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Sample records for short-course hiv-prophylactic nevirapine

  1. Nevirapine, sodium concentration and HIV-1 RNA in breast milk and plasma among HIV-infected women receiving short-course antiretroviral prophylaxis

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    Salado-Rasmussen, Kirsten; Theilgaard, Zahra Persson; Chiduo, Mercy G.

    2015-01-01

    and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine). Methods Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks...... postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant. Results HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median...... (interquartile range, IQR) of 1.5 μg/mL (0.75–2.20 μg/mL) and 1.04 μg/mL (0.39–1.71 μg/mL), respectively (P women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 μg/mL (0.13–0.39 μg/mL) and 0.22 μg/mL (0.13–0.34 μg...

  2. Identification of Nevirapine-Resistant HIV-1 in the Latent Reservoir after Single-Dose Nevirapine to Prevent Mother-to-Child Transmission of HIV-1

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    Wind-Rotolo, Megan; Durand, Christine; Cranmer, Lisa; Reid, Alison; Martinson, Neil; Doherty, Meg; Jilek, Benjamin L.; Kagaayi, Joseph; Kizza, Allan; Pillay, Visva; Laeyendecker, Oliver; Reynolds, Steven J.; Eshleman, Susan H.; Lau, Bryan; Ray, Stuart C.; Siliciano, Janet D.; Quinn, Thomas C.; Siliciano, Robert F.

    2009-01-01

    Background Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4+ T cells, potentially complicating future treatment. Methods Blood samples were collected from 60 women from South Africa and Uganda >6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4+ T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance. Results Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women. Conclusions A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment. PMID:19338474

  3. Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated.

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    Aizire, Jim; Fowler, Mary Glenn; Wang, Jing; Shetty, Avinash K; Stranix-Chibanda, Lynda; Kamateeka, Moreen; Brown, Elizabeth R; Bolton, Steve G; Musoke, Philippa M; Coovadia, Hoosen

    2012-01-28

    Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed. Secondary data analysis of the 'HIV Prevention Trials Network-046 protocol' (version 2.0), a phase-III, randomized, placebo-controlled trial that assessed efficacy and safety of nevirapine prophylaxis against breast milk transmission of HIV-1. Trial infants received 6-month study nevirapine/placebo, and standard-of-care peripartum single-dose nevirapine+/- zidovudine 'tail', and cotrimoxazole prophylaxis from 6 weeks through breastfeeding cessation. Adverse events were monitored using United States Division of AIDS Toxicity Tables (2004). Risk of neutropenia, anemia and skin-rash in the cotrimoxazole + nevirapine and the cotrimoxazole + placebo groups were compared using negative-binomial regression. Incidence of neutropenia and/or anemia, and skin-rash was highest during the first 6 weeks of life and declined, thereafter, regardless of study group. Time to first adverse event after 6 weeks was similar in cotrimoxazole + nevirapine and cotrimoxazole + placebo groups: hazard ratio (95% confidence interval) was 1.26 (0.96-1.66) for neutropenia and/or anemia (all grades), 1.27 (0.80-2.03) for neutropenia and/or anemia (grade ≥3) and 1.16 (0.46-2.90) for skin-rash (grade ≥2). There were no statistically significant differences in immediate (6 weeks-6 months) and long-term (6-12 months) adverse event risk among infants on cotrimoxazole + nevirapine versus cotrimoxazole + placebo. Extended nevirapine and cotrimoxazole prophylaxis through 6 months of age among HIV-exposed uninfected infants did not appear to increase the immediate or long-term risk of neutropenia, anemia or skin-rash. Concurrent use beyond 6 months, however, needs to be evaluated.

  4. a study of nevirapine toxicity in hiv infected pregnant women

    African Journals Online (AJOL)

    Esem

    HIV infected women commenced on nevirapine-based regimen in the current pregnancy with CD4 counts up to. 3. 350 cells/mm at the University Teaching Hospital,. Lusaka, Zambia. Design: Longitudinal observational study with 2 arms. Group 1 (low CD4 count arm): HIV infected pregnant. 3 women with CD4 counts less ...

  5. Comparison of nevirapine plasma concentrations between lead-in and steady-state periods in Chinese HIV-infected patients.

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    Huijuan Kou

    Full Text Available To investigate the potential of nevirapine 200 mg once-daily regimen and evaluate the influence of patient characteristics on nevirapine concentrations.This was a prospective, multicentre cohort study with 532 HIV-infected patients receiving nevirapine as a part of their initial antiretroviral therapy. Plasma samples were collected at trough or peak time at the end of week 2 (lead-in period and week 4, 12, 24, 36, and 48 (steady-state period, and nevirapine concentrations were determined using a validated HPLC method. Potential influencing factors associated with nevirapine concentrations were evaluated using univariate and multivariate logistic regression.A total of 2348 nevirapine plasma concentrations were collected, including 1510 trough and 838 peak values. The median nevirapine trough and peak concentration during the lead-in period were 4.26 µg/mL (IQR 3.05-5.61 and 5.07 µg/mL (IQR 3.92-6.44 respectively, which both exceeded the recommended thresholds of nevirapine plasma concentrations. Baseline hepatic function had a moderate effect on median nevirapine trough concentrations at week 2 (4.25 µg/mL v.s. 4.86 µg/mL, for ALT <1.5 × ULN and ≥ 1.5 × ULN, respectively, P = 0.045. No significant difference was observed in median nevirapine trough concentration between lead-in and steady-state periods in patients with baseline ALT and AST level ≥ 1.5 × ULN (P = 0.171, P = 0.769, which was different from the patients with ALT/AST level <1.5ULN. The median trough concentrations were significantly higher in HIV/HCV co-infected patients than those without HCV at week 48 (8.16 µg/mL v.s. 6.15 µg/mL, P = 0.004.The 200 mg once-daily regimen of nevirapine might be comparable to twice-daily in plasma pharmacokinetics in Chinese population. Hepatic function prior to nevirapine treatment and HIV/HCV coinfection were significantly associated with nevirapine concentrations.

  6. High exposure to nevirapine in plasma is associated with an improved virological response in HIV-1-infected individuals

    NARCIS (Netherlands)

    Veldkamp, A. I.; Weverling, G. J.; Lange, J. M.; Montaner, J. S.; Reiss, P.; Cooper, D. A.; Vella, S.; Hall, D.; Beijnen, J. H.; Hoetelmans, R. M.

    2001-01-01

    OBJECTIVE: To explore relationships between exposure to nevirapine and the virological response in HIV-1-infected individuals participating in the INCAS trial. METHODS: The elimination rate constant of plasma HIV-1 RNA (k) was calculated during the first 2 weeks of treatment with nevirapine,

  7. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study.

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    Montaner, J S; Reiss, P; Cooper, D; Vella, S; Harris, M; Conway, B; Wainberg, M A; Smith, D; Robinson, P; Hall, D; Myers, M; Lange, J M

    1998-03-25

    Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA. To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine. Double-blind, controlled, randomized trial. University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada and Australia (INCAS). Antiretroviral therapy-naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60x10(9)/L (200-600/microL). Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine. Plasma HIV-1 RNA. Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death

  8. Detection of HIV drug resistance mutations in pregnant women receiving single dose Nevirapine in south India

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    Mini S Jacob

    2011-01-01

    Full Text Available Background: Single dose of Nevirapine to prevent mother to child transmission of HIV is the commonest preventive regimen in resource-limited countries. Objectives: The objective of this study was to detect drug-resistant virus after single dose of Nevirapine (sdNVP provided to delivering HIV seropositive (HIV+ve women and to evaluate the time taken for its decay. Results: Of the 36 consenting HIV+ve pregnant women enrolled into the study, the mean hemoglobin and total lymphocyte counts were 10.8 g/dl and 1843 cells/mm 3 , respectively. Mean CD4 counts in 64% of women was 363 cells/mm 3 and mean viral load for 16/36 women was 28,143 copies/ml of plasma. Nevirapine-resistance mutations were detected in 28% of women at delivery; using OLA (Oligonucleotide Ligation Assay. K103N mutations were seen in 19.4% of women while the Y181C mutation was seen in 5%. Both the mutations were detected in 2.7% of women. Sequential blood samples collected at delivery, 7-10 days, 6 weeks, 4 months, 6 months and one year postpartum showed that 81% of K103N mutations and 66.7% of Y181C mutations were detected at 6 weeks postpartum . Wild-type virus had replaced the mutants by one year postpartum in all women except one. Conclusion : These observations are relevant for future treatment with antiretroviral therapy in these women for their HIV disease.

  9. The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

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    Sinha Sanjeev

    2011-11-01

    Full Text Available Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV and tuberculosis (TB co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART when co-administered with rifampicin-containing antituberculosis treatment (ATT and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1% patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83 at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10, 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08, 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10 respectively and 3.04 μg/ml (in cases. Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in

  10. Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

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    Ena J

    2012-11-01

    Full Text Available Javier Ena, Concepción Amador, Conxa Benito, Francisco PasquauHIV Unit, Hospital Marina Baixa, Villajoyosa, SpainAbstract: We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase–inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment–naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment–naïve patients, and TRANxITION, a study carried out in antiretroviral treatment–experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.Keywords: nevirapine

  11. [Hepatotoxicity in healthy infants exposed to nevirapine during pregnancy].

