-01

Sjogren's syndrome is an autoimmune disease that is characterized by dryness of the mouth and eyes. The loss of salivary and lacrimal gland function is accompanied by lymphocytic infiltration. Because similar symptoms and glandular pathology are observed in certain persons infected with human immunodeficiency virus (HIV), a search was initiated for a possible retroviral etiology in this syndrome. A human intracisternal A-type retroviral particle that is antigenically related to HIV was detected in lymphoblastoid cells exposed to homogenates of salivary tissue from patients with Sjogren's syndrome. Comparison of this retroviral particle to HIV indicates that they are distinguishable by several ultrastructural, physical, and enzymatic criteria.

Impact of highly active antiretroviral therapy in the development and remission of oral plasmablastic lymphoma

Directory of Open Access Journals (Sweden)

Vivian Petersen Wagner

2016-01-01

Full Text Available Plasmablastic lymphoma (PBL represents a rare type of non-Hodgkin lymphoma associated with human immunodeficiency virus (HIV infection. The impact of highly active antiretroviral therapy (HAART in this tumor is poorly known due to its small incidence. This study reports a case of a 33-year-old HIV-positive woman who was referred to the Stomatology Department complaining about a painful gingival growth and cervical nodule both with 20 days of evolution. The lesions appeared 7 months after the patient stopped HAART. The final diagnosis was PBL. After resuming HAART for 45 days, the gingival lesion presented complete remission. The patient continued with HAART alongside chemotherapy. At 24 months follow-up, the patient was stable. The dental surgeon plays an essential role in orientation and retention in care of HIV patients once the adherence of HAART seems to play an important role in PBL development and response to treatment.

Functional cloning using pFB retroviral cDNA expression libraries.

Science.gov (United States)

Felts, Katherine A; Chen, Keith; Zaharee, Kim; Sundar, Latha; Limjoco, Jamie; Miller, Anna; Vaillancourt, Peter

2002-09-01

Retroviral cDNA expression libraries allow the efficient introduction of complex cDNA libraries into virtually any mitotic cell type for screening based on gene function. The cDNA copy number per cell can be easily controlled by adjusting the multiplicity of infection, thus cell populations may be generated in which >90% of infected cells contain one to three cDNAs. We describe the isolation of two known oncogenes and one cell-surface receptor from a human Burkitt's lymphoma (Daudi) cDNA library inserted into the high-titer retroviral vector pFB.

Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption

DEFF Research Database (Denmark)

Dore, Gregory J; Soriano, Vicente; Rockstroh, Jürgen

2010-01-01

.0002), nondetectable HBV DNA at baseline (P = 0.007), and black race (P = 0.03). Time to ART reinitiation was shorter (7.5, 15.6, and 17.8 months; P hepatitis C virus-positive and non-HBV/hepatitis...... C virus participants in the drug conservation arm. No hepatic decompensation events occurred among HBV-positive participants in either arm. CONCLUSION: HBV DNA rebound following ART interruption is common and may be associated with accelerated immune deficiency in HIV-HBV-coinfected patients.......BACKGROUND: The impact of antiretroviral therapy (ART) interruption in HIV-hepatitis B virus (HBV)-coinfected patients was examined in the Strategic Management of AntiRetroviral Therapy (SMART) study. METHODS: Plasma HBV DNA was measured in all hepatitis B surface antigen-positive (HBV...

Viral persistence, latent reservoir, and blips: a review on HIV-1 dynamics and modeling during HAART and related treatment implications

Energy Technology Data Exchange (ETDEWEB)

Rong, Libin [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

2008-01-01

HIV-1 eradication from infected individuals has not been achieved with the use of highly active antiretroviral therapy (HAART) for a prolonged period of time. The cellular reservoir for HIV-1 in resting memory CD4{sup +} T cells remains a major obstacle to viral elimination. The reservoir does not decay significantly over long periods of time as is able to release replication competent HIV-1 upon cell activation. Residual ongoing viral replication may likely occur in many patients because low levels of virus can be detected in plasma by sensitive assays and transient episodes of viremia, or HIV-1 blips, are often observed in patients even with successful viral suppression for many years. Here we review our current knowledge of the factors contributing to viral persistence, the latent reservoir, and blips, and mathematical models developed to explore them and their relationships. We show how mathematical modeling can help improve our understanding of HIV-1 dynamics in patients on HAART and the quantitative events underlying HIV-1 latency, reservoir stability, low-level viremic persistence, and emergence of intermittent viral blips. We also discuss treatment implications related to these studies.

Mapping chemical structure-activity information of HAART-drug cocktails over complex networks of AIDS epidemiology and socioeconomic data of U.S. counties.

Science.gov (United States)

Herrera-Ibatá, Diana María; Pazos, Alejandro; Orbegozo-Medina, Ricardo Alfredo; Romero-Durán, Francisco Javier; González-Díaz, Humberto

2015-06-01

Using computational algorithms to design tailored drug cocktails for highly active antiretroviral therapy (HAART) on specific populations is a goal of major importance for both pharmaceutical industry and public health policy institutions. New combinations of compounds need to be predicted in order to design HAART cocktails. On the one hand, there are the biomolecular factors related to the drugs in the cocktail (experimental measure, chemical structure, drug target, assay organisms, etc.); on the other hand, there are the socioeconomic factors of the specific population (income inequalities, employment levels, fiscal pressure, education, migration, population structure, etc.) to study the relationship between the socioeconomic status and the disease. In this context, machine learning algorithms, able to seek models for problems with multi-source data, have to be used. In this work, the first artificial neural network (ANN) model is proposed for the prediction of HAART cocktails, to halt AIDS on epidemic networks of U.S. counties using information indices that codify both biomolecular and several socioeconomic factors. The data was obtained from at least three major sources. The first dataset included assays of anti-HIV chemical compounds released to ChEMBL. The second dataset is the AIDSVu database of Emory University. AIDSVu compiled AIDS prevalence for >2300 U.S. counties. The third data set included socioeconomic data from the U.S. Census Bureau. Three scales or levels were employed to group the counties according to the location or population structure codes: state, rural urban continuum code (RUCC) and urban influence code (UIC). An analysis of >130,000 pairs (network links) was performed, corresponding to AIDS prevalence in 2310 counties in U.S. vs. drug cocktails made up of combinations of ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4856 protocols, and 10 possible experimental measures. The best model found with the original

Anti-B cell antibody therapies for inflammatory rheumatic diseases

DEFF Research Database (Denmark)

Faurschou, Mikkel; Jayne, David R W

2014-01-01

Several monoclonal antibodies targeting B cells have been tested as therapeutics for inflammatory rheumatic diseases. We review important observations from randomized clinical trials regarding the efficacy and safety of anti-B cell antibody-based therapies for rheumatoid arthritis, systemic lupus...... and functions in rheumatic disorders. Future studies should also evaluate how to maintain disease control by means of conventional and/or biologic immunosuppressants after remission-induction with anti-B cell antibodies....

Cost-Effectiveness of Highly Active Antiretroviral Therapy in South Africa.

Directory of Open Access Journals (Sweden)

2005-12-01

Full Text Available BACKGROUND: Little information exists on the impact of highly active antiretroviral therapy (HAART on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices. METHODS AND FINDINGS: Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3 and 27 with AIDS (WHO stage 4 receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group. Costs of service provision (January 2004 prices, US$1 = 7.6 Rand included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY, whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97-1.19 for the HAART group versus 3.73 (95% CI: 3.55-3.97 for the No-ART group, and 8.71 (95% CI: 8.40-9.03 versus 4.35 (95% CI: 4.12-5.61, respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63-2.52 for the HAART versus 15.36 (95% CI: 13.97-16.85 for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81-8.49 compared with 6.60 (95% CI: 5.69-7.62 respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964

Cost-effectiveness of highly active antiretroviral therapy in South Africa.

Directory of Open Access Journals (Sweden)

Motasim Badri

2006-01-01

Full Text Available Little information exists on the impact of highly active antiretroviral therapy (HAART on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices.Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3 and 27 with AIDS (WHO stage 4 receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group. Costs of service provision (January 2004 prices, USD 1 = 7.6 Rand included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY, whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97-1.19 for the HAART group versus 3.73 (95% CI: 3.55-3.97 for the No-ART group, and 8.71 (95% CI: 8.40-9.03 versus 4.35 (95% CI: 4.12-5.61, respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63-2.52 for the HAART versus 15.36 (95% CI: 13.97-16.85 for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81-8.49 compared with 6.60 (95% CI: 5.69-7.62 respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964 for the HAART group for scenario 1

Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone

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Carl K Edwards

2012-12-01

Full Text Available Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs or anti-TNF-α therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable" RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a DMARD and an anti-TNF-α agent (infliximab or etanercept to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N=122, unstable DMARD patients (N=18, stable DMARD patients (N=26, and stable patients on combination therapy (N=20. Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNF-α therapy. Furthermore, combination DMARD and anti-TNF-α therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

Rapid resolution of cellulitis in patients managed with combination antibiotic and anti-inflammatory therapy.

Science.gov (United States)

Dall, Lawrence; Peterson, Sandford; Simmons, Tom; Dall, Amy

2005-03-01

There is some evidence to suggest that host inflammatory response has some effect on the clinical manifestations of cellulitis. The objective of this pilot study was to investigate whether the addition of oral nonsteroidal anti-inflammatory (NSAI) therapy to antibiotic treatment hastens resolution of cellulitis-related inflammation. Patients presenting in the emergency department with signs and symptoms of class II cellulitis were assigned to receive treatment with either antibiotic therapy alone (intravenous, supplemented with oral cephalexin or an equivalent) for 10 days (n = 33) or antibiotic therapy for 10 days plus an oral anti-inflammatory (ibuprofen 400 mg every 6 hours) for 5 days (n = 31). Patients were discharged as soon as possible to complete their therapy on an outpatient basis. The addition of an oral anti-inflammatory agent significantly (P < .05) shortened the time to regression of inflammation and complete resolution of cellulitis. Twenty-four of 29 evaluable patients (82.8%) who received supplemental anti-inflammatory treatment showed regression of inflammation within 1 to 2 days compared with only 3 of 33 patients (9.1%) treated without an anti-inflammatory in the same time frame. All patients receiving adjunctive anti-inflammatory treatment experienced complete resolution of cellulitis in 4 to 5 days or less, while 24.2% (8/33) of patients treated with antibiotic alone required 6 to 7 days, and 6.1% (2/33) required 7 days or more (P < .05). This small preliminary study provides some promising data, suggesting that the supplemental use of anti-inflammatory therapy may hasten the time to regression of inflammation and complete resolution of cellulitis.

Monitoring of anti-cancer therapies and chemoresistance

Czech Academy of Sciences Publication Activity Database

Martinková, Jiřina; Hrabáková, Rita; Skalníková, Helena; Novák, Petr; Džubák, P.; Hajdúch, M.; Gadher, S. J.; Kovářová, Hana

2009-01-01

Roč. 6, č. 1 (2009), s. 63-63 ISSN 1109-6535. [International Conference of the Hellenic Proteomic Society /3./. 30.03.2009-01.04.2009, Nafplio] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : anti-cancer therapies Subject RIV: CE - Biochemistry

Antiretroviral therapy initiation before, during, or after pregnancy in HIV-1-infected women: maternal virologic, immunologic, and clinical response.

Directory of Open Access Journals (Sweden)

Vlada V Melekhin

2009-09-01

Full Text Available Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.We conducted a retrospective cohort study from 1997-2005 among 112 pregnant HIV-infected women who started HAART before (N = 12, during (N = 70 or after pregnancy (N = 30.Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (-0.35 vs. 0.10 log(10 copies/mL, P = 0.03 and 183.8 vs. -70.8 cells/mm(3, P = 0.03, respectively but similar to those initiating HAART before pregnancy (-0.32 log(10 copies/mL, P = 0.96 and 155.8 cells/mm(3, P = 0.81, respectively. There were 3 (25% AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4% in those initiating HAART during pregnancy, and 5 (17% in those initiating after pregnancy (P = 0.01. There were no statistical differences in rates of HIV disease progression between groups.HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

Anti-leukemic therapies induce cytogenetic changes of human bone marrow-derived mesenchymal stem cells.

Science.gov (United States)

Yeh, Su-Peng; Lo, Wen-Jyi; Lin, Chiao-Lin; Liao, Yu-Min; Lin, Chen-Yuan; Bai, Li-Yuan; Liang, Ji-An; Chiu, Chang-Fang

2012-02-01

Both bone marrow hematopoietic cells (BM-HCs) and mesenchymal stem cells (BM-MSCs) may have cytogenetic aberrations in leukemic patients, and anti-leukemic therapy may induce cytogenetic remission of BM-HCs. The impact of anti-leukemic therapy on BM-MSCs remains unknown. Cytogenetic studies of BM-MSCs from 15 leukemic patients with documented cytogenetic abnormalities of BM-HCs were investigated. To see the influence of anti-leukemic therapy on BM-MSCs, cytogenetic studies were carried out in seven of them after the completion of anti-leukemic therapy, including anthracycline/Ara-C-based chemotherapy in two patients, high-dose busulfan/cyclophosphamide-based allogeneic transplantation in two patients, and total body irradiation (TBI)-based allogeneic transplantation in three patients. To simulate the effect of TBI in vitro, three BM-MSCs from one leukemic patient and two normal adults were irradiated using the same dosage and dosing schedule of TBI and cytogenetics were re-examined after irradiation. At the diagnosis of leukemia, two BM-MSCs had cytogenetic aberration, which were completely different to their BM-HCs counterpart. After the completion of anti-leukemic therapy, cytogenetic aberration was no longer detectable in one patient. Unexpectedly, BM-MSCs from three patients receiving TBI-based allogeneic transplantation acquired new, clonal cytogenetic abnormalities after transplantation. Similarly, complex cytogenetic abnormalities were found in all the three BM-MSCs exposed to in vitro irradiation. In conclusion, anti-leukemic treatments induce not only "cytogenetic remission" but also new cytogenetic abnormalities of BM-MSCs. TBI especially exerts detrimental effect on the chromosomal integrity of BM-MSCs and highlights the equal importance of investigating long-term adverse effect of anti-leukemic therapy on BM-MSCs as opposed to beneficial effect on BM-HCs.

Antiretroviral therapy (ART) rationing and access mechanisms and their impact on youth ART utilization in Malawi.

Science.gov (United States)

Dixon, Jimmy-Gama; Gibson, Sarah; McPake, Barbara; Maleta, Ken

2011-06-01

The World Health Organization (WHO) staging is a commonly used rationing mechanism for highly active antiretroviral therapy (HAART) among various HIV infected populations including youths in most developing countries. Rationing is defined as any policy or practice that restricts consumption of or access to certain goods due to its limited supply. However, as HIV prevalence is rapidly increasing among youth, understanding the capacity of the staging approach to achieve HAART uptake in youth is of considerable importance. This study aimed to explore how HAART rationing and access mechanisms impact on youth's utilization of HAART in Malawi. The study used mixed methods with quantitative analysis of existing Ministry of Health Clinical HIV Unit data used to determine existing levels of youth HAART use. Qualitative methods employed in-depth interviews that interviewed nine ART providers, nine HIV positive youth on HAART and nine HIV positive youth not on HAART; and field observations to nine ART clinics were used to understand HAART rationing and access mechanisms and how such mechanisms impact youth uptake of HAART. The findings revealed that ART providers use both explicit rationing mechanisms like WHO clinical staging and implicit rationing mechanisms like use of waiting lists, queues and referral in ART provision. However, the WHO staging approach had some challenges in its implementation. It was also observed that factors like non-comprehensive approach to HAART provision, costs incurred to access HAART, negative beliefs and misconceptions about HAART and HIV were among the key factors that limit youth access to HAART. The study recommends that while WHO staging is successful as a rationing mechanism in Malawi, measures should be put in place to improve access to CD4 assessment for clients who may need it. ART providers also need to be made aware of the implicit rationing mechanisms that may affect HAART access. There is also need to improve monitoring of those HIV

Anti-TNF-alpha therapy for sight threatening uveitis.