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    Iveli, Pablo; Noguera-Julian, Antoni; Soler-Palacín, Pere; Martín-Nalda, Andrea; Rovira-Girabal, Núria; Fortuny-Guasch, Clàudia; Figueras-Nadal, Concepció

    2016-01-01

    The use of nevirapine in HIV-infected pregnant women is discouraged due to its potential to cause hepatotoxicity. There is limited information available on the toxicity in non-HIV infected newborn exposed to this drug during pregnancy. The aim of the study is to determine the extent of hepatotoxicity in the newborn exposed to nevirapine and HIV during pregnancy. A cross-sectional, observational, multicenter study was conducted on a cohort of healthy infants born to HIV-infected mothers, in whom the first determination of alanine aminotransferase (ALT), before 6weeks of age, was collected. Patients were allocated to 2groups according to exposure to nevirapine during pregnancy. Hepatotoxicity was rated according to the AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). This study included 160newborns from 159pregnancies (88exposed to nevirapine-based regimens and 71 exposed to protease inhibitors-based therapies). No cases of hepatotoxicity were observed according to the DAIDS Table for Grading. Two cases of ALT above normal values (2.8%; 95%CI: 0.3-9.8%) were observed in patients not exposed to nevirapine, and one case (1.1%; 95%CI: 0.0-6.1%) in the group exposed to nevirapine (P=.585). The lack of differences between groups suggests that highly active antiretroviral treatment regimens including nevirapine administered during pregnancy do not involve a higher risk of liver disease compared to other treatment combinations. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  12. Electrochemical studies of nevirapine, an anti-HIV drug, and its assay in tablets and biological samples

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    JALDAPPAGARI SEETHARAMAPPA

    2012-06-01

    Full Text Available The electrochemical oxidation of nevirapine, an anti-HIV drug, at a glassy carbon electrode has been studied by voltammetric techniques. Nevirapine showed one well defined irreversible oxidation peak with a potential of 0.749 V in phosphate buffer at pH 10. The effects of different electrolytes, pH and scan rate on the electrochemical behaviour of nevira¬pine were examined to determine the optimum reaction conditions. The oxidation peak current was found to vary linearly with the concentration of nevirapine in the range of 5.0 – 350 µM. The limit of detection and limit of quantification values were calculated and found to be 1.026 µM and 3.420 µM, respectively. The low relative standard deviation values of inter-day and intra-day assays highlighted the good reproducibility of the proposed m¬ethod for assay of nevirapine. Further, a sensitive and accurate differential pulse voltammetric method was developed for the determination of nevirapine concentrations in pharma¬ceutical formulations.

  13. The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals

    NARCIS (Netherlands)

    van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Wit, F. W.; Lange, J. M.; Danner, S. A.; Foudraine, N. A.; Kwakkelstein, M. O.; Reiss, P.; Beijnen, J. H.; Hoetelmans, R. M.

    2000-01-01

    OBJECTIVE: To investigate and to compare the steady-state plasma pharmacokinetics of nevirapine in a dosing regimen of 400 mg once daily versus 200 mg twice daily in HIV-1-infected individuals. DESIGN: Open-label, randomized, cross-over study. METHODS: Twenty HIV-1-infected individuals who already

  14. Toxicogenomics of nevirapine-associated cutaneous and hepatic adverse events among populations of African, Asian, and European descent

    NARCIS (Netherlands)

    Yuan, Jing; Guo, Sheng; Hall, David; Cammett, Anna M.; Jayadev, Supriya; Distel, Manuel; Storfer, Stephen; Huang, Zimei; Mootsikapun, Piroon; Ruxrungtham, Kiat; Podzamczer, Daniel; Haas, David W.; Benetucci, Jorge; Ortega, Gerardo; Cahn, Pedro; Cesar, Carina; Cassetti, Isabel; Bissio, Emiliano; Lupo, Sergio; Chuah, John; Workman, Cassy; Rees, Vanessa; Cooper, David A.; Hickey, Rebecca; Anderson, Jonathan; Moore, Richard; Hoy, Jennifer; Downs, Cath; Finlayson, Robert; Bodsworth, Neil; Eu, Beng; Lau, Helen; Montaner, Julio; Harris, Marianne; Walmsley, Sharon; d'Aquila, Adrianna; Conway, Brian; Tossonian, Harout; Morlat, Philippe; Louis, Isabelle; Yazdanpanah, Yazdan; Ajana, Faiza; Bollens, Diane; Girard, Pierre-Marie; May, Thierry; Pialoux, Gilles; Slama, Laurence; Lyavanc, Thomas; Piketty, Christophe; Reiss, Peter

    2011-01-01

    Nevirapine is widely prescribed for HIV-1 infection. We characterized relationships between nevirapine-associated cutaneous and hepatic adverse events and genetic variants among HIV-infected adults. We retrospectively identified cases and controls. Cases experienced symptomatic nevirapine-associated

  15. Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study.

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    Monera-Penduka, Tsitsi G; Maponga, Charles C; Wolfe, Alan R; Wiesner, Lubbe; Morse, Gene D; Nhachi, Charles F B

    2017-01-01

    Moringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated. Adult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout. Blood sampling was repeated after 14 days of nevirapine and moringa (1.85 g leaf powder/day) co-administration. Nevirapine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. To assess the effect of moringa on nevirapine PK, the change in nevirapine area under the plasma concentration-time curve (AUC) was determined. The mean difference in pre- and post-moringa nevirapine, maximum concentration (C max ) and concentration at 12 h (C 12h ) were also calculated. The PK parameters were compared by assessing the post/pre geometric mean ratios (GMRs) and associated 90% confidence intervals (CIs). Pharmacokinetics analyses were performed on the results from 11 participants for whom complete data were obtained. The post/pre GMRs and associated 90% CIs for nevirapine were 1.07 (1.00-1.14) for the AUC; 1.06 (0.98-1.16) for C max and 1.03 (0.92-1.16) for C 12h . Co-administration of Moringa oleifera Lam. leaf powder at the traditional dose did not significantly alter the steady-state PK of nevirapine. Trial registration number NCT01410058 (ClinicalTrials.gov).

  16. Similar HIV protection from four weeks of zidovudine versus nevirapine prophylaxis among formula-fed infants in Botswana

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    Kathleen M. Powis

    2018-03-01

    Full Text Available Background: The World Health Organization HIV guidelines recommend either infant zidovudine (ZDV or nevirapine (NVP prophylaxis for the prevention of intrapartum motherto-child HIV transmission (MTCT among formula-fed infants. No study has evaluated the comparative efficacy of infant prophylaxis with twice daily ZDV versus once daily NVP in exclusively formula-fed HIV-exposed infants.   Methods: Using data from the Mpepu Study, a Botswana-based clinical trial investigating whether prophylactic co-trimoxazole could improve infant survival, retrospective analyses of MTCT events and Division of AIDS (DAIDS Grade 3 or Grade 4 occurrences of anaemia or neutropenia were performed among infants born full-term (≥ 37 weeks gestation, with a birth weight ≥ 2500 g and who were formula-fed from birth. ZDV infant prophylaxis was used from Mpepu Study inception. A protocol modification mid-way through the study led to the subsequent use of NVP infant prophylaxis.   Results: Among infants qualifying for this secondary retrospective analysis, a total of 695 (52% infants received ZDV, while 646 (48% received NVP from birth for at least 25 days but no more than 35 days. Confirmed intrapartum HIV infection occurred in two (0.29% ZDV recipients and three (0.46% NVP recipients (p = 0.68. Anaemia occurred in 19 (2.7% ZDV versus 12 (1.9% NVP (p = 0.36 recipients. Neutropenia occurred in 28 (4.0% ZDV versus 21 (3.3% NVP recipients (p = 0.47.   Conclusions: Both ZDV and NVP resulted in low intrapartum transmission rates and no significant differences in severe infant haematologic toxicity (DAIDS Grade 3 or Grade 4 among formula-fed full-term infants with a birthweight ≥ 2500 g.

  17. A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

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    Paredes, Roger; Puertas, Maria Carmen; Bannister, Wendy

    2011-01-01

    Background. The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. Methods. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated...... in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI...... = .013). A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. Conclusions. The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure...

  18. 18-month effectiveness of short-course antiretroviral regimens combined with alternatives to breastfeeding to prevent HIV mother-to-child transmission.

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    Valériane Leroy

    Full Text Available OBJECTIVE: We assessed the 18-month effectiveness of short-course (sc antiretroviral peripartum regimens combined with alternatives to prolonged breastfeeding to prevent mother-to-child transmission (MTCT of HIV-1 in Abidjan, Côte d'Ivoire. METHODOLOGY: HIV-1 infected pregnant women received from >/=32-36 weeks of gestation scZidovudine (ZDV+/-Lamivudine (3TC+single-dose Nevirapine (sdNVP at delivery within the ANRS 1201/1202 DITRAME-Plus cohort (2001-2003. Neonates received a sdNVP+7-day ZDV prophylaxis. Two infant-feeding interventions were systematically offered free of charge: formula-feeding or exclusive shortened breastfeeding with early cessation from four months. The reference group was the ANRS 049a DITRAME cohort (1994-2000 exposed to scZDV from 36 weeks, then to prolonged breastfeeding. Pediatric HIV infection was defined by a positive plasma HIV-1 RNA at any age, or if aged >/=18 months, a positive HIV-1 serology. Turnbull estimates of cumulative transmission risks (CTR and effectiveness (HIV-free survival were compared by exposure group using a Cox model. FINDINGS: Among 926 live-born children enrolled, 107 (11.6% were HIV-infected at 18 months. CTRs were 22.3% (95% confidence interval[CI]:16-30% in the 238 ZDV long-term breastfed reference group, 15.9% (CI:10-27% in the 169 ZDV+sdNVP shortened breastfed group; 9.4% (CI:6-14% in the 195 ZDV+sdNVP formula-fed group; 6.8% (CI:4-11% in the 198 ZDV+3TC+sdNVP shortened breastfed group, and 5.6% (CI:2-10% in the 126 ZDV+3TC+sdNVP formula-fed group. Each combination had a significantly higher effectiveness than the ZDV long-term breastfed group except for ZDV+sdNVP shortened breastfed children, ranging from 51% (CI:20-70% for ZDV+sdNVP formula fed children to 63% (CI:40-80% for ZDV+3TC+NVPsd shortened breastfed children, after adjustment for maternal eligibility for antiretroviral therapy (ART, home delivery and low birth-weight. Substantial MTCT risk reductions are reachable in Africa

  19. Reversal of atherogenic lipoprotein profile in HIV-1 infected patients with lipodystrophy after replacing protease inhibitors by nevirapine

    NARCIS (Netherlands)

    Negredo, Eugenia; Ribalta, Josep; Paredes, Roger; Ferré, Raimón; Sirera, Guillem; Ruiz, Lidia; Salazar, Juliana; Reiss, Peter; Masana, Lluís; Clotet, Bonaventura

    2002-01-01

    Background: The widespread use of protease inhibitors (PI) has been associated with abnormalities in the lipid profile of HIV-1-infected patients. Treatment simplification approaches in which PI are replaced by nevirapine (NVP) have been shown to improve PI-related toxicity. Objective: To assess the

  20. Evaluation of nevirapine and/or hydroxyurea with nucleoside reverse transcriptase inhibitors in treatment-naive HIV-1-infected subjects

    NARCIS (Netherlands)

    Blanckenberg, Daniel H.; Wood, Robin; Horban, Andrzej; Beniowski, Marek; Boron-Kaczmarska, Anna; Trocha, Hanna; Halota, Waldemar; Schmidt, Reinhold E.; Fatkenheuer, G.; Jessen, Heiko; Lange, Joep M. A.

    2004-01-01

    Objective: To examine the effect of adding nevirapine (NVP) and/or hydroxyurea (HU) to a triple nucleoside analogue reverse transcriptase inhibitor (NRTI) regimen in terms of efficacy and tolerability. Methods: HIV-1-infected, treatment-naive adults were randomized, using a factorial design, to add

  1. Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study.

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    Patel, Rena C; Onono, Maricianah; Gandhi, Monica; Blat, Cinthia; Hagey, Jill; Shade, Starley B; Vittinghoff, Eric; Bukusi, Elizabeth A; Newmann, Sara J; Cohen, Craig R

    2015-11-01

    Concerns have been raised about efavirenz reducing the effectiveness of contraceptive implants. We aimed to establish whether pregnancy rates differ between HIV-positive women who use various contraceptive methods and either efavirenz-based or nevirapine-based antiretroviral therapy (ART) regimens. We did this retrospective cohort study of HIV-positive women aged 15-45 years enrolled in 19 HIV care facilities supported by Family AIDS Care and Education Services in western Kenya between Jan 1, 2011, and Dec 31, 2013. Our primary outcome was incident pregnancy diagnosed clinically. The primary exposure was a combination of contraceptive method and efavirenz-based or nevirapine-based ART regimen. We used Poisson models, adjusting for repeated measures, and demographic, behavioural, and clinical factors, to compare pregnancy rates among women receiving different contraceptive and ART combinations. 24,560 women contributed 37,635 years of follow-up with 3337 incident pregnancies. In women using implants, adjusted pregnancy incidence was 1.1 per 100 person-years (95% CI 0.72-1.5) for nevirapine-based ART users and 3.3 per 100 person-years (1.8-4.8) for efavirenz-based ART users (adjusted incidence rate ratio [IRR] 3.0, 95% CI 1.3-4.6). In women using depot medroxyprogesterone acetate, adjusted pregnancy incidence was 4.5 per 100 person-years (95% CI 3.7-5.2) for nevirapine-based ART users and 5.4 per 100 person-years (4.0-6.8) for efavirenz-based ART users (adjusted IRR 1.2, 95% CI 0.91-1.5). Women using other contraceptive methods, except for intrauterine devices and permanent methods, had 3.1-4.1 higher rates of pregnancy than did those using implants, with 1.6-2.8 higher rates in women using efavirenz-based ART. Although HIV-positive women using implants and efavirenz-based ART had a three-times higher risk of contraceptive failure than did those using nevirapine-based ART, these women still had lower contraceptive failure rates than did those receiving all other

  2. The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda

    NARCIS (Netherlands)

    Bartelink, Imke H.; Savic, Rada M.; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J.; Capparelli, Edmund; Jullien, Vincent; Young, Sera L.; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

    2015-01-01

    Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected

  3. COMPARATIVE STUDY OF EFFICACY OF TWO ANTIRETROVIRAL REGIMENTS (ZIDOUVDINE+LAMIVUDINE+NEVIRAPHINE VS STAVUDINE+LAMIVUDINE+NEVIRAPINE IN HIV/AIDS PATIENTS

    Directory of Open Access Journals (Sweden)

    Mopuri Muneer Kanha

    2015-02-01

    Full Text Available BACKGROUND: AIDS, the acquired immunodeficiency syndrome, is the worst disease in the history of medicine due to HIV infection in many sexually active people. This disease is treated with two regimens of drugs in the ART centers at free of cost by the government. AIMS AND OBJECTIVES: To study and compare the efficacy of two antiretroviral regimens (zidovudine +lamivudine+ nevirapine vs ( S tavudine + lamivudine +nevirapine in HIV/AIDS patients. Methods: It is a longitudinal, prospective, observational study, carried at ART centers of siddhartha medical college, Vijayawada, AP and Guntur medical college, Guntur, AP from October 2006 to March 2008. Results: 650 patients were enrolled into study. Out of 650, 325 patients were received Tab.Zidovudine +Tab.Lamivudine+Tab.Nevirapine (Regimen A and 325 patients were received Tab. Stavudine + Tab.Lamivudine + Tab. Nevirapine (Regimen B in fixed drug combination. The study is designed for a Period of 12 months by recording observations at 0 months, 6months and 12months. All the cases enrolled had been studied prospectively at the ART centers and the data entered into the case sheets. The adherence to the ART is assessed by asking the patients to get the empty drug bottles and checking the number of remaining tablets. The chi - square test is applied for all the parameters after 6 months data and after 12 months data with degree of freedom (D f of > 1 = and > P = value as 0.05 (p=0.05 and the level of significance as x 2 >3.84. CONCLUSIONS: Stavudine containing regimen B is having better efficacy than zidovudine containing regimen A

  4. Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique.

    Science.gov (United States)

    Lamorde, Mohammed; Fillekes, Quirine; Sigaloff, Kim; Kityo, Cissy; Buzibye, Allan; Kayiwa, Joshua; Merry, Concepta; Nakatudde-Katumba, Lillian; Burger, David; de Wit, Tobias F Rinke

    2014-09-01

    In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations in plasma and saliva using high performance liquid chromatography (HPLC) methods; and to correlate nevirapine plasma concentrations to HIV treatment outcomes in Ugandan patients. Paired plasma and stimulated saliva samples were obtained from Ugandan, HIV-infected adults on nevirapine-based ART. Nevirapine concentrations were measured using a validated HPLC method and a novel TLC method. Plasma nevirapine concentrations HPLC were considered subtherapeutic. Negative/positive predictive values of different thresholds for subtherapeutic nevirapine concentrations in saliva were determined. Virologic testing and, if applicable, HIV drug resistance testing was performed. Median (interquartile range, IQR) age of 297 patients was 39.1 (32.8-45.2) years. Three hundred saliva and 287 plasma samples were available for analysis. Attempts failed to determine nevirapine saliva concentrations by TLC. Using HPLC, median (IQR) nevirapine concentrations in saliva and plasma were 3.40 (2.59-4.47) mg/L and 6.17 (4.79-7.96) mg/L, respectively. The mean (coefficient of variation,%) nevirapine saliva/plasma ratio was 0.58 (62%). A cut-off value of 1.60 mg/L nevirapine in saliva was associated with a negative/positive predictive value of 0.99/0.72 and a sensitivity/specificity of 87%/98% for predicting subtherapeutic nevirapine plasma concentrations, respectively. Only 5% (15/287) of patients had subtherapeutic nevirapine plasma concentrations, of which 3 patients had viral load results > 400 copies/mL. Patients with nevirapine concentrations in plasma 400 copies/mL). The low-cost TLC technique for monitoring nevirapine in saliva was unsuccessful but monitoring nevirapine saliva and plasma

  5. Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

    Science.gov (United States)

    Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

    2014-11-01

    Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

  6. Fatal nevirapine-induced Stevens- Johnson syndrome with HIV ...

    African Journals Online (AJOL)

    2014-06-01

    Jun 1, 2014 ... of Stevens-Johnson syndrome highlights the dilemmas and complications that may arise when prescribing multiple medications in HIV-associated ... HIV enters the central nervous system early in the course of HIV ... Affected individuals with SJS/TEN are genetically predisposed to developing severe ...

  7. Post-marketing experience with nevirapine extended release (XR) tablets: effectiveness and tolerability in a population-based cohort in British Columbia, Canada.

    Science.gov (United States)

    Lepik, Katherine J; Yip, Benita; McGovern, Rachel A; Ding, Erin; Nohpal, Adriana; Watson, Birgit E; Toy, Junine; Akagi, Linda; Harrigan, P Richard; Moore, David M; Hogg, Robert S; Montaner, Julio S G; Barrios, Rolando

    2015-01-01

    Nevirapine 400 mg extended release tablets (nevirapine-XR) are a once-daily alternative to nevirapine 200 mg immediate release tablets (nevirapine-IR). Study objectives were to describe the effectiveness and tolerability of nevirapine-XR in clinical practice and, for patients who switched from once daily 2×200 mg nevirapine-IR to nevirapine-XR, compare virological suppression and plasma nevirapine concentrations during each treatment period. HIV-1-infected adults entered the study cohort if they initiated nevirapine-XR in British Columbia (BC) Canada between 1 April 2012 and 30 September 2012 and were followed until 30 September 2013. Demographic and clinical variables were abstracted from the BC Centre for Excellence in HIV/AIDS databases. Patients who switched from once daily nevirapine-IR to nevirapine-XR were monitored for 6 months pre- and post-switch with comparison of virological suppression (McNeamer's test) and median random plasma nevirapine concentrations (Wilcoxon-Mann-Whitney test) in each period. The 536 nevirapine-XR-treated patients were 96% male, median (IQR) age 49.9 (44.0-56.9) years. Median follow-up was 15.6 (14.7-16.5) months, with 474/536 (88%) maintaining virological suppression. Emergent drug resistance developed in 5/536 (1%), adverse drug reactions in 17/536 (3%) and, although 31/536 (6%) reported 'whole' tablets in their stools, this was not associated with adverse outcomes. Among the 305 patients who switched from nevirapine-IR to nevirapine-XR, median (IQR) random plasma nevirapine concentration was higher during nevirapine-IR 5,000 (3,690-6,090) ng/ml than nevirapine-XR 3,930 (3,050-5,150) ng/ml (Pmarketing study affirms the effectiveness and tolerability of nevirapine-XR as an alternative to nevirapine-IR in adults.

  8. A retrospective cohort analysis comparing pregnancy rates among HIV-positive women using contraceptives and efavirenz- or nevirapine-based antiretroviral therapy in Kenya

    Science.gov (United States)

    PATEL, Rena C.; ONONO, Maricianah; GANDHI, Monica; BLAT, Cinthia; HAGEY, Jill; SHADE, Starley B.; VITTINGHOFF, Eric; BUKUSI, Elizabeth A.; NEWMANN, Sara J.; COHEN, Craig R.