NARCIS (Netherlands)

E.W. Lindstedt (Eric); G.S. Baarsma (Seerp); R.W.A.M. Kuijpers (Robert); P.M. van Hagen (Martin)

2005-01-01

textabstractAIM: To describe the effect of additional treatment with anti-TNF-alpha therapy in a case series of 13 patients with serious sight threatening uveitis. METHODS: 13 patients with serious sight threatening uveitis were included, of whom six had Behcet's disease, five had idiopathic

A short history of anti-rheumatic therapy. II. Aspirin

Directory of Open Access Journals (Sweden)

P. Marson

2011-06-01

Full Text Available The discovery of aspirin, an antipyretic, anti-inflammatory and analgesic drug, undoubtedly represents a milestone in the history of medical therapy. Since ancient times the derivatives of willow (Salix alba were used to treat a variety of fevers and pain syndromes, although the first report dates back to 1763 when the English Reverend Edward Stone described the effect of an extract of the bark willow in treating malaria. In the XIX century many apothecaries and chemists, including the Italian Raffaele Piria and Cesare Bertagnini, developed the biological processes of extraction and chemical synthesis of salicylates, and then analyzed their therapeutic properties and pharmacokinetic and pharmacodynamic characteristics. In 1899 the Bayer Company, where Felix Hoffmann, Heinrich Dreser and Arthur Eichengrün worked, recorded acetyl-salicylic acid under the name “Aspirin”. In the XX century, besides the definition of the correct applications of aspirin in the anti-rheumatic therapy being defined, Lawrence L. Crawen identified the property of this drug as an anti-platelet agent, thus opening the way for more widespread uses in cardiovascular diseases.

Chromosomal locations of members of a family of novel endogenous human retroviral genomes

International Nuclear Information System (INIS)

Horn, T.M.; Huebner, K.; Croce, C.; Callahan, R.

1986-01-01

Human cellular DNA contains two distinguishable families of retroviral related sequences. One family shares extensive nucleotide sequence homology with infectious mammalian type C retroviral genomes. The other family contains major regions of homology with the pol genes of infectious type A and B and avian type C and D retroviral genomes. Analysis of the human recombinant clone HLM-2 has shown that the pol gene in the latter family is located within an endogenous proviral genome. The authors show that the proviral genome in HLM-2 and the related recombinant clone HLM-25 are located, respectively, on human chromosomes 1 and 5. Other related proviral genomes are located on chromosomes 7, 8, 11, 14, and 17

Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: successful management with intravitreal injections and monitoring with quantitative PCR.

Science.gov (United States)

Yin, Philip D; Kurup, Shree K; Fischer, Steven H; Rhee, Henry H; Byrnes, Gordon A; Levy-Clarke, Grace A; Buggage, Ronald R; Nussenblatt, Robert B; Mican, JoAnn M; Wright, Mary E

2007-03-01

Progressive outer retinal necrosis (PORN) is an ocular disease in individuals with AIDS and is associated with substantial morbidity. The optimal management of PORN and its clinical course in the HAART era is unclear. We report a case of successfully managed PORN that provides insight into the monitoring and treatment of this disease. Intravitreal injections and intravenous therapy targeted towards varicella zoster virus (VZV) were used to treat PORN. HAART was initiated for HIV-1 therapy. Serial PCR for VZV was performed on aqueous humor to monitor the clinical course. The presence of VZV DNA from aqueous humor correlated with clinical exacerbations of disease. Initiation of twice weekly intravitreal injections with dual antiviral drugs appeared to be an important therapeutic intervention that resulted in remission of PORN. Secondary prophylaxis against VZV was successfully withdrawn after HAART induced partial immune recovery. In addition to aggressive therapy with intravitreal injections, HAART and quantitative measurements of VZV DNA from aqueous humor have important roles in the management of PORN. A multidisciplinary approach involving specialists in infectious diseases, ophthalmology, and clinical microbiology will improve the chances for successful long-term outcomes.

Effective CD4+ T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses.

Science.gov (United States)

Macal, M; Sankaran, S; Chun, T-W; Reay, E; Flamm, J; Prindiville, T J; Dandekar, S

2008-11-01

Human immunodeficiency virus (HIV) infection leads to severe CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) that persists despite the initiation of highly active antiretroviral therapy (HAART). It is not known whether restoration of gut mucosal CD4+ T cells and their functions is feasible during therapy and how that relates to immune correlates and viral reservoirs. Intestinal biopsies and peripheral blood samples from HIV-infected patients who were either HAART naive or on long-term HAART were evaluated. Our data demonstrated that gut CD4+ T-cell restoration ranged from modest (50%), compared with uninfected controls. Despite persistent CD4+ T-cell proviral burden and residual immune activation in GALT during HAART, effective CD4+ T-cell restoration (>50%) was achieved, which was associated with enhanced Th17 CD4+ T-cell accumulation and polyfunctional anti-HIV cellular responses. Our findings suggest that a threshold of>50% CD4+ T-cell restoration may be sufficient for polyfunctional HIV-specific T cells with implications in the evaluation of vaccines and therapeutics.

Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.

Science.gov (United States)

Kumar, Santosh; Rao, P S S; Earla, Ravindra; Kumar, Anil

2015-03-01

Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse.

[Disorders of lipid and glucose metabolism. Long-term adverse effects of antiretroviral therapy].

Science.gov (United States)

Landauer, N; Goebel, F D

2002-04-09

In addition to readily controllable short-term side effects, highly active antiretroviral therapy (HAART) also has long-term side effects: lipodystrophy syndrome, hyperlipoproteinemia, insulin resistance, elevated glucose tolerance sometimes leading to diabetes mellitus and lactic acidosis. The pathogenesis remains uncertain although various hypotheses have been advanced. A number of approaches for the treatment of lipodystrophy are available, the effects of which, however, have not been confirmed by study results. Hyperlipoproteinemia probably means an increased cardiovascular risk, but a final pronouncement on this is not yet possible. Fibrates and statins are currently applied for treatment, but interactions with HAART medicaments have to be considered. HAART-induced diabetes mellitus presents clinically as type 2 diabetes, and is treated accordingly.

Issues in cervical cancer incidence and treatment in HIV.

Science.gov (United States)

Einstein, Mark H; Phaëton, Rébécca

2010-09-01

Cervical disease burden continues to be especially high in HIV-infected women, even in the era of effective antiretroviral medications. This review discusses the multiple issues surrounding HIV-associated cervical cancer. Also, the unique treatment-related issues in HIV-associated cervical cancer are addressed. The incidence of invasive cervical cancer has remained stable in industrialized nations; however, it is only estimated in developing countries secondary to a relative lack of data collection and registries. Trends in HIV-associated cervical cancer have changed in the highly active antiretroviral therapy (HAART) era. Recent molecular pathways suggest that the natural progression of human papillomavirus infection, the causal agent in all cervical cancers, may be related to immune system dysfunction as well as HIV/human papillomavirus synergistic mechanisms. When highly active retroviral therapies are used, invasive cervical cancer treatments are impacted by concomitant drug toxicities that could potentially limit therapeutic benefit of either HAART or the standard of care treatment for locally advanced cervical cancer, concomitant chemoradiotherapy. The significance and care of the patient with invasive cervical cancer is becoming a geographically relevant phenomenon such that it may be time to re-address the global definition. Further studies in treatment issues and drug-drug interactions with cervical cancer treatments in the setting of HIV are paramount.

Patients' perceptions of a rural decentralised anti-retroviral therapy ...

African Journals Online (AJOL)

2017-09-03

Sep 3, 2017 ... management and its impact on direct out-of-pocket spending. Monique Lines1, Fatima Suleman2. 1. Postgraduate Student, Discipline of Pharmaceutical Sciences, School of Health ..... collecting pension money every month.

[Effect of anti-inflammatory therapy on the treatment of dry eye syndrome].

Science.gov (United States)

Mrukwa-Kominek, Ewa; Rogowska-Godela, Anna; Gierek-Ciaciura, Stanisława

2007-01-01

Dry eye syndrome is a common chronic disease; agents and strategies for its effective management are still lacking. The syndrome tends to be accompanied by ocular surface inflammation; therefore, the use of anti-inflammatory agents might prove beneficial. The authors present up-to-date guidelines, strategies, and efficacy of dry eye syndrome management, including anti-inflammatory treatment. As no diagnostic tests are now available to assess ocular surface inflammation severity, the right timing to launch an anti-inflammatory agent is difficult to determine. Patients with mild intermittent bouts of symptoms which can be alleviated with ophthalmic lubricants do not typically require anti-inflammatory therapy. The latter should be considered in those who do not respond to lubricating drops, obtain poor results on clinical tests, and show symptoms of ocular surface irritation (eg. conjunctivae redness). Anti-inflammatory treatment of dry eye syndrome may include short-term corticosteroids, cyclosporine A emulsion, oral tetracycline therapy, oral omega-3 fatty acid supplements, and autologous serum eye drops. Anti-inflammatory treatment should be safe and effective; potential benefits should be evaluated for each individual patient. The authors have reviewed the advantages of anti-inflammatory treatment in dry eye syndrome, presented in literature.

Clinical outcome of HIV-infected patients with sustained virologic response to antiretroviral therapy: long-term follow-up of a multicenter cohort.

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Félix Gutierrez

Full Text Available BACKGROUND: Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. METHODS: Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. RESULTS: Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9% patients died (mortality rate 0.86 per 100 person-years, and 40 (5.3% died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68-10.83]; P = .002, and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02-1.09; P = .001. Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. CONCLUSIONS: Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected.

Anti-TNFα therapy for chronic inflammatory disease in kidney transplant recipients: Clinical outcomes.

Science.gov (United States)

Garrouste, Cyril; Anglicheau, Dany; Kamar, Nassim; Bachelier, Claire; Rivalan, Joseph; Pereira, Bruno; Caillard, Sophie; Aniort, Julien; Gatault, Philippe; Soubrier, Martin; Sayegh, Johnny; Colosio, Charlotte; Buisson, Anthony; Thervet, Eric; Bouvier, Nicolas; Heng, Anne Elisabeth

2016-10-01

Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34-51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1).Anti-TNFα therapies resulted in a clinical response in 13/16 patients (81%). Estimated glomerular filtration rates (MDRD-4) were similar on day 0 and at 24 months (M24) after anti-TNFα treatment had been initiated (41 [12-55] and 40 [21-53] mL/min/1.73 m, respectively). Two allograft losses were observed. The 1st case was due to antibody-mediated rejection (M18), while the 2nd was the result of AA amyloidosis recurrence (M20). There were several complications: 8 patients (50%) developed 23 serious infections (18 bacterial, 4 viral, and 1 fungal) and 4 developed cancer. Five patients died (infection n = 2, cardiac AA amyloidosis n = 1, intraalveolar hemorrhage following microscopic polyangiitis n = 1, and acute respiratory distress syndrome n = 1). On univariate analysis, recipient age associated with death (P = 0.009) and infection development (P = 0.06).Using anti-TNFα therapies, remission can be achieved in chronic inflammatory diseases in kidney-transplant patients. However, concommitant anti-TNFα and immunosuppresive therapies must be used with caution due to the high risk of infection, particularly after the age of 50.

Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies

DEFF Research Database (Denmark)

May, M; Sterne, JAC; Sabin, C

2007-01-01

of AIDS or death (death alone) from the start of HAART ranged from 5.6 to 77% (1.8-65%), depending on age, CD4 cell count, HIV-1-RNA level, clinical stage, and history of injection drug use. From 6 months the corresponding figures were 4.1-99% for AIDS or death and 1.3-96% for death alone. CONCLUSION......: On the basis of data collected routinely in HIV care, prognostic models with high discriminatory power over 5 years were developed for patients starting HAART in industrialized countries. A risk calculator that produces estimates for progression rates at years 1 to 5 after starting HAART is available from www.art-cohort-collaboration.org....

Highly active antiretroviral therapy adherence and its determinants in selected regions in Indonesia

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Felix F. Widjaja

2011-02-01

Full Text Available Background: Highly active antiretroviral therapy (HAART can reduce morbidity and mortality of HIV-infected patients. However, it depends upon adherence to medication. The objective of this study was to examine the adherence to HAART and to evaluate individual patient characteristics i.e. self-efficacy, depression level, and social support and to finally determine HAART adherence in selected regions in Indonesia.Methods: This cross-sectional study was conducted in Jakarta, Malang, Bandung, Makasar and Banda Aceh. The subject of the study was HIV-infected patients who were older than 13 years old and had taken HAART for at least a month. They were recruited consecutively then asked how many pills they had missed during the previous month. Poor adherence can be stated if the percentage of adherence rate is below 95%. HIV treatment adherence self-efficacy scale  (HIVASES, Beck Depression Inventory (BDI-II and Interpersonal Support Evaluation List (ISEL was adapted to assess self-efficacy, depression level and social support, respectively.Results: We found that 96% (n=53 of the subjects adhered to HAART. There were no associations between adherence with self-efficacy, depression level, and social support. The main cause of non-adherence in this study was ‘simply  forget’.Conclusion: Adherence to HAART was found to be high and not associated with self-efficacy, depression level and social support in some central regions in Indonesia. (Med J Indones 2011; 20:50-5Keywords: adherence, depression, HAART, HIV, self-efficacy, social support

Retroviral-mediated gene transfer of human phenylalanine hydroxylase into NIH 3T3 and hepatoma cells

Energy Technology Data Exchange (ETDEWEB)

Ledley, F.D.; Grenett, H.E.; McGinnis-Shelnutt, M.; Woo, S.L.C.

1986-01-01

Phenylketonuria (PKU) is caused by deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). A full-length human PAH cDNA sequence has been inserted into pzip-neoSV(X), which is a retroviral vector containing the bacterial neo gene. The recombinant has been transfected into Psi2 cells, which provide synthesis of the retroviral capsid. Recombinant virus was detected in the culture medium of the transfected Psi2 cells, which is capable of transmitting the human PAH gene into mouse NIH 3T3 cells by infection leading to stable incorporation of the recombinant provirus. Infected cells express PAH mRNA, immunoreactive PAH protein, and exhibit pterin-dependent phenylaline hydroxylase activity. The recombinant virus is also capable of infecting a mouse hepatoma cell line that does not normal synthesize PAH. PAH activity is present in the cellular extracts and the entire hydroxylation system is reconstituted in the hepatoma cells infected with the recombinant viruses. Thus, recombinant viruses containing human PAH cDNA provide a means for introducing functional PAH into mammalian cells of hepatic origin and can potentially be introduced into whole animals as a model for somatic gene therapy for PKU.

Hypercholesterolemia is associated with the apolipoprotein C-III (APOC3 genotype in children receiving HAART: an eight-year retrospective study.

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Carlos A Rocco

Full Text Available Polymorphisms in apolipoprotein genes have shown to be predictors of plasma lipid levels in adult cohorts receiving highly active antiretroviral therapy (HAART. Our objective was to confirm the association between the APOC3 genotype and plasma lipid levels in an HIV-1-infected pediatric cohort exposed to HAART. A total of 130 HIV-1-infected children/adolescents that attended a reference center in Argentina were selected for an 8-year longitudinal study with retrospective data collection. Longitudinal measurements of plasma triglycerides, total cholesterol, HDL-C and LDL-C were analyzed under linear or generalized linear mixed models. The contribution of the APOC3 genotype at sites -482, -455 and 3238 to plasma lipid levels prediction was tested after adjusting for potential confounders. Four major APOC3 haplotypes were observed for sites -482/-455/3238, with estimated frequencies of 0.60 (C/T/C, 0.14 (T/C/C, 0.11 (C/C/C, and 0.11 (T/C/G. The APOC3 genotype showed a significant effect only for the prediction of total cholesterol levels (p<0.0001. However, the magnitude of the differences observed was dependent on the drug combination (p = 0.0007 and the drug exposure duration at the time of the plasma lipid measurement (p = 0.0002. A lower risk of hypercholesterolemia was predicted for double and triple heterozygous individuals, mainly at the first few months after the initiation of Ritonavir-boosted protease inhibitor-based regimens. We report for the first time a significant contribution of the genotype to total cholesterol levels in a pediatric cohort under HAART. The genetic determination of APOC3 might have an impact on a large portion of HIV-1-infected children at the time of choosing the treatment regimens or on the counter-measures against the adverse effects of drugs.

Sex issues in HIV-1-infected persons during highly active antiretroviral therapy: a systematic review.