    2015-01-01

    SUMMARY Background Given recent concerns of efavirenz reducing the efficacy of contraceptive implants, we sought to determine if pregnancy rates differ among HIV-positive women using various contraceptive methods and efavirenz- or nevirapine-based antiretroviral therapy (ART) regimens. Methods We conducted a retrospective cohort analysis of HIV-positive women aged 15–45 years enrolled in HIV care facilities in western Kenya from January 2011 to December 2013. Pregnancy was diagnosed clinically and the primary exposure was a combination of contraceptive method and ART regimen. We used Poisson models, adjusting for repeated measures, as well as demographic, behavioral and clinical factors, to compare pregnancy rates among women on different contraceptive/ART combinations. Findings 24,560 women contributed 37,635 years of follow-up with 3,337 incident pregnancies. Among women using implants, adjusted pregnancy incidence for nevirapine- and efavirenz-based ART users were 1·1 (95% CI 0·72–1·5) and 3·3 (95% CI 1·8–4·8) per 100 women-years (w-y), respectively (adjusted incidence rate ratio (aIRR) 3·0, 95% CI 1·3–4·6). Among women using depomedroxyprogesterone acetate (DMPA), adjusted pregnancy incidence for nevirapine- and efavirenz-based ART users were 4·5 (95% CI 3·7–5·2) and 5·4 (95% CI 4·0–6·8) per 100 w-y, respectively (aIRR 1·2, 95% CI 0·91–1·5). Women using other contraceptive methods, except for intrauterine devices and permanent methods, experienced 3·1–4·1 higher rates of pregnancy than women using implants, with 1·6–2·8 higher rates specifically among women using efavirenz-based ART. Interpretation While HIV-positive women using implants on efavirenz-based ART faced three times higher risk of contraceptive failure than those on nevirapine-based ART, these women still experienced lower contraceptive failure rates than women on all other contraceptive methods, except for intrauterine devices and permanent methods

  9. Risk of nevirapine-associated Stevens-Johnson syndrome among ...

    African Journals Online (AJOL)

    Background. Stevens-Johnson syndrome (SJS) is an acute life-threatening condition often elicited by drugs. The government's indecisiveness in deciding to stop the use of nevirapine (NVP) in HIV-infected pregnant women owing to the increase of SJS among this population group in South Africa prompted this investigation ...

  10. Maternal deaths following nevirapine-based antiretroviral therapy

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    E Bera

    2012-10-01

    Full Text Available We report 2 cases illustrating that it is too simplistic to link nevirapine (NVP toxicity exclusively to individuals with immune preservation. Not enough is known about the mechanism of hepatotoxicity or cutaneous eruption to predict these events. This type of hypersensitivity reaction occurs rarely among HIV-exposed infants taking NVP prophylaxis or antiretroviral therapy (ART-experienced adults with complete plasma viral load suppression. Conversely, HIV-uninfected adults and ART-naive pregnant women appear to be disproportionately affected by the adverse effects of NVP.

  11. Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique

    NARCIS (Netherlands)

    Lamorde, M.; Fillekes, Q.; Sigaloff, K.; Kityo, C.; Buzibye, A.; Kayiwa, J.; Merry, C.; Nakatudde-Katumba, L.; Burger, D.M.; Wit, T.F. de

    2014-01-01

    BACKGROUND: In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations

  12. Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique

    NARCIS (Netherlands)

    Lamorde, Mohammed; Fillekes, Quirine; Sigaloff, Kim; Kityo, Cissy; Buzibye, Allan; Kayiwa, Joshua; Merry, Concepta; Nakatudde-Katumba, Lillian; Burger, David; Rinke de Wit, Tobias F.

    2014-01-01

    In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations in plasma

  13. Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

    Directory of Open Access Journals (Sweden)

    Ashley R. Longstreet

    2013-11-01

    Full Text Available 2-Chloro-3-amino-4-picoline (CAPIC is a strategic building block for the preparation of nevirapine, a widely-prescribed non-nucleosidic reverse transcriptase inhibitor for the treatment of HIV-infected patients. A continuous synthesis to the bromo derivative of a CAPIC intermediate, 2-bromo-4-methylnicotinonitrile, that terminates in a dead-end crystallization is described. The route uses inexpensive, acyclic commodity-based raw materials and has the potential to enable lower cost production of nevirapine as well as other value added structures that contain complex pyridines. The route terminates in a batch crystallization yielding high purity CAPIC. This outcome is expected to facilitate regulatory implementation of the overall process.

  14. HIV-Positive Women Taking Lifelong Antiretroviral Therapy Report Better Adherence Than Women Taking Short-Course Prophylaxis During and After Pregnancy Under PMTCT Program Option A in Lusaka, Zambia.

    Science.gov (United States)

    Hampanda, Karen M; Abuogi, Lisa L; Ahmed, Yusuf

    2017-01-01

    HIV-positive women's adherence to antiretrovirals is critical for prevention of mother-to-child transmission. We aimed to establish if mothers taking triple lifelong antiretroviral therapy report higher adherence compared to mothers taking short-course prophylaxis under Option A in Lusaka, Zambia. In this clinic-based cross-sectional study, we interviewed 320 HIV-positive mothers at a large public health facility in Lusaka in 2014. Participants reported adherence using a visual analog scale. Multiple logistic regression models were used to determine the adjusted odds of adherence by mother's prescribed regimen. Women taking lifelong triple antiretroviral therapy report higher adjusted odds of adherence during pregnancy, postpartum, and to giving the infant prophylaxis compared to women to women taking short-course prophylaxis. Women on lifelong therapy may have better adherence compared to women on short course prophylaxis because they knew their positive status for longer or were symptomatic with HIV-related disease. The lifelong therapy regimen may be easier for women to follow, particularly because they are required to give the infant prophylaxis for a shorter duration of time. Our results indicate that lifelong triple antiretroviral therapy has the potential to promote better drug adherence during and after pregnancy among women living with HIV in sub-Saharan Africa, compared to short-course antiretroviral regimens.

  15. Case Report: Stevens-Johnson syndrome following a single double dosing of nevirapine-containing regimen once in an HIV-infected woman on long-term antiretroviral therapy.

    Science.gov (United States)

    Kakande, Betty; Isaacs, Thuraya; Muloiwa, Rudzani; Dlamini, Sipho; Lehloenya, Rannakoe

    2015-01-01

    A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm (3) in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz). Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir.  We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.

  16. Hepatic adverse events during highly active antiretroviral therapy containing nevirapine: a case report

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    Yamazhan Tansu

    2002-09-01

    Full Text Available Abstract Background Hepatotoxicity is one of the most serious complications of highly active antiretroviral therapy (HAART. The aim of this report is to analyse an HIV infected patient on HAART including nevirapine and taking antidepressive agents, with acute toxic hepatitis. Case presentation A 39 year old patient diagnosed as HIV positive one month ago administered to the clinical ward of the Department of Infectious Diseases and Clinical Microbiology in Ege University Medical School with high fever, malaise, nausea, diarrheae and elevated liver enzymes (ALT 1558 U/L, AST 4288 U/L. He has been using HAART including zidovudine+lamivudine (2 × 1/day and nevirapine (2 × 200 mg/day, following dose escalation for 22 days, sertralin and diazepam for 12 days and lithium for 10 days. The patient was hospitalized. Antiretroviral and antidepressant treatments were stopped. The day after admission, his fever dropped and his symptoms improved. Clinical improvement continued on the following days. The patient was discharged upon his request on the 14th day of hospitalization. The liver function tests returned to normal levels in two weeks following discharge. Conclusion Close monitoring of liver enzymes during the first 12 weeks of nevirapine therapy is critical to prevent life threatening events.

  17. Suboptimal etravirine activity is common during failure of nevirapine-based combination antiretroviral therapy in a cohort infected with non-B subtype HIV-1.

    Science.gov (United States)

    Taiwo, Babafemi; Chaplin, Beth; Penugonda, Sudhir; Meloni, Seema; Akanmu, Sulaimon; Gashau, Wadzani; Idoko, John; Adewole, Isaac; Murphy, Robert; Kanki, Phyllis

    2010-04-01

    The primary objective of this study was to estimate etravirine activity in a cohort of patients infected with non-B subtype HIV-1 and failing nevirapine-based therapy. Genotypic resistance testing was performed if viral load was >OR= 1,000 copies/ml after receiving at least six months of therapy. Suboptimal response to etravirine was predicted by a score >OR= 2.5 on the Tibotec weighting schema, >OR= 4 in the Monogram schema, or classification as high to low-level resistant by a modification of the Stanford HIVdb algorithm (Version 5.1.2). Bivariate and multivariate analyses were conducted to determine the risk factors for suboptimal etravirine activity. The patients (n=91) were receiving nevirapine and lamivudine plus stavudine (57.1%) or zidovudine (42.9%). Median duration of nevirapine exposure was 53 weeks (IQR 46-101 weeks). The most common etravirine resistance associated mutations were Y181C (42.9%), G190A (25.3%), H221Y (19.8%), A98G (18.7%), K101E (16.5%), and V90I (12.1%). Suboptimal etravirine activity was predicted in 47.3 to 56.0%. There were disparities in mutations listed in Tibotec versus Monogram Schemas. Predicted suboptimal activity was not associated with nucleoside reverse transcriptase inhibitor (NRTI) used, gender, pretreatment or current CD4 cell count or viral load, subtype or NRTI mutations. Etravirine has compromised activity in approximately half of the patients failing nevirapine-based first-line treatment in this cohort, which supports guidelines that caution against using it with NRTIs alone in such patients.

  18. Antiretroviral treatment, viral load of mothers & perinatal HIV transmission in Mumbai, India

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    Swati P Ahir

    2013-01-01

    Full Text Available Background & objectives: Mother-to-child transmission (MTCT is the most significant route of HIV transmission in children below the age of 15 yr. In India, perinatal HIV transmission, even after treatment, accounts for 5.4 per cent of HIV cases. The present study was conducted to evaluate the efficacy of anti-retro viral therapy (ART or prophylactic treatment (PT to control maternal viral load in HIV positive women, and its effect on vertical HIV transmission to their infants. Methods: A total of 58 HIV positive women were enrolled at the time of delivery and their plasma samples were obtained within 24 h of delivery for estimation of viral load. Viral load analysis was completed in 38 women. Infants received single dose nevirapine within 2 h of birth and zidovudine for 6 wk. At the end of 18 month follow up, HIV positive or negative status was available in 28 infants. Results: Results revealed undetectable levels of viral load in 58.3 per cent of women with ART compared to 30.7 per cent of women with PT. No women on ART had viral load more than 10,000 copies/ml, whereas seven (26.9%, P=0.07 women receiving PT had this viral load. Median CD4 count of women on PT (483 cells/μl was high compared to the women on ART (289 cells/ μl. At the end of 18 months follow up, only two children were HIV positive, whose mothers were on PT. One had in utero transmission; infection detected within 48 h of delivery, while the other child was infected post partum as HIV was detected at six months follow up. Interpretation & conclusions: Women who received a single dose of nevirapine during delivery had higher levels of viral load than women on ART. Combination drug therapy for pregnant women is now a standard of care in most of the western countries; use of nevirapine monotherapy at the time of delivery in our settings is not effective in controlling viral load. This highlights initiation of ART in pregnant women to control their viral load and thus to inhibit

  19. N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance.

    Directory of Open Access Journals (Sweden)

    Soo-Huey Yap

    2007-12-01

    Full Text Available The catalytically active 66-kDa subunit of the human immunodeficiency virus type 1 (HIV-1 reverse transcriptase (RT consists of DNA polymerase, connection, and ribonuclease H (RNase H domains. Almost all known RT inhibitor resistance mutations identified to date map to the polymerase domain of the enzyme. However, the connection and RNase H domains are not routinely analysed in clinical samples and none of the genotyping assays available for patient management sequence the entire RT coding region. The British Columbia Centre for Excellence in HIV/AIDS (the Centre genotypes clinical isolates up to codon 400 in RT, and our retrospective statistical analyses of the Centre's database have identified an N348I mutation in the RT connection domain in treatment-experienced individuals. The objective of this multidisciplinary study was to establish the in vivo relevance of this mutation and its role in drug resistance.The prevalence of N348I in clinical isolates, the time taken for it to emerge under selective drug pressure, and its association with changes in viral load, specific drug treatment, and known drug resistance mutations was analysed from genotypes, viral loads, and treatment histories from the Centre's database. N348I increased in prevalence from below 1% in 368 treatment-naïve individuals to 12.1% in 1,009 treatment-experienced patients (p = 7.7 x 10(-12. N348I appeared early in therapy and was highly associated with thymidine analogue mutations (TAMs M41L and T215Y/F (p < 0.001, the lamivudine resistance mutations M184V/I (p < 0.001, and non-nucleoside RTI (NNRTI resistance mutations K103N and Y181C/I (p < 0.001. The association with TAMs and NNRTI resistance mutations was consistent with the selection of N348I in patients treated with regimens that included both zidovudine and nevirapine (odds ratio 2.62, 95% confidence interval 1.43-4.81. The appearance of N348I was associated with a significant increase in viral load (p < 0.001, which

  20. Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients.

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    Sanjiv M Baxi

    Full Text Available Effective antiretroviral (ARV therapy depends on adequate drug exposure, yet methods to assess ARV exposure are limited. Concentrations of ARV in hair are the product of steady-state pharmacokinetics factors and longitudinal adherence. We investigated nevirapine (NVP concentrations in hair as a predictor of treatment response in women receiving ARVs. In participants of the Women's Interagency HIV Study, who reported NVP use for >1 month from 2003-2008, NVP concentrations in hair were measured via liquid-chromatography-tandem mass-spectrometry. The outcome was virologic suppression (plasma HIV RNA below assay threshold at the time of hair sampling and the primary predictor was nevirapine concentration categorized into quartiles. We controlled for age, race/ethnicity, pre-treatment HIV RNA, CD4 cell count, and self-reported adherence over the 6-month visit interval (categorized ≤ 74%, 75%-94% or ≥ 95%. We also assessed the relation of NVP concentration with changes in hepatic transaminase levels via multivariate random intercept logistic regression and linear regression analyses. 271 women contributed 1089 person-visits to the analysis (median 3 of semi-annual visits. Viral suppression was least frequent in concentration quartile 1 (86/178 (48.3% and increased in higher quartiles (to 158/204 (77.5% for quartile 4. The odds of viral suppression in the highest concentration quartile were 9.17 times (95% CI 3.2-26, P < 0.0001 those in the lowest. African-American race was associated with lower rates of virologic suppression independent of NVP hair concentration. NVP concentration was not significantly associated with patterns of serum transaminases. Concentration of NVP in hair was a strong independent predictor of virologic suppression in women taking NVP, stronger than self-reported adherence, but did not appear to be strongly predictive of hepatotoxicity.

  1. High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome

    Directory of Open Access Journals (Sweden)

    Sehgal S

    2008-01-01

    Full Text Available In north India the number of paediatric cases with acquired immunodeficiency syndrome (AIDS is on the rise. Most drug combinations used for treatment of AIDS incorporate nevirapine, resistance to which develops very fast if given singly or because of unplanned interruptions. This paper investigates presence of mutations at codon 103 and codon 215 of the HIV pol gene causing resistance to nevirapine and zidovudine (AZT respectively in 25 children with AIDS. Mutations T215Y and K103N were detected by a nested cum amplification refractory mutation system polymerase chain reaction (ARMS PCR and the results were confirmed by direct sequencing in five randomly selected cases. Nineteen patients had received nevirapine containing regimen and six were drug naive. Mutation K103N was observed in 56% (14/25 of the children while mutation T215Y was found in none. Two of the six drug naοve children also showed K103N mutation. Thus, Indian children drug naοve or treated with nevirapine containing regimens show a high rate of mutation conferring resistance to nevirapine which calls for a judicious use of nevirapine both in antenatal and postnatal setting.

  2. Minor drug-resistant HIV type-1 variants in breast milk and plasma of HIV type-1-infected Ugandan women after nevirapine single-dose prophylaxis.

    Science.gov (United States)

    Pilger, Daniel; Hauser, Andrea; Kuecherer, Claudia; Mugenyi, Kizito; Kabasinguzi, Rose; Somogyi, Sybille; Harms, Gundel; Kunz, Andrea

    2011-01-01

    Nevirapine single-dose (NVP-SD) reduces mother-to-child transmission of HIV type-1 (HIV-1), but frequently induces resistance mutations in the HIV-1 genome. Little is known about drug-resistant HIV-1 variants in the breast milk of women who have taken NVP-SD. Blood and breast milk samples of 39 HIV-1-infected Ugandan women were taken 6-12 weeks after NVP-SD intake. Samples were analysed by population sequencing and allele-specific real-time PCR (AS-PCR) with detection limits for NVP-resistant HIV-1 variants (K103N and Y181C) of D n = 5, G n = 2 and C n = 1). A total of 7 (37%) and 10 (53%) women carried NVP-resistant virus in breast milk and plasma, respectively. Overall, 71% (5/7) women with NVP-resistant HIV-1 in breast milk displayed >1 drug-resistant variant. Resistance in breast milk was higher at week 6 (6/13 samples [46%]) compared with week 12 (1/6 samples [17%]). In total, 10 drug-resistant populations harbouring the K103N and/or Y181C mutation were detected in the 19 breast milk samples; 7 (70%) were caused by resistant minorities (< 5% of the total HIV-1 population). In the four women with drug-resistant virus in both plasma and breast milk, the mutation patterns differed between the two compartments. Minor populations of drug-resistant HIV-1 were frequently found in breast milk of Ugandan women after exposure to NVP-SD. Further studies need to explore the role of minor drug-resistant variants in the postnatal transmission of (resistant) HIV-1.

  3. Factors affecting adherence to short-course ARV prophylaxis for preventing mother-to-child transmission of HIV in sub-Saharan Africa: a review and lessons for future elimination.

    Science.gov (United States)

    Colombini, Manuela; Stöckl, Heidi; Watts, Charlotte; Zimmerman, Cathy; Agamasu, Enyonam; Mayhew, Susannah H

    2014-01-01

    Despite the biomedical potential to eliminate vertical HIV transmission, drug adherence to short regimens is often sub-optimal. To inform future programmes, we reviewed evidence on the factors influencing maternal and infant drug adherence to preventing MTCT drug regimens at delivery in sub-Saharan Africa. A literature review yielding 14 studies on adherence to drug regimes among HIV-positive pregnant women and mothers in sub-Saharan Africa was conducted. Rates of maternal adherence to preventive drug regimens at time of delivery varied widely across sites between 35 and 93.5%. Factors most commonly associated with low adherence to antiretroviral therapy (ARV) prophylaxis for preventing MTCT at the health system level include giving birth at home, quality and timing of HIV testing and counselling, and late distribution of nevirapine (NVP). Socio-demographic and demand-side factors include fear of stigma, lack of male involvement, fear of partner's reaction to disclosure, few antenatal (ANC) visits, young age and lack of education. With the implementation of the newly published WHO guidelines recommending triple-drug ARV regimen during pregnancy and breastfeeding for all women with HIV, it is important that women are able to adhere to recommended drug regimens. Service improvements should include clear and timely communication with women about the benefits of combined regimens and greater emphasis on patient confidentiality. Efforts must be made to help women overcome barriers that reduce adherence, such as financial logistical challenges, social stigma and women's fear of violence.

  4. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission.