Science.gov (United States)

Nicastri, Emanuele; Leone, Sebastiano; Angeletti, Claudio; Palmisano, Lucia; Sarmati, Loredana; Chiesi, Antonio; Geraci, Andrea; Vella, Stefano; Narciso, Pasquale; Corpolongo, Angela; Andreoni, Massimo

2007-10-01

Since the introduction of highly active antiretroviral therapy (HAART), morbidity and mortality rates have sharply decreased among HIV-infected patients. Studies of possible differences between men and women in the course of HIV infection give conflicting results. The objective of this study was to assess sex differences during HAART. A literature search by using the MEDLINE database between March 2002 and February 2007 was performed to identify all published studies on the sex-specific differences on the impact of HAART. All articles with measures of effect (preferably adjusted odds ratio, relative risk or hazard ratio with 95% CI) of sex on viroimmunological and clinical parameters during HAART were included. Five different topics of interest in our research were selected: time of initiation of HAART, adherence, viroimmunological response, clinical response and adverse reactions during HAART. US data report an initiation of HAART at an earlier disease stage in men compared with women. After initiation of HAART, most authors do not report any viroimmunological difference, although a few clinical studies showed a significantly better virological response in women compared with men. Nevertheless, women were more likely to be less adherent to antiretrovirals and to have non-structured treatment interruptions than men. This is likely to be related to the higher number of adverse reactions they experience during HAART. Finally, discordant opinions with regard to clinical benefits during HAART exist, but recent clinical and observational trials suggest a better clinical outcome for women. We found little evidence of sex differences during antiretroviral treatment. Nevertheless, most of these studies were underpowered to detect sex differences and had limited follow-up at 6 or 12 months. Design of new gender-sensitive clinical trials with both prolonged follow-up and sample size representative of the current HIV prevalence among women are strongly needed to detect the

Cross-Sectional Analysis of Late HAART Initiation in Latin America and the Caribbean: Late Testers and Late Presenters

Science.gov (United States)

Crabtree-Ramírez, Brenda; Caro-Vega, Yanink; Shepherd, Bryan E.; Wehbe, Firas; Cesar, Carina; Cortés, Claudia; Padgett, Denis; Koenig, Serena; Gotuzzo, Eduardo; Cahn, Pedro; McGowan, Catherine; Masys, Daniel; Sierra-Madero, Juan

2011-01-01

Background Starting HAART in a very advanced stage of disease is assumed to be the most prevalent form of initiation in HIV-infected subjects in developing countries. Data from Latin America and the Caribbean is still lacking. Our main objective was to determine the frequency, risk factors and trends in time for being late HAART initiator (LHI) in this region. Methodology Cross-sectional analysis from 9817 HIV-infected treatment-naïve patients initiating HAART at 6 sites (Argentina, Chile, Haiti, Honduras, Peru and Mexico) from October 1999 to July 2010. LHI had CD4+ count ≤200cells/mm3 prior to HAART. Late testers (LT) were those LHI who initiated HAART within 6 months of HIV diagnosis. Late presenters (LP) initiated after 6 months of diagnosis. Prevalence, risk factors and trends over time were analyzed. Principal Findings Among subjects starting HAART (n = 9817) who had baseline CD4+ available (n = 8515), 76% were LHI: Argentina (56%[95%CI:52–59]), Chile (80%[95%CI:77–82]), Haiti (76%[95%CI:74–77]), Honduras (91%[95%CI:87–94]), Mexico (79%[95%CI:75–83]), Peru (86%[95%CI:84–88]). The proportion of LHI statistically changed over time (except in Honduras) (p≤0.02; Honduras p = 0.7), with a tendency towards lower rates in recent years. Males had increased risk of LHI in Chile, Haiti, Peru, and in the combined site analyses (CSA). Older patients were more likely LHI in Argentina and Peru (OR 1.21 per +10-year of age, 95%CI:1.02–1.45; OR 1.20, 95%CI:1.02–1.43; respectively), but not in CSA (OR 1.07, 95%CI:0.94–1.21). Higher education was associated with decreased risk for LHI in Chile (OR 0.92 per +1-year of education, 95%CI:0.87–0.98) (similar trends in Mexico, Peru, and CSA). LHI with date of HIV-diagnosis available, 55% were LT and 45% LP. Conclusion LHI was highly prevalent in CCASAnet sites, mostly due to LT; the main risk factors associated were being male and older age. Earlier HIV-diagnosis and earlier treatment initiation

Randomised controlled trial examining the effect of exercise in people with rheumatoid arthritis taking anti-TNFα therapy medication.

LENUS (Irish Health Repository)

Reid, Angela

2011-01-01

Substantial progress has been made in the medical management of rheumatoid arthritis (RA) over the past decade with the introduction of biologic therapies, including anti-tumour necrosis factor alpha (anti-TNFα) therapy medications. However, individuals with RA taking anti-TNFα medication continue to experience physical, psychological and functional consequences, which could potentially benefit from rehabilitation. There is evidence that therapeutic exercise should be included as an intervention for people with RA, but to date there is little evidence of the benefits of therapeutic exercise for people with RA on anti-TNFα therapy medication. A protocol for a multicentre randomised controlled three-armed study which aims to examine the effect of dynamic group exercise therapy on land or in water for people with RA taking anti-TNFα therapy medication is described.

Our retroviral heritage.

Science.gov (United States)

Patience, C; Wilkinson, D A; Weiss, R A

1997-03-01

Darwin could not have foretold that we are descended from viruses as well as from apes. While there is clear evidence that viral diseases, such as polio and rabies, affected ancient civilizations, viruses were not defined until the early years of this century, shortly after the rediscovery of mendelian genetics. That retroviral genomes can oscillate between infectious and genetic modes of transmission seemed preposterous before the discovery of reverse transcription in 1970. Those of us who had earlier provided mendelian evidence for germ-line transmission of retroviruses were subject of friendly ridicule. Today, the shunting of genetic elements between chromosomes and RNA, and the generation of processed pseudogenes, seems commonplace. It is timely, however, to revisit the topic of human endogenous retroviruses-the subject of this article.

Circulating anti-retinal antibodies in response to anti-angiogenic therapy in exudative age-related macular degeneration.

Science.gov (United States)

Kubicka-Trząska, Agnieszka; Wilańska, Joanna; Romanowska-Dixon, Bożena; Sanak, Marek

2014-12-01

To determine changes in anti-retinal antibodies (ARAs) during anti-VEGF therapy in patients with exudative age-related macular degeneration (AMD) and to assess the correlations between ARAs and disease activity. The study comprised 98 patients treated with intravitreal bevacizumab. The ophthalmic examination included best corrected visual acuity (BCVA), slit lamp biomicroscopy, fundoscopy, fluorescein angiography (FA), and optical coherence tomography (OCT). Serum ARAs levels were assessed by indirect immunofluorescence (IIF) on normal monkey retina substrate. These studies were repeated at 4 week intervals within 8 months of a follow-up. The sera of 50 sex- and age-matched healthy subjects were used as controls. At baseline examination, 94 (95.5%) of the 98 patients were positive for ARAs. The ARAs titres were significantly higher (p = 0.0000) than in controls. A positive correlation was found between titres of ARAs and the diameter of choroidal neovascularization (CNV) as measured by FA (p = 0.0000), and central retinal thickness (CRT) assessed by OCT (p = 0.0000). A positive correlation was also found between the diameter of CNV, CRT and the complexity of circulating ARAs. Following treatment all patients demonstrated significant decrease in ARAs levels as well as improvement of BCVA, reduction of subretinal fluid on OCT and decreased leakage on FA. Changes in serum ARAs levels occurred in parallel with clinical outcomes of anti-VEGF therapy. Treatment reduced serum levels of ARAs, with the greatest reduction occurring during the 'loading' phase. This study demonstrated that ARAs may act as a serum biomarker of the efficacy of anti-VEGF therapy. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

High-resolution structure of a retroviral protease folded as a monomer

International Nuclear Information System (INIS)

Gilski, Miroslaw; Kazmierczyk, Maciej; Krzywda, Szymon; Zábranská, Helena; Cooper, Seth; Popović, Zoran; Khatib, Firas; DiMaio, Frank; Thompson, James; Baker, David; Pichová, Iva; Jaskolski, Mariusz

2011-01-01

The crystal structure of Mason–Pfizer monkey virus protease folded as a monomer has been solved by molecular replacement using a model generated by players of the online game Foldit. The structure shows at high resolution the details of a retroviral protease folded as a monomer which can guide rational design of protease dimerization inhibitors as retroviral drugs. Mason–Pfizer monkey virus (M-PMV), a D-type retrovirus assembling in the cytoplasm, causes simian acquired immunodeficiency syndrome (SAIDS) in rhesus monkeys. Its pepsin-like aspartic protease (retropepsin) is an integral part of the expressed retroviral polyproteins. As in all retroviral life cycles, release and dimerization of the protease (PR) is strictly required for polyprotein processing and virion maturation. Biophysical and NMR studies have indicated that in the absence of substrates or inhibitors M-PMV PR should fold into a stable monomer, but the crystal structure of this protein could not be solved by molecular replacement despite countless attempts. Ultimately, a solution was obtained in mr-rosetta using a model constructed by players of the online protein-folding game Foldit. The structure indeed shows a monomeric protein, with the N- and C-termini completely disordered. On the other hand, the flap loop, which normally gates access to the active site of homodimeric retropepsins, is clearly traceable in the electron density. The flap has an unusual curled shape and a different orientation from both the open and closed states known from dimeric retropepsins. The overall fold of the protein follows the retropepsin canon, but the C α deviations are large and the active-site ‘DTG’ loop (here NTG) deviates up to 2.7 Å from the standard conformation. This structure of a monomeric retropepsin determined at high resolution (1.6 Å) provides important extra information for the design of dimerization inhibitors that might be developed as drugs for the treatment of retroviral infections

Effect of Nadir CD4+ T cell count on clinical measures of periodontal disease in HIV+ adults before and during immune reconstitution on HAART.

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Lance T Vernon

Full Text Available The contribution of HIV-infection to periodontal disease (PD is poorly understood. We proposed that immunological markers would be associated with improved clinical measures of PD.We performed a longitudinal cohort study of HIV-infected adults who had started highly active antiretroviral therapy (HAART 0mm, clinical attachment level (CAL ≥ 4.0mm, and bleeding on probing (BOP at ≥ 4 sites/tooth and microbiologically as specific periodontopathogen concentration. Linear mixed-effects models were used to assess the associations between immune function and PD.Forty (40 subjects with median 2.7 months on HAART and median nadir CD4+ T-cell count of 212 cells/μl completed a median 3 visits. Over 24 months, CD4+ T-cell count increased by a mean 173 cells/µl (p<0.001 and HIV RNA decreased by 0.5 log10 copies/ml (p<0.001; concurrently, PPD, CAL and BOP decreased by a mean 11.7%, 12.1%, and 14.7% respectively (all p<0.001. Lower nadir CD4+ T-cell count was associated with worse baseline REC (-6.72%; p=0.04 and CAL (9.06%; p<0.001. Further, lower nadir CD4+ T-cell count was associated with a greater relative longitudinal improvement in PPD in subjects with higher baseline levels of Porphyromonas gingivalis (p=0.027, and BOP in subjects with higher baseline levels of Porphyromonas gingivalis or Treponema denticola (p=0.001 and p=0.006 respectively. Longitudinal changes from baseline in CD4+ T-cell count and level of HIV RNA were not independently associated with longitudinal changes in any clinical markers of PD.Degree of immunosuppression was associated with baseline gingival recession. After HAART initiation, measures of active PD improved most in those with lower nadir CD4+ T-cell counts and higher baseline levels of specific periodontopathogens. Nadir CD4+ T-cell count differentially influences periodontal disease both before and after HAART in HIV-infected adults.

The Immune Pathogenesis of Immune Reconstitution Inflammatory Syndrome Associated with Highly Active Antiretroviral Therapy in AIDS

Science.gov (United States)

Zhou, Huaying; He, Yan; Chen, Zi; He, Bo; He, Mei

2014-01-01

Abstract The present study investigated the immunological pathogenesis of immune reconstitution inflammatory syndrome (IRIS) in acquired immunodeficiency syndrome (AIDS) patients undergoing highly active antiretroviral therapy (HAART). A total of 238 patients with AIDS who received initial HAART were included in this prospective cohort study. Blood samples were collected immediately, at baseline, at week 12, and at week 24 after initial HAART and at the onset of IRIS. Lymphocyte subsets, Th1 and Th2 cytokines, and interleukin (IL)-7 levels were measured by flow cytometry or ELISA. Among the 238 patients with AIDS who received HAART, 47 patients developed IRIS. The percentages of CD4+ and CD8+ naive, memory, and activated cells exhibited no significant differences between AIDS patients with and without IRIS 24 weeks after initial HAART. The percentage of CD4+CD25+Foxp3+ regulatory T cells was lower in IRIS patients than in non-IRIS patients before HAART, 12 weeks after HAART, 24 weeks after HAART, and at the onset of IRIS. IL-2 and interferon (IFN)-γ levels were significantly higher at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. In contrast, IL-4 and IL-10 levels were significantly lower at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. Plasma IL-7 decreased gradually with the progression of HAART. The level of IL-7 was higher in IRIS patients than in non-IRIS patients at all follow-up time points. An imbalance of Th1/Th2 cytokines, a consistently low CD+CD25+Fox3+ percentage, and a high IL-7 level may be crucial in the pathogenesis of IRIS in AIDS patients who had received HAART. PMID:25131160

Physical activity and HIV in sub-Saharan Africa: a systematic review ...

African Journals Online (AJOL)

2018-06-02

Jun 2, 2018 ... Background: Self-management strategies such as physical activity (PA) can address disability and optimize mental, ... been scaled up, while anti-retroviral therapy has become ...... Archives of Gerontology and Geriatrics. 2014 ...

All projects related to uganda | Page 9 | IDRC - International ...

International Development Research Centre (IDRC) Digital Library (Canada)

Panafrican Research Agenda on the Integration of ICTs in Education - Phase I ... Developer Network : Open Source Personal Digital Assistant Software for ... the anti-retroviral therapy in Free State province, South Africa (102411); Uganda ...

The optimal management of anti-thrombotic therapy after valve replacement: certainties and uncertainties.

Science.gov (United States)

Iung, Bernard; Rodés-Cabau, Josep

2014-11-07

Anti-thrombotic therapy after valve replacement encompasses a number of different situations. Long-term anticoagulation of mechanical prostheses uses vitamin K antagonists with a target international normalized ratio adapted to the characteristics of the prosthesis and the patient. The association of low-dose aspirin is systematic in the American guidelines and more restrictive in the European guidelines. Early heparin therapy is frequently used early after mechanical valve replacement, although there are no precise recommendations regarding timing, type, and dose of drug. Direct oral anticoagulants are presently contraindicated in patients with mechanical prosthesis. The main advantage of bioprostheses is the absence of long-term anticoagulant therapy. Early anticoagulation is indicated after valve replacement for mitral bioprostheses, whereas aspirin is now favoured early after bioprosthetic valve replacement in the aortic position. Early dual antiplatelet therapy is indicated after transcatheter aortic valve implantation, followed by single antiplatelet therapy. However, this relies on low levels of evidence and optimization of anti-thrombotic therapy is warranted in these high-risk patients. Although guidelines are consistent in most instances, discrepancies and the low-level of evidence of certain recommendations highlight the need for further controlled trials, in particular with regard to the combination of antiplatelet therapy with oral anticoagulant and the early post-operative anti-thrombotic therapy following the procedure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

NARCIS (Netherlands)

Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

2010-01-01

OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

Autoimmune hepatitis in HIV: Case report | Kamau | East African ...

African Journals Online (AJOL)

We present a middle aged lady positive HIV who developed liver disease one year after initiation of anti-retroviral therapy (ART). Laboratory and histo pathology finding supported a diagnosis of autoimmune hepatitis (AIH). She responded well to immuno-suppressive therapy and is currently doing well on maintenance ...

Non-invasive imaging for studying anti-angiogenic therapy effects

NARCIS (Netherlands)

Ehling, J.; Lammers, Twan Gerardus Gertudis Maria; Kiessling, F.