    Science.gov (United States)

    Kumwenda, Newton I; Hoover, Donald R; Mofenson, Lynne M; Thigpen, Michael C; Kafulafula, George; Li, Qing; Mipando, Linda; Nkanaunena, Kondwani; Mebrahtu, Tsedal; Bulterys, Marc; Fowler, Mary Glenn; Taha, Taha E

    2008-07-10

    Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings. Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth. Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug. Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.) 2008 Massachusetts Medical Society

  5. Lipid-based nutrient supplements do not affect efavirenz but lower plasma nevirapine concentrations in Ethiopian adult HIV patients

    DEFF Research Database (Denmark)

    Abdissa, A; Olsen, Mette Frahm; Yilma, D

    2015-01-01

    OBJECTIVES: Lipid-based nutrient supplements (LNSs) are increasingly used in HIV programmes in resource-limited settings. However, the possible effects of LNSs on the plasma concentrations of antiretroviral drugs have not been assessed. Here, we aimed to assess the effects of LNSs on plasma...... efavirenz and nevirapine trough concentrations in Ethiopian adult HIV-infected patients. METHODS: The effects of LNSs were studied in adults initiating antiretroviral therapy (ART) in a randomized trial. Patients with body mass index (BMI) > 17 kg/m(2) (n = 282) received daily supplementation of an LNS.......9; -0.9 μg/mL; P = 0.01), respectively, compared with the group not receiving supplements. There were no differences between groups with respect to efavirenz plasma concentrations. The CYP2B6 516 G>T polymorphism was associated with a 5 μg/mL higher plasma efavirenz concentration compared with the wild...

  6. The impact of nevirapine- versus protease inhibitor-based regimens on virological markers of HIV-1 persistence during seemingly suppressive ART.

    Science.gov (United States)

    Kiselinova, Maja; Anna, Maria; Malatinkova, Eva; Vervish, Karen; Beloukas, Apostolos; Messiaen, Peter; Bonczkowski, Pawel; Trypsteen, Wim; Callens, Steven; Verhofstede, Chris; De Spiegelaere, Ward; Vandekerckhove, Linos

    2014-01-01

    The source and significance of residual plasma HIV-1 RNA detection during suppressive ART remain controversial. It has been proposed that nevirapine (NVP)-based regimens achieve a greater HIV-1 RNA suppression than regimens containing a protease inhibitor (PI). The aim of this study was to compare the effect of receiving NVP- vs PI-based ART on the virological markers of HIV persistence in peripheral blood. The study population comprised 161 HIV-1 infected patients receiving either NVP-based (n=81) or PI-based (n=80) ART and showing a HIV-1 RNA load stably suppressed ART, with median (IQR) levels of 5 (3-6) and 5 (3-8) copies/mL, respectively. HIV-1 RNA detection was associated with shorter duration of suppressive ART regardless of treatment arm (p=0.007), and lower CD4 nadir (p=0.015). HIV-1 DNA levels were median 282 (120-484) and 213 (87-494) copies/106 PBMCs in the two groups respectively, and were lowest (ART HIV-1 RNA load (p=0.0001). In this comprehensive characterization of patients on long-term suppressive ART, we did not observe evidence for a greater suppressive activity of NVP-based over PI-based therapy on plasma and intracellular markers of virus persistence. Overall excellent correlation was observed between the markers, allowing the identification of a subset of treated patients with low HIV-1 expression as an important cohort for future HIV cure studies.

  7. HIV 991_IN.indd

    African Journals Online (AJOL)

    The median (IQR) infant birth weight was 3.0 (2.6 - 3.5) kg. All received prophylactic nevirapine post exposure. Two of the 15 were clinically unwell at birth, and 14 (86.7%) were breastfed, with 10 ... for the mother and to the baby postpartum,.

  8. Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Ruiz, Lidia; Cozzi-Lepri, Alessandro

    2008-01-01

    OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) wi...

  9. Clinical course of preterm prelabor rupture of membranes in the era of prophylactic antibiotics

    Directory of Open Access Journals (Sweden)

    Phupong Vorapong

    2012-09-01

    Full Text Available Abstract Background Preterm prelabor rupture of membrane (PPROM causes maternal and neonatal complications. Prophylactic antiobiotics were used in the management of PPROM. The objectives of this retrospective study were to compare clinical course and outcome of PPROM managed expectantly with prophylactic antibiotics and antenatal corticosteroids with those without prophylactic antibiotics and antenatal corticosteroids. Results A total of 170 cases of singleton pregnant women with gestational age between 28–34 weeks suffering from PROM during January 1998 to December 2009 were included; 119 cases received prophylactic antibiotics and antenatal corticosteroids while 51 cases did not received prophylactic antibiotics and antenatal corticosteroids. Median latency period in the study group was significantly longer than in the control group (89.8 vs. 24.3 hours, P  Conclusions Latency period of PPROM after using prophylactic antibiotics and antenatal corticosteroids increased while neonatal infectious morbidity was low. But maternal infectious morbidity was not increased. This retrospective study confirms the benefit of prophylactic antibiotics and antenatal corticosteroids in management of PPROM.

  10. Stevens Johnson Syndrome and Toxic Epidermal Necrolysis: Maternal and Foetal Outcomes in Twenty-Two Consecutive Pregnant HIV Infected Women.

    Directory of Open Access Journals (Sweden)

    Lauren Knight

    Full Text Available Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN form a spectrum of a rare and life-threatening cutaneous drug reaction. SJS/TEN in pregnancy poses largely unknown risk factors and outcomes for both the mother and foetus compared to the general population.We conducted a study of consecutive pregnant women admitted to single tertiary referral centre in South Africa with SJS/TEN over a 3 year period. They were all managed by the same medical team using the same protocols. We evaluated their underlying illnesses, offending drugs and the course of pregnancy and outcomes to determine factors influencing maternal and foetal outcomes.We identified twenty-two women who developed SJS/TEN while pregnant, all of them HIV-infected. Their median age was 29 years. The majority 16/22 (73% had SJS, the milder variant of the disease affecting < 10% body surface area. Nevirapine was the offending drug in 21/22 (95% cases. All 22 of the mothers survived with 3/22 (14% developing postpartum sepsis. Pregnancy outcomes were known in 18/22 women and 9/18 (50% babies were delivered by caesarean section. There were 2 foetal deaths at 21 and 31 weeks respectively and both were associated with post-partum sepsis. Postnatal complications occurred in 5 cases, 3 involving the respiratory system and the other two being low birth weight deliveries. Eight placentae and one foetus were sent for histology and none showed macroscopic or microscopic features of SJS/TEN. On follow-up, only 12/20 children were tested for HIV at 6 weeks post-delivery and none of them were HIV-infected. All had received prophylactic ARVs including nevirapine.TEN, the severe form of the disease, was associated with poorer foetal outcomes. SJS/TEN-associated mortality is not increased in HIV-infected pregnant women. Maternal SJS/TEN does not seem to commonly manifest in the foetus.

  11. Prevention of mother-to-child transmission of HIV infection: Views and perceptions about swallowing nevirapine in rural Lilongwe, Malawi

    Directory of Open Access Journals (Sweden)

    Nyirenda Lot J

    2010-06-01

    Full Text Available Abstract Background In 2006 the World Health Organization described the status of prevention of mother to child transmission (PMTCT service implementation as unacceptable, with an urgent need for a renewed public health approach to improve access. For PMTCT to be effective it needs to be accessible, acceptable and affordable; however research in Africa into accessibility, uptake and acceptability of PMTCT services has been predominately urban based and usually focusing on women who deliver in hospitals. The importance of involving other community members to strengthen both PMTCT uptake and adherence, and to support women emotionally, has been advocated. Urban men's and rural traditional birth attendants' (TBAs involvement have improved uptake of HIV testing and of nevirapine. Methods A qualitative study was carried out in a rural district of Malawi's central region to explore the views about and perceptions of PMTCT antiretroviral treatment. Semi-structured interviews and focus group discussions were held with antenatal and postnatal women, fathers, grandmothers, TBAs, community leaders and PMTCT health workers. Results Two broad themes of findings emerged: those that relate to the hospital PMTCT service, and those that relate to the community. Trust in the hospital was strong, but distance, transport costs and perceived harsh, threatening health worker attitudes were barriers to access. Grandmothers were perceived to have influence on the management of labour, unlike fathers, but both were suggested as key people to ensure that babies are brought to the hospital for nevirapine syrup. TBAs were seen as powerful, local, and important community members, but some as uneducated. Conclusion PMTCT was seen as a community issue in which more than the mother alone can be involved. To support access to PMTCT, especially for rural women, there is need for further innovation and implementation research on involving TBAs in some aspects of PMTCT services

  12. The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study

    NARCIS (Netherlands)

    Collaboration, H.-C.; Koopmans †, P.P.; Brouwer, A.M.; Dofferhoff, A.S.M.; Flier, M. van der; Groot, R. de; Hofstede, H.J.M. ter; Keuter, M.; Ven, A.J.A.M. van der; et al.,

    2012-01-01

    OBJECTIVE: To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. DESIGN: Prospective

  13. Participation in two phase II prophylactic HIV vaccine trials in the UK.

    Science.gov (United States)

    Gray, Kimberly; Legg, K; Sharp, A; Mackie, N; Olarinde, F; De Souza, C; Weber, J; Peters, B

    2008-06-02

    There will be a continued imperative to recruit large numbers of healthy volunteers to early phase prophylactic HIV vaccine (PHV) trials. We studied mechanisms associated with participation in two related phase II PHV trials. The most cited reasons for volunteering were altruism and a personal connection to HIV. The most successful recruiting strategies targeted organisations dealing with HIV, health or social issues, or were directed to large audiences through the mass media. However, circulated emails and word of mouth were the most resource-effective approaches. Group discussions and the collection of a pool of potential volunteers were much less effective than one-to-one discussions and immediate screening after recruitment. We utilised our findings to devise key recommendations to assist PHV trial teams who are planning future studies.

  14. Good performance of an immunoassay based method for nevirapine measurements in human breast milk

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Theilgaard, Zahra Persson; Chiduo, Mercy

    2011-01-01

    from HIV-uninfected women. Clinical samples from HIV-infected women receiving a single-dose of nevirapine were analyzed. Results: Precision and accuracy were evaluated with two concentrations of quality control materials analyzed in three replicates on four different days and was......, requires complicated extraction techniques. The ARK method employs an immunoassay technology and requires a small sample volume (40 μL) and no pre-treatment of the samples. Methods: Commercial enzyme and antibody were used and calibration standards and quality controls were prepared from pooled breast milk...

  15. Interventions for preventing late postnatal mother-to-child transmission of HIV.

    Science.gov (United States)

    Horvath, Tara; Madi, Banyana C; Iuppa, Irene M; Kennedy, Gail E; Rutherford, George; Read, Jennifer S

    2009-01-21

    mortality and malnutrition rates during the first two years of life were similar in the two groups. In a trial of early cessation of breastfeeding, HIV-free survival was similar between those children who ceased breastfeeding around four months of age and those who continued breastfeeding. Another trial addressing vitamin supplementation found more cases of HIV infection among children of mothers in the vitamin A arm. Efficacy for other vitamin supplements was not shown. An intervention cohort study evaluated the risk of MTCT according to infant feeding modality, and found increased risks of MTCT among breastfed children who also received solids (hazard ratio = 10.87, p = 0.018) as well as higher 3-month mortality rates (hazard ratio = 2.06) among infants given non- breast milk feedings (instead of exclusive breastfeeding). Three trials evaluated antiretroviral prophylaxis to breastfeeding infants. One trial found that breastfeeding with zidovudine prophylaxis (transmission rate = 9.0%) was not as effective as formula feeding (transmission rate 5.6%) in preventing late postnatal HIV transmission (p = 0.04). Breastfeeding with zidovudine prophylaxis and formula feeding had comparable HIV-free survival rates at 18 months (p = 0.60). Two trials of extended nevirapine prophylaxis demonstrated efficacy. In the first (data combined from trials conducted in three different countries), a six-week course of nevirapine resulted in a lower risk of HIV transmission by six weeks of age (p=0.009), but not at six months of age (p = 0.016). In the second, nevirapine administration until 14 weeks of age (5.2%) or nevirapine with zidovudine until 14 weeks of age (6.4%) resulted in significantly lower risks of MTCT of HIV by 9 months of age than a control regimen of peripartum prophylaxis (10.6%) (p g., diarrheal morbidity if formula is prepared without clean water). If breastfeeding is initiated, two interventions 1). exclusive breastfeeding during the first few months of life; and 2

  16. Renal histoarchitectural changes in nevirapine therapy: possible ...

    African Journals Online (AJOL)

    This study investigates the attenuating effect of kolaviron in nevirapine- therapy on the histological structure ... virapine and vitamin C; Group G was given nevirapine and kolaviron ..... may be better explained using stereological techniques in.

  17. In-home HIV testing and nevirapine dosing by traditional birth attendants in rural Zambia: a feasibility study.

    Science.gov (United States)

    Brennan, Alana T; Thea, Donald M; Semrau, Katherine; Goggin, Caitlin; Scott, Nancy; Pilingana, Portipher; Botha, Belinda; Mazimba, Arthur; Hamomba, Leoda; Seidenberg, Phil

    2014-01-01

    Access to lifesaving prevention of mother-to-child transmission (PMTCT) services is problematic in rural Zambia. The simplest intervention used in Zambia has been 2-dose nevirapine (NVP) administration in the peripartum period, a regimen of 1 NVP tablet to the mother at the onset of labor and 1 dose in the form of syrup to the newborn within 4 to 72 hours after birth. This 2-dose regimen has been shown to reduce MTCT by nearly 50%. We set out to demonstrate that in-home HIV testing and NVP dosing by traditional birth attendants (TBAs) is feasible and acceptable by women in rural Zambia. This was a pilot program using TBAs to perform rapid saliva-based HIV testing and administer single-dose NVP in tablet form to the mother at the onset of labor and syrup to the infant after birth. A total of 280 pregnant women were consented and enrolled into the program, of whom 124 (44.3%) gave birth at home with the assistance of a trained TBA. Of those, 16 (12.9%) were known to be HIV positive, and 101 of the remaining 108 (93.5%) accepted a rapid HIV test. All these women tested HIV negative. In the subset of 16 mothers who were HIV positive, 13 (81.3%) took single-dose NVP administered by a TBA between 1 and 24 hours prior to birth and 100% of exposed newborns (16 of 16) received NVP syrup within 72 hours after birth, 80% of whom were dosed in the first 24 hours of life. With the substantial shortage of human resources in public health care throughout sub-Saharan Africa, it is extremely valuable to utilize lay health care workers to help extended services beyond the level of the facility. Given the high uptake of PMTCT services we believe that TBAs with proper training and support can successfully provide country-approved PMTCT. © 2013 by the American College of Nurse-Midwives.

  18. Population-level effect of potential HSV2 prophylactic vaccines on HIV incidence in sub-Saharan Africa

    Science.gov (United States)

    Freeman, Esther E.; White, Richard G.; Bakker, Roel; Orroth, Kate K.; Weiss, Helen A.; Buvé, Anne; Hayes, Richard J.; Glynn, Judith R.

    2009-01-01

    Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30–40% after 20 years (range 4–66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine. PMID:19071187

  19. Low rate of mother-to-child transmission of HIV-1 after nevirapine intervention in a pilot public health program in Yaoundé, Cameroon.

    Science.gov (United States)

    Ayouba, Ahidjo; Tene, Gilbert; Cunin, Patrick; Foupouapouognigni, Yacouba; Menu, Elisabeth; Kfutwah, Anfumbom; Thonnon, Jocelyn; Scarlatti, Gabriella; Monny-Lobé, Marcel; Eteki, Nicole; Kouanfack, Charles; Tardy, Michèle; Leke, Robert; Nkam, Maurice; Nlend, Anne E; Barré-Sinoussi, Françoise; Martin, Paul M V; Nerrienet, Eric

    2003-11-01

    To determine the percentage of infected children for whom nevirapine (NVP) was used to prevent peripartum mother-to-child transmission (MTCT) of HIV in Yaoundé, Cameroon. The study was a prospective Public Health Pilot Program covering a 3-year period (January 2000-December 2002). Counseled and consenting HIV-1-positive pregnant women were given a single dose of NVP at the onset of labor. Babies were given 2 mg/kg NVP syrup within the first 72 hours of life. NVP-treated children were regularly followed up and examined for HIV-1 infection at 6-8 weeks and 5-6 months through plasma viral load (VL) quantification with the bDNA system. One hundred twenty-three children were diagnosed with perinatal HIV-1 infection at 6-8 weeks and 5-6 months. Thirteen children (10.6% [13/123]; 95% confidence interval, 5.1-16) were infected and presented with high VLs, in general >500,000 copies/mL. Two children had intermediate VLs (between 50 and 3500 copies/mL) at both time points. One hundred seven children (87%) were considered not infected at 6-8 weeks of age. Our results indicate that the HIV-1 MTCT rate 6-8 weeks after NVP administration was not >13% (16/123), thus demonstrating the effectiveness of NVP for lowering the risk of HIV-1 MTCT in real-life settings.

  20. Case Report: Stevens-Johnson syndrome following a single double dosing of nevirapine-containing regimen once in an HIV-infected woman on long-term antiretroviral therapy. [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Betty Kakande

    2015-06-01

    Full Text Available A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm3 in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz.   Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir.  We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.

  1. HIV testing during the neonatal period

    African Journals Online (AJOL)

    2015-04-24

    Apr 24, 2015 ... transmission interventions on 6-week HIV polymerase ... and daily dose nevirapine (NVP) infant prophylaxis (Option B or B+) ... out other antiretrovirals, 32% of intrapartum-infected infants tested HIV DNA PCR negative.

  2. Implementation of a short course of prophylactic antibiotic treatment for prevention of postoperative infections in clean orthopaedic surgeries

    Directory of Open Access Journals (Sweden)

    Purva Mathur

    2013-01-01

    Interpretation & conclusions:There was no significant difference in rates of SSI among the two groups in our study. Cost evaluation revealed that shorter course was less expensive than conventional long course regimen. Implementation of a short course perioperative regimen will go a long way in reducing antimicrobial resistance, cost and adverse reactions to antimicrobials.

  3. A cross-sectional study of the magnitude, barriers, and outcomes of HIV status disclosure among women participating in a perinatal HIV transmission study, "the Nevirapine Repeat Pregnancy study".

    Science.gov (United States)

    Kiweewa, Flavia M; Bakaki, Paul M; McConnell, Michelle S; Musisi, Maria; Namirembe, Constance; Nakayiwa, Frances; Kusasira, Fiona; Nakintu, Dorothy; Mubiru, Michael C; Musoke, Philippa; Fowler, Mary Glenn

    2015-09-29

    HIV status disclosure is a difficult emotional task for HIV-infected persons and may create the opportunity for both social support and rejection. In this study, we evaluated the proportions, patterns, barriers and outcomes of HIV- 1 status disclosure among a group of women in Uganda. An exit interview was conducted one year post-partum for 85 HIV-infected women who participated in a study of HIV-1 transmission rates among NVP-experienced compared with NVP-naïve women in "The Nevirapine Repeat Pregnancy (NVP-RP) Study" at the Makerere University-Johns Hopkins University Research Collaboration, Kampala-Uganda, between June 2004 and June 2006. Of the 85 women interviewed, 99 % had disclosed their HIV status to at least one other person. Disclosure proportions ranged between 1 % to employer(s) and 69 % to a relative other than a parent. Only 38 % of the women had disclosed to their sex partners. Women with an HIV-infected baby were more likely than those with an uninfected baby to disclose to their sex partner, OR 4.9 (95 % CI, 2.0 -11.2), and women were less likely to disclose to a partner if they had previously disclosed to another relative than if they had not, OR 0.19 (95 % CI, 0.14-0.52). The most common reasons for non-disclosure included fear of separation from the partner and subsequent loss of financial support 34 %, and not living with the partner (not having opportunities to disclose) 26 %. While most women (67 %) reported getting social support following disclosure, 22 % reported negative outcomes (neglect, separation from their partners, and loss of financial support). Following disclosure of HIV status, 9 % of women reported that their partner (s) decided to have an HIV test. Results from this study show high overall HIV disclosure proportions and how this disclosure of HIV status can foster social support. However, proportions of disclosure specifically to male sex partners were low, which suggests the need for interventions aimed at increasing male

  4. Effect of Lopinavir and Nevirapine Concentrations on Viral Outcomes in Protease Inhibitor-experienced HIV-infected Children.