2013-01-01

Noninvasive imaging plays an emerging role in preclinical and clinical cancer research and has high potential to improve clinical translation of new drugs. This article summarises and discusses tools and methods to image tumour angiogenesis and monitor anti-angiogenic therapy effects. In this

Lipodystrophy syndrome associated with antiretroviral therapy in HIV patients: considerations for psychosocial aspects Síndrome de la lipodistrofia asociado con la terapia antiretroviral en pacientes con VIH: consideraciones para los aspectos psicosociales Sindrome da lipodistrofia associada com a terapia anti-retroviral em portadores do HIV: considerações para os aspectos psicossociais

Directory of Open Access Journals (Sweden)

Ana Paula Morais Fernandes

2007-10-01

son necesarios para entender mejor este complejo síndrome, proveyendo nueva información para ser utilizada en el cuidado de enfermería para pacientes con VIH que están afectados por este problema.Diversos efeitos colaterais têm sido associados à terapia anti-retroviral em portadores da infecção pelo HIV, dentre esses, a síndrome da lipodistrofia apresentando hiperlipidemia e alterações na forma do corpo, com hipertrofia adiposa central e lipoatrofia periférica, relatada pelos pacientes como um visível marcador para a identificação de portadores da infecção pelo HIV. Este estudo consiste em análise da produção científica sobre aspectos psicossociais em portadores da infecção pelo HIV que apresentam lipodistrofia associada à utilização da terapia anti-retroviral. Os resultados mostram que alterações corporais podem ser suficientemente perturbadoras para o bem-estar psicossocial, afetando a qualidade de vida e aumentando o estigma da doença, ocasionando perturbações nas relações sociais. Esta revisão possibilita uma análise preliminar dos aspectos psicossocias da lipodistrofia; entretanto, outros estudos são necessários para o melhor entendimento desta complexa síndrome, trazendo novas informações a serem utilizadas no cuidado de enfermagem a portadores da infecção pelo HIV afetados por este problema.

HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis

DEFF Research Database (Denmark)

May, M; Sterne, J; Costagliola, D

2006-01-01

BACKGROUND: Highly active antiretroviral therapy (HAART) for the treatment of HIV infection was introduced a decade ago. We aimed to examine trends in the characteristics of patients starting HAART in Europe and North America, and their treatment response and short-term prognosis. METHODS: We......, 1998, 1999, 2000, 2001, and 2002-03. The primary endpoints were the hazard ratios for AIDS and for death from all causes in the first year of HAART, which were estimated using Cox regression. RESULTS: The proportion of heterosexually infected patients increased from 20% in 1995-96 to 47% in 2002...

Effectiveness and cost of treatment with maraviroc in HIV infection

Directory of Open Access Journals (Sweden)

Viola Sacchi

2009-12-01

Full Text Available Since 1995, life expectancy and quality of life of HIV patients improved significantly due to the use of Highly Active Anti-Retroviral Therapy (HAART, consisting of different combinations of three classes of antiretroviral agents, nucleoside and non-nucleoside reverse transcriptase inhibitors, and protease inhibitors. Recently, new treatment options for individuals developing resistance to these drugs have become available, with the appearance of new drug classes like integrase inhibitors, fusion inhibitors and CCR5 antagonists. Maraviroc is the first antiretroviral agent belonging to the latter drug class approved for clinical use. CCR5 receptor antagonists act by blocking the interaction of the HIV virus with the CCR5 chemokine receptor, a co-receptor essential to the entry process of R5-tropic viruses. The drug is indicated, in combination with other antiretroviral products, for treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable virus strains. Results of main phase III clinical trials indicate that maraviroc, in combination with optimized background therapy (OBT, causes significantly greater reductions in viral load and increases in CD4+ cell count, as compared to OBT alone in this kind of patients. In Italy, the monthly cost of maraviroc therapy is about € 780. A number of economic evaluations, performed for different settings, demonstrate that the therapy including maraviroc is cost-effective if compared to OBT alone, determining an ICER generally below the threshold of three times the GDP per capita. In the Italian context, the ICER determined by OBT + maraviroc vs OBT alone is approximately 45,000 €/LYG.

Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

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Way-Seah Lee

2017-10-01

Full Text Available Anti-tumor necrosis factor (anti-TNF is highly effective in inflammatory bowel disease (IBD; however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years. All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia. All 3 patients died within 1 year from the onset of the infection(s. We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

Science.gov (United States)

Lytle, Allison M; Brown, Harrison C; Paik, Na Yoon; Knight, Kristopher A; Wright, J Fraser; Spencer, H Trent; Doering, Christopher B

2016-01-01

Immune responses to coagulation factors VIII (FVIII) and IX (FIX) represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC) retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV)-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV) vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV. PMID:26909355

Lipid nano-bubble combined with ultrasound for anti-keloids therapy.

Science.gov (United States)

Wang, Xiao Qing; Li, Zhou-Na; Wang, Qi-Ming; Jin, Hong-Yan; Gao, Zhonggao; Jin, Zhe-Hu

2018-03-01

Keloids were characterized by excessive growth of fibrous tissues, and shared several pathological characteristics with cancer. They did put physical and emotional stress on patients in that keloids could badly change appearance of patients. N-(4-hydroxyphenyl) retinamide (4HPR) showed cytotoxic activity on a wide variety of invasive-growth cells. Our work was aim to prepare N-(4-hydroxyphenyl) retinamide-loaded lipid microbubbles (4HPR-LM) combined with ultrasound for anti-keloid therapy. 4HPR-loaded liposomes (4HPR-L) were first prepared by film evaporation method, and then 4HPR-LM were manufactured by mixing 4HPR-L and perfluoropentane (PFP) with ultrasonic cavitation method. The mean particle size and entrapment efficiency 4HPR-LM were 113 nm and 95%, respectively. The anti-keloids activity of 4HPR-LM was assessed with BALB/c nude mice bearing subcutaneous xenograft keloids model. 4HPR-LM, combined with ultrasound, could significantly induce apoptosis of keloid fibroblasts in vitro and inhibited growth of keloids in vivo. Thus, 4HPR-LM could be considered as a promising agent for anti-keloids therapy.

(ReThinking the Corporeality of HIV/AIDS in the Post-HAART Era: A Critical Perspective

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MARILOU GAGNON

2009-06-01

Full Text Available The goal of this paper is to expose the hidden facet of the interface technology-body through a theoretical application of the concept of pharmakon to the fi eld of HIV/AIDS. Based on the works of Plato and Jacques Derrida, the concept of pharmakon is explored and situated within the interface technology-body. Thus, the main objective of this theoretical piece is to discuss how HIV medications as pharmakon are involved in the creation of new forms of corpo/reality for people living with HIV/AIDS, namely the cyborg and the mutant. Inspired by Haraway’s cyborg and Cronenberg’s mutants, the ambivalent quality of technology is explored through the technological fi gure and the monstrous fi gure, two different but complementary representations that expose the bodily experiences of Highly Active Antiretroviral Therapy (HAART.

Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study testing antibodies, RNA and Genotype of HCV in Baghdad.

Science.gov (United States)

Al-Kubaisy, Waqar; Daud, Suzanna; Al-Kubaisi, Mustafa Waseem; Al-Kubaisi, Omar Waseem; Abdullah, Nik Nairan

2018-04-30

Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV

Biomarkers for Anti-Angiogenic Therapy in Cancer

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Markus Wehland

2013-04-01

Full Text Available Angiogenesis, the development of new vessels from existing vasculature, plays a central role in tumor growth, survival, and progression. On the molecular level it is controlled by a number of pro- and anti-angiogenic cytokines, among which the vascular endothelial growth factors (VEGFs, together with their related VEGF-receptors, have an exceptional position. Therefore, the blockade of VEGF signaling in order to inhibit angiogenesis was deemed an attractive approach for cancer therapy and drugs interfering with the VEGF-ligands, the VEGF receptors, and the intracellular VEGF-mediated signal transduction were developed. Although promising in pre-clinical trials, VEGF-inhibition proved to be problematic in the clinical context. One major drawback was the generally high variability in patient response to anti-angiogenic drugs and the rapid development of therapy resistance, so that, in total, only moderate effects on progression-free and overall survival were observed. Biomarkers predicting the response to VEGF-inhibition might attenuate this problem and help to further individualize drug and dosage determination. Although up to now no definitive biomarker has been identified for this purpose, several candidates are currently under investigation. This review aims to give an overview of the recent developments in this field, focusing on the most prevalent tumor species.

New Onset of Dermatomyositis/Polymyositis during Anti-TNF-α Therapies: A Systematic Literature Review

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Alexandra Maria Giovanna Brunasso

2014-01-01

Full Text Available We performed a systematic search of databases from 1990 to 2013 to identify articles concerning the new onset of dermatomyositis/polymyositis (DM/PM in patients treated with anti-TNF-α therapy. We retrieved 13 publications describing 20 patients where the new onset of DM/PM after anti-TNF-α therapy was recorded. 17 patients were affected by rheumatoid arthritis (RA, one by Crohn’s disease, one by ankylosing spondilytis, and one by seronegative arthritis. In 91% of the cases antinuclear autoantibodies were detected after the introduction of anti-TNF-α therapy. In 6 patients antisynthetase antibodies were detected and other clinical findings as interstitial lung disease (ILD were recorded. Improvement of DM/PM after anti-TNF suspension (with the concomitant use of other immunosuppressors was recorded in 94% of cases. The emergence of DM/PM and antisynthetase syndrome seem to be associated with the use of anti-TNF-α agents, especially in patients with chronic inflammatory diseases (mainly RA with positive autoantibodies before therapy initiation. In particular, physicians should pay attention to patients affected by RA with positive antisynthetase antibodies and/or history of ILD. In those cases, the use of the TNF-α blocking agents may trigger the onset of PM/DM or antisynthetase syndrome or may aggravate/trigger the lung disease.

Associated oral lesions in human immunodefeciency virus infected children of age 1 to 14 years in anti retroviral therapy centers in Tamil Nadu

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R Krishna Kumar

2013-01-01

Full Text Available Aim: To evaluate the prevalence of oral lesions status in human immunodeficiency virus (HIV infected children of age 1 to 14 years in Anti Retro viral therapy (ART centres in Tamil Nadu. Materials and Methods: A of total 326 HIV infected children, age 1 to 14 years of which 174 male children and 152 female children were examined for Oral lesions in the Department of Pedodontics and Preventive Dentistry, Rajah Muthiah Dental College and Hospital, Annamalai University in association with the ART centers in Villupuram, Vellore and HIV Homes in Thiruvannamalai, Trichy and Salem in Tamil Nadu towns. Statistical Analysis: Statistical Package for Social Science for Windows (version 11 code: 3000135939012345. Result: Of the total 326 children, 201 (61.65% had oral lesions. (68 [20.86%] with Oral Candidiasis [OC], 54 [16.56%] with Angular Cheilitis, 27 [8.28%] with Necrotizing Ulcerative Gingivitis [NUG], 25 [7.66%] with Necrotizing Ulcerative Periodontitis [NUP], 18 [5.53%] with Linear Gingival Erythema [LGE] and 9 [2.76%] with Apthous Ulcer. Conclusion Among the oral lesions in HIV infected children, OC 20.86% was the predominant oral lesion followed by Angular Chelitis 16.56%, NUG 8.28%, NUP 7.66%, LGE5.53% and Apthous Ulcer 2.76%.

Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

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John F. Flynn

2009-01-01

Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies

Science.gov (United States)

Kohandel, M.; Kardar, M.; Milosevic, M.; Sivaloganathan, S.

2007-07-01

Tumors cannot grow beyond a certain size (about 1-2 mm in diameter) through simple diffusion of oxygen and other essential nutrients into the tumor. Angiogenesis, the formation of blood vessels from pre-existing vessels, is a crucial and observed step, through which a tumor obtains its own blood supply. Thus, strategies that interfere with the development of this tumor vasculature, known as anti-angiogenic therapy, represent a novel approach to controlling tumor growth. Several pre-clinical studies have suggested that currently available angiogenesis inhibitors are unlikely to yield significant sustained improvements in tumor control on their own, but rather will need to be used in combination with conventional treatments to achieve maximal benefit. Optimal sequencing of anti-angiogenic treatment and radiotherapy or chemotherapy is essential to the success of these combined treatment strategies. Hence, a major challenge to mathematical modeling and computer simulations is to find appropriate dosages, schedules and sequencing of combination therapies to control or eliminate tumor growth. Here, we present a mathematical model that incorporates tumor cells and the vascular network, as well as their interplay. We can then include the effects of two different treatments, conventional cytotoxic therapy and anti-angiogenic therapy. The results are compared with available experimental and clinical data.

The prevalence, clinical features, risk factors and outcome ...

African Journals Online (AJOL)

%), neck stiffness 76 (69%) and weight loss 53 (48%). Factors independently associated with CM were male sex, headache, blurred vision and previous antifungal drug use. Night sweats and current use of anti-retroviral therapy were ...

Home delivery of medication - the role of a patient information leaflet on maximising service uptake.

Science.gov (United States)

Watson, L; Ahmed, N; Mccall, H; Minton, J; Benn, P; Edwards, S; Waters, L

2014-12-01

There are currently over 30,000 HIV-positive individuals in London and over 25,000 on anti-retroviral therapy. In 2009/2010, this equated to £170m spent by London's NHS on anti-retroviral drugs. Ways employed to reduce this cost include standardising the drugs patients are on and delivering medication to patients at home. Home delivery (HD) medication is exempt from value-added tax. The savings made from 10 patients using the home delivery service would free up resources to provide anti-retroviral therapy to one further patient. Studies have shown that concerns surrounding potential breaches of confidentiality are a potential barrier to some people using the home delivery service. In order to challenge these concerns, a leaflet was devised highlighting the major benefits to both the patient and the NHS of home delivery and addressing concerns over confidentiality. The leaflet was handed out to patients at the Mortimer Market Centre who were currently on anti-retroviral medication but not on home delivery. They were asked to complete a survey on their views of the service before and after reading the leaflet, whether they had been previously aware of the service and whether their concerns had been addressed. Some 79% felt that the patient information leaflet addressed all of their concerns, and it helped 11% decide whether to consider using home delivery. However, as more patients were opposed to the service after reading the patient information leaflet than those considering it, more work needs to be done to explore patients' concerns and other factors influencing home delivery service uptake. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

[Anti-FGF23 antibody therapy for patients with tumor-induced osteomalacia].

Science.gov (United States)

Kinoshita, Yuka; Fukumoto, Seiji

2014-08-01

Tumor-induced osteomalacia (TIO) is a disease caused by fibroblast growth factor 23 (FGF23) secreted from the causative tumor. This disease is cured by complete surgical removal of the tumor. However, there are several difficult cases in which the responsible tumors cannot be found, are incompletely removed, or relapse after the surgery. Anti-FGF23 antibody is being studied as a novel therapy for FGF23-related hypophosphatemic diseases. The efficacy of anti-FGF23 antibodies were confirmed using a murine model of X-linked hypophosphatemic rickets (XLHR) , which is the most common heritable form of FGF23-related hypophosphatemic disease. In addition, results of phase I study of single injection of humanized anti-FGF23 antibody for adult patients with XLHR were recently published and the safety and effectiveness of this antibody was shown. This antibody therapy may be useful for patients with TIO with similar pathogenesis to that of XLHR.

Luminometric method for screening retroviral protease inhibitors

Czech Academy of Sciences Publication Activity Database

Horáková, D.; Rumlová, Michaela; Pichová, Iva; Ruml, Tomáš

2005-01-01

Roč. 345, č. 1 (2005), s. 96-101 ISSN 0003-2697 R&D Projects: GA AV ČR(CZ) IAA4055304; GA MŠk(CZ) 1M0508; GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z40550506 Keywords : retroviral protease * inhibitors * luminescent assay Subject RIV: CE - Biochemistry Impact factor: 2.670, year: 2005

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.

Retroviral restriction and dependency factors in primates and carnivores

Science.gov (United States)

Fadel, Hind J.; Poeschla, Eric M.

2014-01-01

Recent studies have extended the rapidly developing retroviral restriction factor field to cells of carnivore species. Carnivoran genomes, and the domestic cat genome in particular, are revealing intriguing properties vis-à;-vis the primate and feline lentiviruses, not only with respect to their repertoires of virus-blocking restriction factors but also replication-enabling dependency factors. Therapeutic application of restriction factors is envisioned for human immunodeficiency virus (HIV) disease and the feline immunodeficiency virus (FIV) model has promise for testing important hypotheses at the basic and translational level. Feline cell-tropic HIV-1 clones have also been generated by a strategy of restriction factor evasion. We review progress in this area in the context of what is known about retroviral restriction factors such as TRIM5alpha, TRIMCyp, APOBEC3 proteins and BST-2/Tetherin. PMID:21715018

Risk factors for Kaposi's sarcoma in human immunodeficiency virus patients after initiation of antiretroviral therapy: A nested case–control study in Kenya

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Rodgers Lupia

2017-12-01

Full Text Available Background/Purpose: This study aimed to evaluate the association between highly active antiretroviral therapy (HAART adherence and development of Kaposi's sarcoma (KS in human immunodeficiency virus (HIV/AIDS patients. Methods: We conducted a retrospective nested case–control study of 165 participants (33 cases and 132 controls receiving HAART care at Maseno Hospital, Kenya, from January 2005 to October 2013. Cases were HIV-positive adults with KS, who were matched with controls in a ratio of 1:4 based on age (±5 years of each case, sex, and KS diagnosis date. Perfect adherence to HAART was assessed on every clinic visit by patients' self-reporting and pill counts. Chi-square tests were performed to compare socioeconomic and clinical statuses between cases and controls. A conditional logistic regression was used to assess the effects of perfect adherence to HAART, the latest CD4 count, education level, distance to health-care facility, initial World Health Organization stage, and number of regular sexual partners on the development of KS. Results: Only 63.6% participants reported perfect adherence, and the control group had a significantly higher percentage of perfect adherence (75.0% than did cases (18.2%. After adjustment for potential imbalances in the baseline and clinical characteristics, patients with imperfect HAART adherence had 20-times greater risk of developing KS than patients with perfect HAART adherence [hazard ratios: 21.0, 95% confidence interval: 4.2–105.1]. Patients with low latest CD4 count (≤350 cells/mm3 had a seven-times greater risk of developing KS than did their counterparts (HRs: 7.1, 95% CI: 1.4–36.2. Conclusion: Imperfect HAART adherence and low latest CD4 count are significantly associated with KS development. Keywords: antiretroviral therapy, highly active antiretroviral therapy, human immunodeficiency virus/AIDS treatment, Kaposi's sarcoma, Kenya, Maseno

Predictors of psychological well-being in a diverse sample of HIV-positive patients receiving highly active antiretroviral therapy.

Science.gov (United States)

Safren, Steven A; Radomsky, Adam S; Otto, Michael W; Salomon, Elizabeth

2002-01-01

The purpose of the present study was to identify variables relevant to psychological well-being in HIV patients receiving highly active antiretroviral therapy (HAART). Multiple stressors accompany living with HIV while managing a HAART regimen. However, a variety of cognitive and behavioral variables can protect against or augment the deleterious effects of stress in this population. The authors hypothesized that satisfaction with social support, coping styles, and maladaptive attributions about HIV would explain more variance in psychological well-being than stressful life events per se. Participants were individuals with HIV receiving antiretroviral therapy-either starting a new HAART regimen or having difficulties adhering to their current regimen. Satisfaction with social support, coping styles, and punishment beliefs about HIV were uniquely associated with depression, quality of life, and self-esteem over and above the effects of stressful life events. These results provide support for continued psychosocial interventions that target these variables among patients with HIV.

file 7

African Journals Online (AJOL)

Knowledge of HIV/AIDS by the respondents was related to their level of educational attainment and their professions. ..... therapy if they tested positive even though anti-retroviral drugs. (35.5%) of the ..... Knowledge is power: voluntary HIV ...

Evolution of HVR-1 quasispecies after 1-year treatment in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy.

Science.gov (United States)

Solmone, Mariacarmela; Girardi, Enrico; Lalle, Eleonora; Abbate, Isabella; D'Arminio Monforte, Antonella; Cozzi-Lepri, Alessandro; Alessandrini, Anna; Piscopo, Rita; Ebo, Francesca; Cosco, Lucio; Antonucci, Giorgio; Ippolito, Giuseppe; Capobianchi, Maria R

2006-01-01

Hepatitis C virus (HCV) variability is mainly attributed to the ability of the virus to respond to host immune pressure, acting as a driving force for the evolution of quasispecies. This study was aimed at studying the changes in HVR-1 heterogeneity and the evolution of HCV quasispecies in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy (HAART). Sixteen HIV/HCV-coinfected patients harbouring HCV genotype 1 and who had been on HAART for at least 1 year, 8 showing increasing CD4+ T-cell counts (immunological responders) and 8 showing a stable or decreasing CD4+ T-cell counts (immunological nonresponders), were selected from a prospective cohort study. After 1 year of HAART, 11 patients showed HIV viral load HVR-1 region of HCV. Nonsynonymous/synonymous substitutions ratio (Ka/Ks), aminoacidic complexity (normalized Shannon entropy) and diversity (p-distance), were considered as parameters of quasispecies heterogeneity. After 1 year of HAART, heterogeneity of HVR-1 quasispecies significantly decreased in virological non-responders, whereas the heterogeneity tended to increase in virological responders. The differences in the evolution were less stringent, when considering immunological response. On the other hand, profound qualitative modifications of HVR-1 quasispecies were observed only in patients with both immunological and virological HAART response. On the whole, these findings suggest that, in patients undergoing HAART, the extent of HCV variability and the evolution of HVR-1 quasispecies is influenced by the pattern of response to antiretroviral therapy.

Application of Live-Cell RNA Imaging Techniques to the Study of Retroviral RNA Trafficking

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Darrin V. Bann

2012-06-01

Full Text Available Retroviruses produce full-length RNA that serves both as a genomic RNA (gRNA, which is encapsidated into virus particles, and as an mRNA, which directs the synthesis of viral structural proteins. However, we are only beginning to understand the cellular and viral factors that influence trafficking of retroviral RNA and the selection of the RNA for encapsidation or translation. Live cell imaging studies of retroviral RNA trafficking have provided important insight into many aspects of the retrovirus life cycle including transcription dynamics, nuclear export of viral RNA, translational regulation, membrane targeting, and condensation of the gRNA during virion assembly. Here, we review cutting-edge techniques to visualize single RNA molecules in live cells and discuss the application of these systems to studying retroviral RNA trafficking.

Anti-inflammatory therapy for urinary tract infection in children

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A. A. Vyalkova

2015-01-01

Full Text Available Objective: to substantiate the importance of an etiological approach to diagnosing urinary tract infection in children in terms of the species and biological properties of an infectious agent and to evaluate the efficiency of anti-inflammatory therapy. The study included 116 patients aged 3-15 years with chronic pyelonephritis (Group 1 and isolated bacteriuria (Group 2. After 10-14-day antibiotic therapy, Group 1 patients were allocated to two subgroups: Subgroup la («=30 took furamag 5 mg/kg/day; Subgroup lb («=30 received furamag at the same dose in combination with canephron. The treatment cycle lasted 10-14 days. Subgroup 2a («=26 children had furamag 5 mgДg/day and Subgroup 2b (« =30 took furamag in combination with canephron. The duration of treatment was 14 days. The investigators established the high efficiency of therapy with furamag for renal infection in the children with the active and decrement phases and that of the drug of choice for its monotherapy of isolated highly virulent bacteriuria. Therapeutic efficiency was proven to be related to the species and biological characteristics of an infectious agent. Anti-inflammatory therapy for pyelonephritis in terms of the species of pathogenic bacteria was ascertained to improve the efficiency of treatment. A rationale was provided for the individual choice of antibiotics, followed by the use of furamag, eubiotics, and drugs aimed at inhibiting virulence factors and persistence of the pathogen to sanitize the primary focus of infection.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Science.gov (United States)

Jat, Kana R; Walia, Dinesh K; Khairwa, Anju

2018-03-18

Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018. Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. Only one

Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism

DEFF Research Database (Denmark)

Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki

2016-01-01

The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore size...

Magnitude and correlates of moderate to severe anemia among ...

African Journals Online (AJOL)

Introduction: Moderate to severe anemia is an important clinical problem in HIV patients on Highly Active Antiretroviral Therapy. The rate of progression and mortality in this sub group of patients is high compared to non anemic patients. In sub Saharan Africa with scale up of Anti retroviral therapy, the magnitude of this ...

Research

African Journals Online (AJOL)

ebutamanya

2016-02-04

Feb 4, 2016 ... Abstract. Introduction: Moderate to severe anemia is an important clinical problem in HIV patients on Highly Active Antiretroviral Therapy. The rate of progression and mortality in this sub group of patients is high compared to non anemic patients. In sub Saharan Africa with scale up of Anti retroviral therapy ...

Anti-tumor effects of Egr-IFN gamma gene therapy combined with {sup 125}I-UdR radionuclide therapy

Energy Technology Data Exchange (ETDEWEB)

Jingguo, Zhao [No.403 Hospital of PLA, Dalian (China); Yanjun, Ni; Xiangfu, Song; Yanyi, Li; Wei, Yang; Ting, Sun; Qingjie, Ma; Fengtong, Gao

2008-12-15

Objective: To explore the anti-tumor effects of Egr-IFNgamma gene therapy combined with {sup 125}I-UdR radionuclide therapy in mice bearing H22 hepatocarcinoma and its mechanism. Methods: The recombinant plasmid pcDNAEgr-IFNgamma mixed with liposome was injected into tumor. 48 h later, 370 kBq {sup 125}I-UdR was injected into tumor. The tumor growth rates at different times were observed. After 3 d gene-radionuclide therapy, the concentration of IFNgamma in cytoplasm of H22 cells and cytotoxic activities of splenic CTL of the mice in different groups were examined. Results: The tumor growth rates of pcDNAEgr-IFNgamma + {sup 125}I-UdR group were obviously lower than those of control group, {sup 125}I-UdR group and pcDNAEgr-1 + {sup 125}I-UdR group 6-15 d after gene-radionuclide therapy. IFNgamma protein was found in cytoplasm of H22 cells in pcDNAEgr-IFNgamma + {sup 125}I-UdR group after 3 d gene-radionuclide therapy. Cytotoxic activity of splenic CTL in pcDNAEgr-IFNgamma + {sup 125}I-UdR group was significantly higher than that in the other groups (P<0.01). Conclusions: The anti-tumor effects in vivo of pcDNAEgr-IFNgamma gene therapy combined with {sup 125}I-UdR radionuclide therapy are better than those of {sup 125}I-UdR therapy. (authors)

Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors

International Nuclear Information System (INIS)

Pugach, Pavel; Ketas, Thomas J.; Michael, Elizabeth; Moore, John P.

2008-01-01

The small molecule CCR5 inhibitors are a new class of drugs for treating infection by human immunodeficiency virus type 1 (HIV-1). They act by binding to the CCR5 co-receptor and preventing its use during HIV-1-cell fusion. Escape mutants can be raised against CCR5 inhibitors in vitro and will arise when these drugs are used clinically. Here, we have assessed the responses of CCR5 inhibitor-resistant viruses to other anti-retroviral drugs that act by different mechanisms, and their sensitivities to neutralizing antibodies (NAbs). The rationale for the latter study is that the resistance pathway for CCR5 inhibitors involves changes in the HIV-1 envelope glycoproteins (Env), which are also targets for NAbs. The escape mutants CC101.19 and D1/85.16 were selected for resistance to AD101 and vicriviroc (VVC), respectively, from the primary R5 HIV-1 isolate CC1/85. Each escape mutant was cross-resistant to other small molecule CCR5 inhibitors (aplaviroc, maraviroc, VVC, AD101 and CMPD 167), but sensitive to protein ligands of CCR5: the modified chemokine PSC-RANTES and the humanized MAb PRO-140. The resistant viruses also retained wild-type sensitivity to the nucleoside reverse transcriptase inhibitor (RTI) zidovudine, the non-nucleoside RTI nevirapine, the protease inhibitor atazanavir and other attachment and fusion inhibitors that act independently of CCR5 (BMS-806, PRO-542 and enfuvirtide). Of note is that the escape mutants were more sensitive than the parental CC1/85 isolate to a subset of neutralizing monoclonal antibodies and to some sera from HIV-1-infected people, implying that sequence changes in Env that confer resistance to CCR5 inhibitors can increase the accessibility of some NAb epitopes. The need to preserve NAb resistance may therefore be a constraint upon how escape from CCR5 inhibitors occurs in vivo

Reporter gene expression in fish following cutaneous infection with pantropic retroviral vectors.

Science.gov (United States)

Paul, T A; Burns, J C; Shike, H; Getchell, R; Bowser, P R; Whitlock, K E; Casey, J W

2001-06-01

A central issue in gene delivery systems is choosing promoters that will direct defined and sustainable levels of gene expression. Pantropic retroviral vectors provide a means to insert genes into either somatic or germline cells. In this study, we focused on somatic cell infection by evaluating the activity of 3 promoters inserted by vectors into fish cell lines and fish skin using pantropic retroviruses. In bluegill and zebrafish cell lines, the highest levels of luciferase expression were observed from the 5' murine leukemia virus long terminal repeat of the retroviral vector. The Rous sarcoma virus long terminal repeat and cytomegalovirus early promoter, as internal promoters, generated lower levels of luciferase. Luciferase reporter vectors infected zebrafish skin, as measured by the presence of viral DNA, and expressed luciferase. We infected developing walleye dermal sarcomas with retroviral vectors to provide an environment with enhanced cell proliferation, a condition necessary for integration of the provirus into the host genome. We demonstrated a 4-fold to 7-fold increase in luciferase gene expression in tumor tissue over infections in normal walleye skin.

HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy.

Science.gov (United States)

De Vuyst, Hugo; Lillo, Flavia; Broutet, Nathalie; Smith, Jennifer S

2008-11-01

The objective of this study was to review the literature on the epidemiological association between human papillomavirus (HPV), HIV, and cervical neoplasia, and the impact of highly active antiretroviral therapy (HAART) on this association. MEDLINE was searched using the terms 'human papillomavirus', 'HPV', 'HIV', 'cervix', 'neoplasm', and 'antiretroviral' to identify articles published before December 2006. HIV-infection was strongly associated with a higher prevalence, incidence, and persistence of HPV infection and correlated with prevalence, incidence, persistence, and progression of squamous intraepithelial lesions. The association between HIV and invasive cervical carcinoma has been more difficult to establish, but is now fully recognized. HAART seems to have little, if any, beneficial effect on the natural history of intraepithelial lesions in HIV-positive women. Despite this fact, HAART, does increase the life expectancy of HIV-positive women. Therefore, it remains important to closely monitor HPV-related disease in women with HIV who are receiving HAART, particularly in regions of the world where cervical screening is not available routinely.

Antiretroviral therapy programme outcomes in Tshwane district ...

African Journals Online (AJOL)

Objectives. To ascertain patient retention on ART after 5 years on treatment in one district of Gauteng Province, SA, establish the number of patients ... A retrospective cohort study of patients initiated on highly active antiretroviral therapy (HAART) between January and March .... ferred-out patients from the total of 381 leaves.

Self-perception of knowledge and adherence reflecting the effectiveness of antiretroviral therapy

Directory of Open Access Journals (Sweden)

Dagli-Hernandez C

2016-09-01

-report (SMAQ during monthly drug refill, since it allows monitoring adherence through pharmaceutical assistance. Therefore, patient adherence to HAART could be evaluated using self-perception (CEAT-VIH and the viral load test. Keywords: health literacy, anti-HIV agents, patient compliance, antiretroviral therapy, highly active, acquired immunodeficiency syndrome

Anti-lipopolysaccharide toxin therapy for whole body X-irradiation overdose

Energy Technology Data Exchange (ETDEWEB)

Gaffin, S.L.; Wells, M.; Jordan, J.P.

1985-09-01

Death in humans from ionising radiation overexposure in the 3-8 Gy (300-800 rad) range is in part due to the toxaemia caused by the entry of gram-negative bacteria and/or their lipopolysaccharide toxin (LPS) into the blood circulation through the walls of partially denuded gut. Anti-LPS hyperimmune equine plasma was evaluated for its ability to lower irradiation-induced lethality. Mice were irradiated with 6.3 Gy (630 rad) and six days later received equine Anti-LPS hyperimmune plasma, control plasma or saline. Mortalities in the three groups were 58%, 92% and 79% (p < 0.01) respectively. Thus Anti-LPS may prove useful as an adjunct to conventional therapy in treating radiation sickness.

Anti-lipopolysaccharide toxin therapy for whole body X-irradiation overdose

International Nuclear Information System (INIS)

Gaffin, S.L.; Wells, M.; Jordan, J.P.

1985-01-01

Death in humans from ionising radiation overexposure in the 3-8 Gy (300-800 rad) range is in part due to the toxaemia caused by the entry of gram-negative bacteria and/or their lipopolysaccharide toxin (LPS) into the blood circulation through the walls of partially denuded gut. Anti-LPS hyperimmune equine plasma was evaluated for its ability to lower irradiation-induced lethality. Mice were irradiated with 6.3 Gy (630 rad) and six days later received equine Anti-LPS hyperimmune plasma, control plasma or saline. Mortalities in the three groups were 58%, 92% and 79% (p<0.01) respectively. Thus Anti-LPS may prove useful as an adjunct to conventional therapy in treating radiation sickness. (author)

Model of socio-cultural dimensions involved in adherence to antiretroviral therapy for HIV/AIDS in public health care centers in Chile.

Science.gov (United States)

Stuardo Ávila, Valeria; Manriquez Urbina, Jose Manuel; Fajreldin Chuaqui, Valentina; Belmar Prieto, Julieta; Valenzuela Santibáñez, Victoria

2016-11-01

In Chile, over 14,000 adults are living with HIV receive antiretroviral therapy (HAART). Adequate adherence to HAART has a major impact on survival. There is little consensus on the causes of poor adherence, due to the unique and diverse sociocultural parameters involved in the issue. The objective of this study was to identify sociocultural dimensions that serve as barriers or facilitators to HAART adherence among persons living with HIV/AIDS (PLHIV) in Chile. A qualitative study design, with an exploratory followed by a descriptive phase was conducted. The study population consisted of adults living with HIV/AIDS, with and without HAART. A theoretical sample was designed and three gender profiles defined: women, men, and transwomen. Data collection methods included in-depth interviews by anthropologists in seven public health care centers for PLHIV. The model of sociocultural dimensions indicated that factors associated with family, expectations, gender/sexuality, affect, relationship with HIV, HAART, work, social support and networks, and stigma and discrimination influenced adherence, with different patterns among profiles. This study found that adherence is a dynamic category. It is crucial to consider sociocultural factors in developing strategies to improve HAART adherence.

Clinical features and effect of antiviral therapy on anti-liver/kidney microsomal antibody type 1 positive chronic hepatitis C.

Science.gov (United States)

Ferri, Silvia; Muratori, Luigi; Quarneti, Chiara; Muratori, Paolo; Menichella, Rita; Pappas, Georgios; Granito, Alessandro; Ballardini, Giorgio; Bianchi, Francesco B; Lenzi, Marco

2009-06-01

Anti-liver/kidney microsomal antibody type 1 (anti-LKM1), a serological marker of type 2 autoimmune hepatitis, is also detected in a small proportion of patients with hepatitis C. This study aimed to evaluate clinical features and effect of antiviral therapy in patients with hepatitis C who are anti-LKM1 positive. Sixty consecutive anti-LKM1 positive and 120 age and sex-matched anti-LKM1 negative chronic hepatitis C patients were assessed at diagnosis and during follow-up. Of these, 26 anti-LKM1 positive and 72 anti-LKM1 negative received antiviral therapy. Anti-LKM1 was detected by indirect immunofluorescence and immunoblot. Number of HCV-infected hepatocytes and intrahepatic CD8+ lymphocytes was determined by immunohistochemistry. At diagnosis anti-LKM1 positive patients had higher IgG levels and more intrahepatic CD8+ lymphocytes (p 0.022 and 0.046, respectively). Viral genotypes distribution and response to therapy were identical. Hepatic flares during antiviral treatment only occurred in a minority of patients in concomitance with anti-LKM1 positivity. Immune system activation is more pronounced in anti-LKM1 positive patients with hepatitis C, possibly representing the expression of autoimmune mechanisms of liver damage. Antiviral treatment is as beneficial in these patients as in anti-LKM1 negative patients, and the rare necroinflammatory flares are effectively controlled by corticosteroids, allowing subsequent resumption of antiviral therapy.

Selected anti-tumor vaccines merit a place in multimodal tumor therapies

Energy Technology Data Exchange (ETDEWEB)

Weiss, Eva-Maria; Wunderlich, Roland [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Ebel, Nina [Department of Process Technology and Machinery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Rubner, Yvonne [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Schlücker, Eberhard [Department of Process Technology and Machinery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Meyer-Pittroff, Roland [Competence Pool Weihenstephan, Technische Universität München, Freising (Germany); Ott, Oliver J.; Fietkau, Rainer; Gaipl, Udo S.; Frey, Benjamin, E-mail: benjamin.frey@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany)

2012-10-09

Multimodal approaches are nowadays successfully applied in cancer therapy. Primary locally acting therapies such as radiotherapy (RT) and surgery are combined with systemic administration of chemotherapeutics. Nevertheless, the therapy of cancer is still a big challenge in medicine. The treatments often fail to induce long-lasting anti-tumor responses. Tumor recurrences and metastases result. Immunotherapies are therefore ideal adjuncts to standard tumor therapies since they aim to activate the patient's immune system against malignant cells even outside the primary treatment areas (abscopal effects). Especially cancer vaccines may have the potential both to train the immune system against cancer cells and to generate an immunological memory, resulting in long-lasting anti-tumor effects. However, despite promising results in phase I and II studies, most of the concepts finally failed. There are some critical aspects in development and application of cancer vaccines that may decide on their efficiency. The time point and frequency of medication, usage of an adequate immune adjuvant, the vaccine's immunogenic potential, and the tumor burden of the patient are crucial. Whole tumor cell vaccines have advantages compared to peptide-based ones since a variety of tumor antigens (TAs) are present. The master requirements of cell-based, therapeutic tumor vaccines are the complete inactivation of the tumor cells and the increase of their immunogenicity. Since the latter is highly connected with the cell death modality, the inactivation procedure of the tumor cell material may significantly influence the vaccine's efficiency. We therefore also introduce high hydrostatic pressure (HHP) as an innovative inactivation technology for tumor cell-based vaccines and outline that HHP efficiently inactivates tumor cells by enhancing their immunogenicity. Finally studies are presented proving that anti-tumor immune responses can be triggered by combining RT with selected

Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

Science.gov (United States)

Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

2016-09-01

We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

Perfis de causas múltiplas de morte relacionadas ao HIV/AIDS nos municípios de São Paulo e Santos, Brasil, 2001 Profiles of multiple causes of death related to HIV/AIDS in the cities of São Paulo and Santos, Brazil, 2001

Directory of Open Access Journals (Sweden)

Claudia Cristina de Aguiar Pereira

2007-03-01

Full Text Available Após a introdução da terapia anti-retroviral de alta potência (TARV, o perfil da morbimortalidade relacionada ao HIV alterou-se, passando de óbitos causados por doenças oportunistas para quadros mórbido-crônicos de doenças "pré-AIDS", ou não definidoras de AIDS, causadas pelos efeitos adversos da terapia. Investigou-se a mortalidade relacionada ao HIV/AIDS através das causas múltiplas de morte, utilizando-se as declarações de óbito de residentes nos municípios de São Paulo e Santos, Brasil, que faleceram de causas relacionadas à doença pelo HIV em 2001. Utilizou-se o método Grade of Membership (GoM, que possibilitou criar perfis de causas de morte. Foram encontrados três perfis de mortalidade: o primeiro, relacionado às causas de morte identificadas no período pré-TARV, com predominância de doenças oportunistas; no segundo, houve uma mistura de características do período pré e pós-TARV; o terceiro perfil, residual, não contemplou a doença pelo HIV, mas incorporou grupos de causas de morte associadas aos períodos pré e pós-TARV. Espera-se que este estudo contribua para a elaboração de políticas direcionadas à adequação dos serviços de saúde ao novo cenário de morbimortalidade relacionada ao HIV.Following the introduction of highly active antiretroviral therapy (HAART, the HIV-related morbidity-mortality profile has changed. Opportunistic infections are not as prevalent as before, and "pre-AIDS" diseases have become more common, related mostly to the side effects of HAART. This study focused on HIV/AIDS-related mortality, based on multiple causes of death among individuals who died of HIV-related causes in the cities of São Paulo and Santos, Brazil, in 2001. Grade of Membership (GoM analysis was used. Three mortality profiles were detected: (1 causes of death normally observed before the introduction of HAART, marked by opportunistic infections; (2 causes of death with mixed characteristics, both pre

Anti-EGFR immunonanoparticles containing IL12 and salmosin genes for targeted cancer gene therapy.

Science.gov (United States)

Kim, Jung Seok; Kang, Seong Jae; Jeong, Hwa Yeon; Kim, Min Woo; Park, Sang Il; Lee, Yeon Kyung; Kim, Hong Sung; Kim, Keun Sik; Park, Yong Serk

2016-09-01

Tumor-directed gene delivery is of major interest in the field of cancer gene therapy. Varied functionalizations of non-viral vectors have been suggested to enhance tumor targetability. In the present study, we prepared two different types of anti-EGF receptor (EGFR) immunonanoparticles containing pDNA, neutrally charged liposomes and cationic lipoplexes, for tumor-directed transfection of cancer therapeutic genes. Even though both anti-EGFR immunonanoparticles had a high binding affinity to the EGFR-positive cancer cells, the anti-EGFR immunolipoplex formulation exhibited approximately 100-fold higher transfection to the target cells than anti-EGFR immunoliposomes. The lipoplex formulation also showed a higher transfection to SK-OV-3 tumor xenografts in mice. Thus, IL12 and/or salmosin genes were loaded in the anti-EGFR immunolipoplexes and intravenously administered to mice carrying SK-OV-3 tumors. Co-transfection of IL12 and salmosin genes using anti-EGFR immunolipoplexes significantly reduced tumor growth and pulmonary metastasis. Furthermore, combinatorial treatment with doxorubicin synergistically inhibited tumor growth. These results suggest that anti-EGFR immunolipoplexes containing pDNA encoding therapeutic genes could be utilized as a gene-transfer modality for cancer gene therapy.

Hemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis in the setting of Acquired Immunodeficiency Syndrome (AIDS).

Science.gov (United States)

Asanad, Samuel; Cerk, Brendan; Ramirez, Veronica

2018-06-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disease involving immune system over-activation leading to hemophagocytosis. HLH requires early diagnosis and prompt treatment initiation, especially in patients with Acquired Immunodeficiency Syndrome (AIDS). We present a case of a middle-aged male with AIDS and renal failure, who developed HLH secondary to disseminated histoplasmosis. Etoposide chemotherapy as recommended by the HLH 2004 Guidelines was deferred and treatment focused instead on anti-fungal therapy. Anti-retroviral therapy followed thereafter.

Semiquantitative dynamic computed tomography to predict response to anti-platelet therapy in acute cerebral infarction

International Nuclear Information System (INIS)

Chokyu, K.; Shimizu, K.; Fukumoto, M.; Mori, T.; Mokudai, T.; Mori, K.

2002-01-01

We investigated whether dynamic computed tomography (CT) in patients with acute cerebral infarction could identify patients likely to respond to anti-platelet therapy. Seventy patients underwent semiquantitative dynamic CT within 6 h as well as cerebral angiography. All then received anti-platelet therapy with a thromboxane A2 synthetase inhibitor. Peak value (pv) and time-to-peak (tp) (time-density curves) for the Sylvian fissure were extracted from dynamic CT data and standardizing interpatient data, two indices, PV/TP index and TP index, were prepared following a standard semiquantitative manner. Both PV/TP index and TP index were effective in discriminating between 48 responders (modified Rankin scale (mRS): 0 to 2) and 22 non-responders (mRS: 3 to 5, or death: 6; both P 1.1) and non-compensated rCBF. Intermediate PV/TP values could not predict outcome. Dynamic CT prior to therapy can identify patients with acute cerebral infarction who are treatable with anti-platelet therapy alone. (orig.)

Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

Directory of Open Access Journals (Sweden)

Sloan Derek J

2008-12-01

Full Text Available Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Guillain-Barré syndrome presenting as acute inflammatory demyelinating polyneuropathy in a 30-year-old man testing positive for Immunodeficiency Virus, probably during acute seroconversion. Clinical suspicion was confirmed by cerebrospinal fluid analysis and nerve conduction studies. Rapid clinical deterioration prompted intravenous immunoglobulin therapy and early commencement of highly active anti-retroviral therapy. All symptoms resolved within nine weeks. Conclusion Unusual neurological presentations in previously fit patients are an appropriate indication for Immunodeficiency-Virus testing. Highly active anti-retroviral therapy with adequate penetration of the central nervous system should be considered as an early intervention, alongside conventional therapies such as intravenous immunoglobulin.

Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

Science.gov (United States)

Matusali, G.; Dereuddre-Bosquet, N.; Le Tortorec, A.; Moreau, M.; Satie, A.-P.; Mahé, D.; Roumaud, P.; Bourry, O.; Sylla, N.; Bernard-Stoecklin, S.; Pruvost, A.; Le Grand, R.

2015-01-01

ABSTRACT A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian immunodeficiency virus mac251 (SIVmac251) who were treated for 4 months with HAART, which was intensified over the last 7 weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen or in testis, epididymis, seminal vesicles, and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA-positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of nonproductively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly in the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organ infection in long-term-treated infected individuals. IMPORTANCE A substantial subset of men receiving prolonged HAART suppressing viral loads in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV

Enteric parasitic infections in HIV/AIDS patients before and after the highly active antiretroviral therapy

Directory of Open Access Journals (Sweden)

Tatiana Paschoalette Rodrigues Bachur

Full Text Available Enteroparasites are related to gastrointestinal alterations among patients with HIV/AIDS, some causing severe manifestations in the period before the institution of the highly active antiretroviral therapy (HAART. The prevalence of enteroparasitoses in patients with HIV/AIDS seen at two hospitals in Ceará , Brazil, was compared in the pre-HAART (Group 1; n = 482 and HAART (Group 2; n = 100 eras. Fecal parasitologic examinations (FPE were performed using the direct, Lutz, Baermann-Moraes and modified Ziehl-Neelsen methods. The following parasites were detected in Groups 1 and 2, respectively: Strongyloides stercoralis - 30.1% and 11% (p<0.0001, Ascaris lumbricoides - 15.6% and 2% (p<0.0001, hookworms - 13.7% and 2% (p<0.0001, Trichuris trichiura - 13.1% and 1% (p<0.0001, Hymenolepis nana - 0 and 1% (p = 0.1718, Giardia duodenalis - 7.9% and 1% (p = 0.0076, Entamoeba histolytica/dispar - 3.3% and 1% (p = 0.3301, Isospora belli - 4.8% and 1% (p = 0.0993, Cryptosporidium sp. - 8.1% and 0 (p = 0.0007, and non-pathogenic protozoans as well. There was a significant reduction in the prevalence of enteroparasites between the eras (63.9% to 24%; p<0.0001. In the HAART era, the following observations were made: greater frequency of enteroparasites in patients without antiretroviral therapy (p = 0.0575, as in those with AIDS (p = 0.08, and diarrhea (36% of the patients; lack of association with positive FPE (p = 0.626; and non-detection of Cryptosporidium sp. Strongyloides stercoralis showed an elevated prevalence in the two eras and was more frequent in men (32.41% than women (19.04% of Group 1 (p = 0.018, a finding suggesting the transmission of the helminth through sodomy. The advent of the HAART modified the profile of opportunistic infections, including parasites, probably due to the reconstitution of cellular immunity and the direct action of HAART on the parasites.

Case Report HeLs malnourished o admit him to the nutrition unit ...

African Journals Online (AJOL)

and vocal resonance on the left side, anterior and posterior, with reduced breath ... hint that she may have been the source of the child's HIV infection, before, during or ... child's HIV status? Has either of them been on anti-retroviral therapy?

Assessment of precision and concordance of quantitative mitochondrial DNA assays: a collaborative international quality assurance study

NARCIS (Netherlands)

Hammond, Emma L.; Sayer, David; Nolan, David; Walker, Ulrich A.; Ronde, Anthony de; Montaner, Julio S. G.; Cote, Helene C. F.; Gahan, Michelle E.; Cherry, Catherine L.; Wesselingh, Steven L.; Reiss, Peter; Mallal, Simon

2003-01-01

Background: A number of international research groups have developed DNA quantitation assays in order to investigate the role of mitochondrial DNA depletion in anti-retroviral therapy-induced toxicities. Objectives: A collaborative study was undertaken to evaluate intra-assay precision and between

Inflammatory and coagulation biomarkers and mortality in patients with HIV infection

DEFF Research Database (Denmark)

Kuller, Lewis H; Tracy, Russell; Belloso, Waldo

2008-01-01

BACKGROUND: In the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug conservation [DC]) than continuous ART (viral suppression [VS]).We hypothesized that increased...

Anti-vascular endothelial growth factor therapy-induced glioma invasion is associated with accumulation of Tie2-expressing monocytes

Science.gov (United States)

Hossain, Mohammad B.; Conrad, Charles A.; Aldape, Kenneth D.; Fuller, Gregory N.; Marini, Frank C.; Alonso, Marta M.; Idoate, Miguel Angel; Gilbert, Mark R.; Fueyo, Juan; Gomez-Manzano, Candelaria

2014-01-01

The addition of anti-angiogenic therapy to the few treatments available to patients with malignant gliomas was based on the fact that these tumors are highly vascularized and on encouraging results from preclinical and clinical studies. However, tumors that initially respond to this therapy invariably recur with the acquisition of a highly aggressive and invasive phenotype. Although several myeloid populations have been associated to this pattern of recurrence, a specific targetable population has not been yet identified. Here, we present evidence for the accumulation of Tie2-expressing monocytes/macrophages (TEMs) at the tumor/normal brain interface of mice treated with anti-VEGF therapies in regions with heightened tumoral invasion. Furthermore, we describe the presence of TEMs in malignant glioma surgical specimens that recurred after bevacizumab treatment. Our studies showed that TEMs enhanced the invasive properties of glioma cells and secreted high levels of gelatinase enzymatic proteins. Accordingly, Tie2+MMP9+ monocytic cells were consistently detected in the invasive tumor edge upon anti-VEGF therapies. Our results suggest the presence of a specific myeloid/monocytic subpopulation that plays a pivotal role in the mechanism of escape of malignant gliomas from anti-VEGF therapies and therefore constitutes a new cellular target for combination therapies in patients selected for anti-angiogenesis treatment. PMID:24809734

Bio markers and Anti-EGFR therapies for Krads wild-type tumors in metastatic colorectal cancer patients

International Nuclear Information System (INIS)

Diaz Rubio Garcia, E.

2009-01-01

The natural history of metastasis colorectal cancer has being clearly modified in terms of response rate, time to progression and overall survival, once the antiEGFR monoclonal antibodies (cetuximab and panitumumab) have emerged in combination with the standard cytotoxic chemotherapy (FOLFOX and FOLFIRI). However, the benefit from cetuximab and panitumumab is only confined to KRAS-wild type (KRAS-wt) colorectal tumors, while KRAS mutated tumors do not respond to these drugs. The 65 % of colorectal tumors are KRAS-wt tumors, but efficacy of antiEGFR therapies is detected only in 60-70 % of these KRAS-wt tumors. Other biomarkers and molecular pathways must be involved in the response of the antiEGFR therapies for the KRAS-wt colorectal tumors, such as the EGFR ligands, the EGFR-phosphorilated levels, the number of EGFR copies, the status of the KRAS effected B-RAF and the alternative intracellular signaling pathways PIK3CA/PTEN/AKT and JAK/STAT. A battery of these biomarkers is needed to select the most sensitive patients to the antiEGFR therapies. This pattern may represent a novel favorable cost-effectiveness tool to develop tailored treatments. A review of these biomarkers and molecular pathways, involved in the antiEGFR therapies response, is performed. (Author) 68 refs.

Concise classification of the genomic porcine endogenous retroviral gamma1 load to defined lineages.

Science.gov (United States)

Klymiuk, Nikolai; Wolf, Eckhard; Aigner, Bernhard

2008-02-05

We investigated the infection history of porcine endogenous retroviruses (PERV) gamma1 by analyzing published env and LTR sequences. PERV sequences from various breeds, porcine cell lines and infected human primary cells were included in the study. We identified a considerable number of retroviral lineages indicating multiple independent colonization events of the porcine genome. A recent boost of the proviral load in an isolated pig herd and exclusive occurrence of distinct lineages in single studies indicated the ongoing colonization of the porcine genome with endogenous retroviruses. Retroviral recombination between co-packaged genomes was a general factor for PERV gamma1 diversity which indicated the simultaneous expression of different proviral loci over a period of time. In total, our detailed description of endogenous retroviral lineages is the prerequisite for breeding approaches to minimize the infectious potential of porcine tissues for the subsequent use in xenotransplantation.

A screen to identify drug resistant variants to target-directed anti-cancer agents

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Azam Mohammad

2003-01-01

Full Text Available The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec, a specific inhibitor of the Chronic Myeloid Leukemia (CML-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair.

Diphtheria Antibodies and T lymphocyte Counts in Patients Infected with HIV-1

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Francisco A. B. Speranza

2012-09-01

Full Text Available We assessed the IgG levels anti-diphtheria (D-Ab and T cell counts (CD4+ and CD8+ in HIV-1 infected subjects undergoing or not highly active antiretroviral therapy (HAART. Approximately 70% of all HIV-1 patients were unprotected against diphtheria. There were no differences in D-Ab according to CD4 counts. Untreated patients had higher D-Ab (geometric mean of 0.62 IU/ml than HAART-patients (geometric mean of 0.39 IU/ml. The data indicated the necessity of keeping all HIV-1 patients up-to-date with their vaccination.

Disability and health outcomes - from a cohort of people on long-term anti-retroviral therapy.

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Myezwa, Hellen; Hanass-Hancock, Jill; Ajidahun, Adedayo Tunde; Carpenter, Bradley

2018-12-01

Human-immunodeficiency virus (HIV)/Acquired immunodeficiency Syndrome (AIDS) remains a major health problem in South Africa - even after two decades since the introduction of antiretroviral therapy (ART). Long-term survival with HIV is associated with new health-related issues and a risk of functional limitation/disability. The aim of this study was to assess functional limitation associated with HIV/AIDS among people living with HIV (PLHIV) in South Africa. This study is a cross-sectional survey using a cohort in an urban area in Gauteng province, South Africa. Data were collected using questionnaires through an interview process. The information collected included aspects such as demographics, livelihood, the state of mental and physical health, adherence and disability. A total of 1044 participants with an average age of 42 ± 12 years were included in the study, with 51.9% of the participants reporting functional limitations (WHODAS ≥ 2). These were reported mainly in the domains of participation (40.2%) and mobility (38.7%). In addition, adherence to ART, symptoms of poor physical health and depression were strongly associated with their functional limitations/disability. HIV as a chronic disease is associated with functional limitations that are not adequately addressed and pose a risk of long-term disability and negative adherence outcomes. Therefore, wellness for PLHIV/AIDS needs to include interventions that can prevent and manage disability.

Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

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Allison M Lytle

2016-01-01

Full Text Available Immune responses to coagulation factors VIII (FVIII and IX (FIX represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV.

Immunological Response of Hiv-Infected Children to Highly Active Antiretoviral Therapy at Gondar University Hospital, North-Western Ethiopia.

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Kokeb, Mehretie; Degu, Getu

2016-01-01

The effectiveness of highly active antiretroviral therapy (HAART) in children has not been well studied specially in developing countries where the burden of HIV is high. This study was aimed to assess the immunologic response of HIV-infected children to HAART at Pediatric ART Clinic Gondar University Hospital. Institution based cross-sectional study was conducted at the Pediatric ART Clinic Gondar University Hospital from March 01-April 30, 2014. The study included 283 HIV-infected children who were on HAART for 6 months and above. Medical records of HIV-infected children were reviewed using pre-tested questionnaire. CD4 count/percent was collected every 6 months retrospectively. For all statistical significance tests, the cut-off value was pimmunological response. The study revealed that there was good Immunological response to ART, and that the maximum response was in the 1(st) 6 months of ART. Low CD4 count at initiation, undisclosed HIV status and lack of good adherence were found to cause low immunological response to HAART.

Risk Factors of Clinical and Immunological Failure in South Indian Cohort on Generic Antiretroviral Therapy.

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Sadashiv, Mucheli Shravan; Rupali, Priscilla; Manesh, Abi; Kannangai, Rajesh; Abraham, Ooriapadickal Cherian; Pulimood, Susanne A; Karthik, Rajiv; Rajkumar, S; Thomas, Kurien

2017-12-01

Since the time of NACO Antiretroviral (ART) roll-out, generic ART has been the mainstay of therapy. There are many studies documenting the efficacy of generic ART but with the passage of time, failure of therapy is on the rise. As institution of second line ART has significant financial implications both for a program and for an individual it is imperative that we determine factors which contribute towards treatment failure in a cohort of patients on generic antiretroviral therapy. This was a nested matched case-control study assessing the predictors for treatment failure in our cohort who had been on Anti-retroviral therapy for at least a year. We identified 42 patients (Cases) with documented treatment failure out of our cohort of 823 patients and 42 sex, age and duration of therapy-matched controls. Using a structured proforma, we collected information from the out-patient and in-patient charts of the Infectious Diseases clinic Cohort in CMC, Vellore. A set of predetermined variables were studied as potential risk factors for treatment failure on ART. Univariate analysis showed significant association with 1) Self-reported nonadherenceART and thus help development of targeted interventions.

Perforated Gastric Ulcer Associated with Anti-Angiogenic Therapy

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Diogo Libânio

2017-08-01

Full Text Available Anti-angiogenic therapy with bevacizumab, an inhibitor of vascular endothelial growth factor, is commonly used in metastatic colorectal cancer and is rarely associated with gastrointestinal perforation, perforation being more frequent in the primary tumor site or at the anastomotic level. We present the case of a 64-year-old male with stage IV rectal adenocarcinoma who was on palliative chemotherapy with FOLFOX and bevacizumab. After the 4th chemotherapy cycle, our patient started fever and epigastric pain. He was hemodynamically stable, and signs of peritoneal irritation were absent. There were no alterations in the abdominal X-ray, and C-reactive protein was markedly elevated. A CT scan revealed a de novo thickness in the gastric antrum. Upper digestive endoscopy showed an ulcerated 40-mm lesion in the angulus, with a 20-mm orifice communicating with an exsudative cavity revested by the omentum. A conservative approach was decided including fasting, broad-spectrum intravenous antibiotics, and proton-pump inhibitors. Subsequent gastroduodenal series showed no contrast extravasation, allowing the resumption of oral nutrition. Esophagogastroduodenoscopy after 8 weeks showed perforation closure. Biopsies did not show neoplastic cells or Heliobacter pylori infection. Although the success in the conservative management of perforation allowing the maintenance of palliative chemotherapy (without bevacizumab, the patient died after 4 months due to liver failure. The reported case shows an uncommon endoscopic finding due to a rare complication of anti-angiogenic therapy. Additionally, it reminds clinicians that a history of gastroduodenal ulcers should be actively sought before starting anti-angiogenic treatment and that suspicion for perforation should be high in these cases.

One-pill once-a-day HAART: a simplification strategy that improves adherence and quality of life of HIV-infected subjects

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Monica Airoldi

2010-05-01

Full Text Available Monica Airoldi1,6, Mauro Zaccarelli2, Luca Bisi3, Teresa Bini4, Andrea Antinori2, Cristina Mussini3, Francesca Bai4, Giancarlo Orofino5, Laura Sighinolfi7, Andrea Gori6, Fredy Suter1, Franco Maggiolo11Division of Infectious Diseases, Ospedali Riuniti, Bergamo; 2Clinical Department, INMI L Spallanzani, Roma; 3Division of Infectious Diseases, Università, Modena; 4Division of Infectious Diseases, Ospedale San Paolo, Milano; 5Division of Infectious Diseases, Ospedale Amedeo di Savoia, Torino; 6Division of Infectious Diseases, Ospedale San Gerardo, Monza; 7Division of Infectious Diseases, Ospedale Sant’Anna, Ferrara, ItalyObjective: The aim of the ADONE (ADherence to ONE pill study was to verify the effect of a reduced number of pills on adherence and quality of life (QoL in HIV-infected patients on highly active antiretroviral therapy (HAART.Design: Prospective, multicenter, study.Methods: Patients chronically treated with emtricitabine (FTC + tenofovir (TDF + efavirenz (EFV or lamivudine (3TC + TDF + EFV and with a HIV-RNA < 50 copies/mL were switched to the single-pill fixed-dose regimen (FDR of FTC + TDF + EFV. Data were collected with SF-36 using visual analog scales. Results of the final (6 months primary as-treated analysis are reported.Results: 212 patients (77.4% males of mean age 45.8 years were enrolled; 202 completed the study. One month post switch to FDR the adherence rate increased significantly to 96.1% from a baseline value of 93.8% (P < 0.01. The increase was steadily maintained throughout the study (96.2% at 6 months. QoL improved over time from 68.8% to 72.7% (P = 0.042 as well, and was significantly associated with the perception of health status, presence of adverse events (AEs and number of reported AEs (P < 0.0001. QoL significantly influenced adherence (P < 0.0001. During FDR use the mean CD4 count increased from 556 to 605 cells/μL (P < 0.0001. At the end of follow-up 98% of patients maintained HIV-RNA level < 50 copies

Report of AIDS-related lymphoma in South Korea

International Nuclear Information System (INIS)

Kim, Jin-Soo; Kim, Seok-Jin; Kim, Jin-Seok

2008-01-01

The prevalence of acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL) is increasing in South Korea. The aim of this study is to identify the clinical features of ARL in South Korea. From 1998 through 2006, we retrospectively analysed a total of 23 cases of ARL from seven institutions. The patients consisted of 20 males and 3 females at a median age of 40 (range, 20-72) on diagnosis of AIDS. ARL developed at their median age of 41 (range, 24-72). The histological diagnosis was aggressive B cell lymphoma in the majority, but rare T cell and NK/T cell lymphoma were also included. Ten of 23 (43.5%) was receiving highly active anti-retroviral therapy (HAART) before the diagnosis of ARL. Fifteen of twenty-three patients were given combination chemotherapy with/without radiation, four were given radiation alone, and four did not receive any treatment against medical advice. Of 20 patients followed-up, nine were alive in remission, two alive in disease, one died of treatment related complication, four died of progressive lymphoma, four died of AIDS related causes. The response to treatment included complete response (CR) in eight (44.4%), partial response (PR) in four (22.2%) and progressive disease (PD) in three (16.7%). The response to HARRT was evaluable in 13 patients based on CD4+ cell count and human immnodeficiency virus (HIV) viral load, among which nine (69.2%) responded. Estimated median survival time was 43.9 months. Although the population of patients is small, this is the first clinical data analyses of Korean ARL patients. As a substantial portion of the patients remains alive disease free, the impact of HAART on the clinical course of ARL needs further follow-up and evaluation. (author)

Determinants of subjective health status of HIV positive mothers in NAUTH Nnewi.

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Nwabueze, S A; Adogu, P O U; Adinma, E D; Ifeadike, C O; Nnebue, C C; Ilika, A L; Ikechebelu, J I

2012-01-01

Acquired immune deficiency syndrome (AIDS) caused by human immune deficiency virus (HIV), once dominated by infected males has become feminized especially in sub-Saharan Africa where the majority of adults living with the condition are females. Positive life styles, belonging to social support groups and stigma-free HIV services by providers may have good impact on the quality of life of HIV-positive mothers. This study was aimed at assessing the determinants of subjective health status of HIV-positive mothers accessing prevention-of-mother-to-child-transmission (PMTCT) of HIV services in Nnamdi Azikiwe University Teaching Hospital (NAUTH) Nnewi. This is a descriptive study in which 288 consenting HIV positive mothers were selected using the systematic sampling technique. Data on demographics, life style, social support, contraceptive use and subjective feeling about current health status were collected from the subjects using a pre-tested, structured, interviewer-administered questionnaire. The mean age of the respondents was 30.46 +/- 4.86 years. Majority (89.2%) of them were married while 55.2% were traders. A significantly higher proportion of the mothers on highly active anti retroviral therapy (HAART) (70.8%) than non users (29.2%) described their current health status as 'excellent' (p<0.001). Also a significantly higher proportion of condom users (99%) than pill users (1%) described their health status as 'excellent' (p<0.02). The same significantly higher proportions of 'excellent' response were given by subjects who engage in social support activities (p<0.001), who practice good feeding (p<0.01) andpersonal hygiene (p<0.01). Access to family planning services and HAART, participation in support group activities and positive lifestyle practices tend to improve subjective health status and should be comprehensively encouraged among the HIV positive mothers.

Steroids block the anti-inflammatory effects of low level laser therapy

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Lopes-Martins, Rodrigo Alvaro B.; Albertini, Regiane; Lopes-Martins, Patricia Sardinha L.; Iversen, Vegard V.; Bjordal, Jan M.

2006-02-01

Objective: Concomitant use of multiple therapies is common in musculoskeletal and airway disorders. Low level laser therapy (LLLT) is considered a promising therapy in arthritis, tendinopathies and rhinitis. We designed two animal studies to assess if the expected anti-inflammatory effect LLLT could be affected by resection of the adrenal gland or concomitant use of the cortisol antagonist mifepristone. Methods: Two studies were performed, with 40 male Wistar rats and with 40 Balb C male mice respectively.. In both studies, four groups received carrageenan and one control group received saline. At 1, 2, and 3 hours after injections, LLLT irradiation was performed with a dose of 7.5 J/cm2. In the rat study, two of the carrageenan groups had the adrenal gland dissected. In the mice study, two of the carrageenan-injected groups were in addition pre-treated with orally administered mifepristone. Results: In the rat paw study, LLLT reduced edema significantly compared to the carrageenan only group (1.5 vs 0.9 ml, peffect of LLLT could be totally blocked by adding the cortisol antagonist mifepristone ( pSteroid therapy should not be used concomitantly with LLLT, as the anti-inflammatory effect of LLLT is lost if cortisol receptors are downregulated.

Global Journal of Social Sciences - Vol 11, No 1 (2012)

African Journals Online (AJOL)

Cost-Benefit Analysis of Anti-Retroviral Therapy (Art) for HIV/AIDS Treatment and its Economic Implications in Nigeria · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. BE Ndem, CE Bassey, c Otu, 63-72 ...

HIV/AIDS treatment in two Ghanaian hospitals: experiences of patients, nurses and doctors

NARCIS (Netherlands)

Dapaah, J.M.

2012-01-01

Jonathan Mensah Dapaah onderzocht de manier waarop hiv/aids wordt behandeld in Voluntary Counselling and Testing (VCT) centra en Anti Retroviral Therapy (ART) klinieken in twee Ghanese ziekenhuizen. Deze diensten worden steeds toegankelijker, maar het aantal mensen dat ervan gebruik maakt blijft

HIV treatment is associated with a twofold higher probability of raised triglycerides

DEFF Research Database (Denmark)

Ekoru, Kenneth; Young, Elizabeth H; Dillon, David G

2018-01-01

Background: Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations. Methods: Pooled analyses of ...

Outcome of anti-retroviral treatment in HIV-infected orphans and non-orphans at an ART centre in North India.

Science.gov (United States)

Bhattacharya, Malobika; Saxena, Romit

2012-01-01

Few Indian studies have reported the long-term efficacy of anti-retroviral treatment (ART) in children and in orphaned, HIV-infected children in particular. To study differences in outcome of ART in HIV-infected orphans compared with non-orphans. A retrospective study of 87 HIV-infected children who commenced ART in the period January 2006 to August 2007. The main measures were orphan status, absolute CD4 count and weight-for-height (WHZ) and height-for-age (HAZ) Z-scores. Median follow-up was 33 months. Forty (45·9%) children were orphaned. Orphans and non-orphans had similar baseline median WHZ and HAZ (-2·48 vs -2·63, P = 0·65 and -2·78 vs -2·91, P = 0·77, respectively). The two groups were similar in terms of WHO clinical stage and frequency of severe immunosuppression at presentation (P = 0·88 and 0·25, respectively). After ART initiation, the median absolute CD4 count increased progressively in both groups. Median WHZ and HAZ increased throughout the study period in the orphans and reached -1 at 27 and 39 months of ART, respectively. In the non-orphans, WHZ remained below that of the orphan group, the difference becoming statistically significant from 18 months of ART. The increment in HAZ in the non-orphan group was at par with the orphan group until 12 months of follow-up, after which it fell between 18 and 30 months. Subsequently, HAZ rose but remained below that of the orphan group. Both WHZ and HAZ failed to reach -1 in the non-orphan group. In both groups, 85% reported 100% adherence to ART. The outcome of ART is not affected by orphan status with the extended family adequately supporting orphaned children. Growth of children whose parents are HIV-infected may be constrained despite ART if there is inadequate family support.

Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis : A Systematic Review

NARCIS (Netherlands)

Kroesen, Vera M.; Gröschel, Matthias I.; Martinson, Neil; Zumla, Alimuddin; Maeurer, Markus; van der Werf, Tjip S.; Vilaplana, Cristina

2017-01-01

Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs), in contrast, target host factors to mitigate disease severity. In

Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility

NARCIS (Netherlands)

Bosteels, Jan; Weyers, Steven; D'Hooghe, Thomas M.; Torrance, Helen; Broekmans, Frank J.; Chua, Su Jen; Mol, Ben Willem J.

2017-01-01

Background: Observational evidence suggests a potential benefit with several anti-adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of an intrauterine device or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) for decreasing intrauterine

How useful is determination of anti-factor Xa activity to guide bridging therapy with enoxaparin? A pilot study.

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Hammerstingl, Christoph; Omran, Heyder; Tripp, Christian; Poetzsch, Bernd

2009-02-01

Low-molecular-weight heparins (LMWH) are commonly used as peri-procedural bridging anticoagulants. The usefulness of measurement of anti-factor Xa activity (anti-Xa) to guide bridging therapy with LMWH is unknown. It was the objective of this study to determine levels of anti-Xa during standard bridging therapy with enoxaparin, and to examine predictors for residual anti-Xa. Consecutive patients receiving enoxaparin at a dosage of 1 mg/kg body weight/12 hours for temporary interruption of phenprocoumon were prospectively enrolled to the study. Blood-samples were obtained 14 hours after LMWH-application immediately pre- procedurally. Procedural details, clinical and demographic data were collected and subsequently analyzed. Seventy patients were included (age 75.2 +/- 10.8 years, Cr Cl 55.7 +/- 21.7ml/min, body mass index [BMI] 27.1 +/- 4.9). LMWH- therapy was for a mean of 4.2 +/- 1.6 days; overall anti-Xa was 0.58 +/- 0.32 U/ml. In 37 (52.8%) of patients anti-Xa was > or U/ml, including 10 (14.3%) patients with anti-Xa > 1U/ml. Linear regression analysis of single variables and logistic multivariable regression analysis failed to prove a correlation between anti-Xa and single or combined factors. No major bleeding, no thromboembolism and four (5.7%) minor haemorrhages were observed. When bridging OAC with therapeutic doses of enoxaparin a high percentage of patients undergo interventions with high residual anti-Xa. The levels of anti-Xa vary largely and are independent of single or combined clinical variables. Since the anti-Xa-related outcome of patients receiving bridging therapy with LMWH is not investigated, no firm recommendation on the usefulness of monitoring of anti-Xa can be given at this stage.

Retroviral integration: Site matters

Science.gov (United States)

Demeulemeester, Jonas; De Rijck, Jan

2015-01-01

Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success. PMID:26293289

HMGB1/anti-HMGB1 antibodies define a molecular signature of early stages of HIV-Associated Neurocognitive Isorders (HAND

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Marie-Lise Gougeon

2017-02-01

Conclusion: We report that brain injury in chronically HIV-infected patients on stable HAART is strongly associated with persistent CNS inflammation, which is correlated with increased levels of HMGB1 and anti-HMGB1 IgG in the CSF. Moreover, we identified circulating anti-HMGB1 IgG as a very early biomarker of neurological impairment in patients without HAND. These results might have important implication for the identification of patients who are at high risk of developing neurological disorders.

Interpretation US Elastography in Chronic Hepatitis B with or without Anti-HBV Therapy

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Cheng-Han Lee

2017-11-01

Full Text Available Inflammation has significant impacts on liver fibrosis measurement by ultrasound elastography. The interpretation requires further optimization in patients with or without anti-viral therapy. We prospectively enrolled a consecutive series of patients with chronic hepatitis B who received liver histology analysis and acoustic radiation force impulse (ARFI. 146 patients who underwent liver biopsy (50.9% or tumor resection (49.1% were enrolled. 34 patients (23.3% had been receiving anti-hepatitis B therapy of various duration. The areas under the receiver-operating characteristic (AUROC for the diagnosis of Metavir F4 by mean ARFI was 0.820 in the non-treatment group and 0.796 in the treatment group. The ARFI tended to be not lower (100% than the corresponding Metavir grading in patients with treatment within 12 months, equal (75% from 13 to 31 months, and lower (71.4% after 32 months. We conclude that ARFI is a reliable tool for measurement of liver fibrosis in chronic hepatitis B patients with ALT (alanine aminotransferase <5x the upper limit of normal. For those patients under anti-HBV therapy, the optimal timing for ARFI analysis will be over 1–2.5 years of nucleos(tide analogue therapy. The ARFI measurement after 2.5 years tends to be lower than the corresponding histology grading.

Role of anti-angiogenesis therapy in the management of hepatocellular carcinoma: The jury is still out

Institute of Scientific and Technical Information of China (English)

Hong; Sun; Man-Sheng; Zhu; Wen-Rui; Wu; Xiang-De; Shi; Lei-Bo; Xu

2014-01-01

As the leading cause of disease-related deaths,cancer is a major public health threat worldwide.Surgical resection is still the first-line therapy for patients with early-stage cancers.However,postoperative relapse and metastasis remain the cause of 90%of deaths of patients with solid organ malignancies,including hepatocellular carcinoma(HCC).With the rapid development of molecular biology techniques in recent years,molecularly targeted therapies using monoclonal antibodies,small molecules,and vaccines have become a milestone in cancer therapeutic by significantly improv-ing the survival of cancer patients,and have opened a window of hope for patients with advanced cancer.Hypervascularization is a major characteristic of HCC.It has been reported that anti-angiogenic treatments,which inhibit blood vessel formation,are highly effective for treating HCC.However,the efficacy and safety of anti-angiogenesis therapies remain controversial.Sorafenib is an oral multikinase inhibitor with antiproliferative and anti-angiogenic effects and is the first molecular target drug approved for the treatment of advanced HCC.While sorafenib has shown promising therapeutic effects,substantial evidence of primary and acquired resistance to sorafenib has been reported.Numerous clinical trials have been conducted to evaluate a large number of molecularly targeted drugs for treating HCC,but most drugs exhibited less efficacy and/or higher toxicity compared to sorafenib.Therefore,understanding the mechanism(s)underlying sorafenib resistance of cancer cells is highlighted for efficiently treating HCC.This concise review aims to provide an overview of anti-angiogenesis therapy in the management of HCC and to discuss the common mechanisms of resistance to anti-angiogenesis therapies.

Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs

International Nuclear Information System (INIS)

Huang, Hai; Zhou, Wei; Zhu, Haiyan; Zhou, Pei; Shi, Xunlong

2017-01-01

Background: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. Objectives: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance. Methods: The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism. Results and discussion: BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBV rtM204V/rtLl80M transfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1 kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs. - Highlights: • Baicalin benefits the anti-HBV therapy. • Baicalin enhances ETV antiviral efficacy and overcomes NA-resistant HBV mutation. • The anti-HBV effect of baicalin is achieved by inhibiting HBV RNAs. • Baicalin down-regulates HBV replication-dependent host factors HNF 1α and HNF 4α.

Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs

Energy Technology Data Exchange (ETDEWEB)

Huang, Hai, E-mail: HHai3552@sina.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Zhou, Wei, E-mail: zhouw@fudan.edu.cn [Department of Chemistry, Fudan University, 220 Han Dan Road, Shanghai 200433 (China); Zhu, Haiyan, E-mail: haiyanzhu@fudan.edu.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Zhou, Pei, E-mail: pzhou@shmu.edu.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Shi, Xunlong, E-mail: xunlongshi@fudan.edu.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China)

2017-05-15

Background: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. Objectives: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance. Methods: The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism. Results and discussion: BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBV{sup rtM204V/rtLl80M} transfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1 kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs. - Highlights: • Baicalin benefits the anti-HBV therapy. • Baicalin enhances ETV antiviral efficacy and overcomes NA-resistant HBV mutation. • The anti-HBV effect of baicalin is achieved by inhibiting HBV RNAs. • Baicalin down-regulates HBV replication-dependent host factors HNF 1α and HNF 4α.

Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease

International Nuclear Information System (INIS)

Fink, J.K.; Correll, P.H.; Perry, L.K.; Brady, R.O.; Karlsson, S.

1990-01-01

Retroviral gene transfer has been used successfully to correct the glucocerebrosidase (GCase) deficiency in primary hematopoietic cells from patients with Gaucher disease. For this model of somatic gene therapy, the authors developed a high-titer, amphotropic retroviral vector designated NTG in which the human GCase gene was driven by the mutant polyoma virus enhancer/herpesvirus thymidine kinase gene (tk) promoter (Py + /Htk). NTG normalized GCase activity in transduced Gaucher fibroblasts and efficiently infected human monocytic and erythroleukemic cell lines. RNA blot-hybridization (Northern blot) analysis of these hemaptopoietic cell lines showed unexpectedly high-level expression from the Moloney murine leukemia virus long terminal repeat (Mo-MLV LTR) and levels of Py + /Htk enhancer/promoter-initiated human GCase RNA that approximated endogenous GCase RNA levels. Furthermore, NTG efficiently infected human hematopoietic progenitor cells. Detection of the provirus in approximately one-third of NTG-infected progenitor colonies that had not been selected in G418-containing medium indicates that relative resistance to G418 underestimated the actual gene transfer efficiency. Northern blot analysis of NTG-infected, progenitor-derived cells showed expression from both the Mo-MLV LTR and the Py + /Htk enhancer/promoter. NTG-transduced hematopoietic progenitor cells from patients with Gaucher disease generated progeny in which GCase activity has been normalized

Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease

Energy Technology Data Exchange (ETDEWEB)

Fink, J.K.; Correll, P.H.; Perry, L.K.; Brady, R.O.; Karlsson, S. (National Institutes of Health, Bethesda, MD (USA))

1990-03-01

Retroviral gene transfer has been used successfully to correct the glucocerebrosidase (GCase) deficiency in primary hematopoietic cells from patients with Gaucher disease. For this model of somatic gene therapy, the authors developed a high-titer, amphotropic retroviral vector designated NTG in which the human GCase gene was driven by the mutant polyoma virus enhancer/herpesvirus thymidine kinase gene (tk) promoter (Py{sup +}/Htk). NTG normalized GCase activity in transduced Gaucher fibroblasts and efficiently infected human monocytic and erythroleukemic cell lines. RNA blot-hybridization (Northern blot) analysis of these hemaptopoietic cell lines showed unexpectedly high-level expression from the Moloney murine leukemia virus long terminal repeat (Mo-MLV LTR) and levels of Py{sup +}/Htk enhancer/promoter-initiated human GCase RNA that approximated endogenous GCase RNA levels. Furthermore, NTG efficiently infected human hematopoietic progenitor cells. Detection of the provirus in approximately one-third of NTG-infected progenitor colonies that had not been selected in G418-containing medium indicates that relative resistance to G418 underestimated the actual gene transfer efficiency. Northern blot analysis of NTG-infected, progenitor-derived cells showed expression from both the Mo-MLV LTR and the Py{sup +}/Htk enhancer/promoter. NTG-transduced hematopoietic progenitor cells from patients with Gaucher disease generated progeny in which GCase activity has been normalized.

Factors influencing cerebrospinal fluid and plasma HIV-1 RNA detection rate in patients with and without opportunistic neurological disease during the HAART era

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