    Science.gov (United States)

    Moholisa, Retsilisitsoe R; Schomaker, Michael; Kuhn, Louise; Castel, Sandra; Wiesner, Lubbe; Coovadia, Ashraf; Strehlau, Renate; Patel, Faeezah; Pinillos, Francoise; Abrams, Elaine J; Maartens, Gary; McIlleron, Helen

    2016-12-01

    Adequate exposure to antiretroviral drugs is necessary to achieve and sustain viral suppression. However, the target antiretroviral concentrations associated with long-term viral suppression have not been adequately defined in children. We assessed the relationship between plasma lopinavir or nevirapine concentrations and the risk of subsequent viremia in children initially suppressed on antiretroviral therapy. After an induction phase of antiretroviral treatment, 195 children with viral suppression (viral load ≤400 copies/mL) were randomized to continue a lopinavir/ritonavir-based regimen or to switch to a nevirapine-based regimen (together with lamivudine and stavudine). Viral load and lopinavir or nevirapine concentrations were measured at clinic visits 4, 8, 12, 16, 20, 24, 36, 52, 64 and 76 weeks post randomization. Cox multiple failure event models were used to estimate the effects of drug concentrations on the hazard of viremia (viral load >50 copies/mL) RESULTS:: At randomization, the median (interquartile range) age, CD4 T-Lymphocyte percentage, weight-for-age and weight-for-height z scores were 19 (16-24) months, 29% (23-37), -0.6 (-1.3 to 0.2) and -3.2 (-4.1 to -2.1), respectively. The proportion of children with viral load 51-400 copies/mL at randomization was 43%. The hazard of subsequent viremia during follow-up was increased for lopinavir concentrations <1 versus ≥1 mg/L [adjusted hazard ratio 0.62 (95% confidence interval, 0.40-0.94)] and for children with viral loads 51-400 copies/mL at randomization. Nevirapine concentrations were not significantly associated with subsequent viremia. Plasma lopinavir concentrations predicted viral outcomes in children receiving lopinavir-based antiretroviral therapy. Our findings support a minimum target concentration of ≥1 mg/L of lopinavir to ensure sustained viral suppression.

  5. Short communication: high prevalence of drug resistance in HIV type 1-infected children born in Honduras and Belize 2001 to 2004.

    Science.gov (United States)

    Parham, Leda; de Rivera, Ivette Lorenzana; Murillo, Wendy; Naver, Lars; Largaespada, Natalia; Albert, Jan; Karlsson, Annika C

    2011-10-01

    Antiretroviral therapy has had a great impact on the prevention of mother-to-child transmission (MTCT) of HIV-1. However, development of drug resistance, which could be subsequently transmitted to the child, is a major concern. In Honduras and Belize the prevalence of drug resistance among HIV-1-infected children remains unknown. A total of 95 dried blood spot samples was obtained from HIV-1-infected, untreated children in Honduras and Belize born during 2001 to 2004, when preventive antiretroviral therapy was often suboptimal and consisted of monotherapy with nevirapine or zidovudine. Partial HIV-1 pol gene sequences were successfully obtained from 66 children (Honduras n=55; Belize n=11). Mutations associated with drug resistance were detected in 13% of the Honduran and 27% of the Belizean children. Most of the mutations detected in Honduras (43%) and all mutations detected in Belize were associated with resistance to nonnucleoside reverse transcriptase inhibitors, which was expected from the wide use of nevirapine to prevent MTCT during the study period. In addition, although several mothers reported that they had not received antiretroviral therapy, mutations associated with resistance to nucleoside reverse transcriptase inhibitors and protease inhibitors were found in Honduras. This suggests prior and unreported use of these drugs, or that these women had been infected with resistant virus. The present study demonstrates, for the first time, the presence of drug resistance-associated mutations in HIV-1-infected Honduran and Belizean children.

  6. Therapeutic drug monitoring of nevirapine in resource-limited settings.

    NARCIS (Netherlands)

    L'homme, R.F.A.; Muro, E.P.; Droste, J.A.H.; Wolters, L.R.; Ewijk-Beneken Kolmer, E.W.J. van; Schimana, W.; Burger, D.M.

    2008-01-01

    BACKGROUND: We developed a simple and inexpensive thin-layer chromatography (TLC) assay for semiquantitative detection of saliva concentrations of nevirapine in resource-limited settings. The method was validated in an African target population. METHODS: Paired plasma and saliva nevirapine

  7. Performance of HIV Prevention of Mother-To-Child Transmission Programs in Sub-Saharan Africa: Longitudinal Assessment of 64 Nevirapine-Based Programs Implemented in 25 Countries, 2000-2011.

    Directory of Open Access Journals (Sweden)

    Joël Ladner

    Full Text Available To evaluate the performance and to identify predictive factors of performance in prevention of mother-to-child HIV transmission programs (PMTCT in sub-Saharan African countries.From 2000 to 2011, PMTCT programs included in the Viramune Donation Programme (VDP were prospectively followed. Each institution included in the VDP provided data on program implementation, type of management institution, number of PMTCT sites, key programs outputs (HIV counseling and testing, NVP regimens received by mothers and newborns. Nevirapine Coverage Ratio (NCR, defined as the number of women who should have received nevirapine (observed HIV prevalence x number of women in antenatal care, was used to measure performance. Included programs were followed every six months through progress reports.A total of 64 programs in 25 sub-Saharan African countries were included. The mean program follow-up was 48.0 months (SD = 24.5; 20,084,490 women attended in antenatal clinics were included. The overall mean NCR was 0.52 (SD = 0.25, with an increase from 0.37 to 0.57 between the first and last progress reports (p<.0001; NCR increased by 3.26% per year-program. Between the first and the last report, the number of women counseled and tested increased from 64.3% to 86.0% (p<.0001, the number of women post-counseled from 87.5% to 91.3% (p = 0.08. After mixed linear regression analysis, type of responsible institution, number of women attended in ANC, and program initiation in 2005-2006 were significant predictive factors associated with the NCR. The effect of the time period increased from earlier to later periods.A longitudinal assessment of large PMTCT programs shows that scaling-up of programs was increased in sub-Saharan African countries. The PMTCT coverage increased throughout the study period, especially after 2006. Performance may be better for programs with a small or medium number of women attended in ANC. Identification of factors that predict PMTCT program

  8. Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Saba, J.; Haverkamp, G.; Gray, G.; McIntyre, J.; Mmiro, F.; Ndugwa, C.; Coovadia, H. M.; Moodley, J.; Kilewo, C.; Massawe, A.; Kituuka, P.; Okong, P.; von Briesen, H.; Goudsmit, J.; Biberfeld, G.; Grulich, A.; Weverling, G. J.; Lange, J. M. A.

    2002-01-01

    Background Large reductions in transmission of HIV-1 from mother to child have been achieved in more-developed countries due to the use of antiretrovirals. Short-course regimens, suitable for resource-poor countries, have also been shown to significantly reduce peripartum HIV-1 transmission. We

  9. Rilpivirine exposure in plasma and sanctuary site compartments after switching from nevirapine-containing combined antiretroviral therapy.

    Science.gov (United States)

    Mora-Peris, Borja; Watson, Victoria; Vera, Jaime H; Weston, Rosy; Waldman, Adam D; Kaye, Steve; Khoo, Saye; Mackie, Nicola E; Back, David; Winston, Alan

    2014-06-01

    Pharmacokinetic parameters following modifications to antiretroviral therapy and sanctuary site exposure are often unknown for recently licensed antiretrovirals. We assessed plasma, CSF and seminal plasma (SP) exposure of rilpivirine after switching from nevirapine. HIV-infected male subjects receiving tenofovir/emtricitabine/nevirapine (245/200/400 mg) once daily switched to tenofovir/emtricitabine/rilpivirine (245/200/25 mg) once daily for 60 days when CSF and semen samples were collected. Mean and individual plasma concentrations of nevirapine and rilpivirine were compared with the proposed plasma target concentration for nevirapine (3000 ng/mL) and the protein binding-adjusted EC90 for rilpivirine (12.1 ng/mL). Mean rilpivirine CSF and SP concentrations were calculated and individual values compared with the EC50 and EC90 for wild-type virus (0.27 and 0.66 ng/mL, respectively). Of 13 subjects completing study procedures including CSF examination, 8 provided seminal samples. By day 3, the mean plasma rilpivirine trough concentration was 29.7 ng/mL (95% CI: 23.8-37). No patient presented rilpivirine plasma concentrations under the proposed threshold. The mean rilpivirine concentration in CSF was 0.8 ng/mL (95% CI: 0.7-1.0), representing a CSF : plasma ratio of 1.4%, with concentrations above the EC90 in 85% (11/13) of patients. In SP, the mean rilpivirine concentration was 4.9 ng/mL (95% CI: 3.3-7.2), representing an SP : plasma ratio of 9.5%, with all concentrations above the EC90. Switching from nevirapine- to rilpivirine-containing antiretroviral therapy was safe and well tolerated, with plasma rilpivirine concentrations above the protein binding-adjusted EC90 in all subjects. Rilpivirine concentrations were always above the EC50 in the CSF and the EC90 in SP. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Compatibility studies of nevirapine in physical mixtures with excipients for oral HAART

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, G.G.G. de; Ferraz, H.G. [Department of Pharmacy, Faculty of Pharmaceutical Health, University of Sao Paulo, Sao Paulo 05508-900 (Brazil); Severino, P. [Department of Biotechnological Processes, School of Chemical Engineering, University of Campinas, Campinas 13083-970 (Brazil); Department of Pharmaceutical Technology, Faculty of Health Sciences, Fernando Pessoa University, Porto 4200-150 (Portugal); Souto, E.B., E-mail: eliana@ufp.edu.pt [Department of Pharmaceutical Technology, Faculty of Health Sciences, Fernando Pessoa University, Porto 4200-150 (Portugal); Institute for Biotechnology and Bioengineering, Centre for Genomics and Biotechnology, University of Tras-os-Montes e Alto Douro (IBB-CGB/UTAD), 5001-801 Vila Real (Portugal)

    2013-03-01

    Nevirapine is a hydrophobic non-nucleoside reverse transcriptase inhibitor, used in first line regimens of highly active antiretroviral therapy (HAART). The drug has more than one crystalline form, which may have implications for its behaviour during production and also for its in vivo performance. This study was aimed at exploring the suitability of thermoanalytical methods for the solid-state characterization of commercial crystalline forms of nevirapine. The drug powder was characterized by ultraviolet spectrophotometry, stereoscopy, scanning electron microscopy, wide-angle X-ray diffraction, measurements of density, flowability, solubility and intrinsic dissolution rate (IDR), differential scanning calorimetry, thermogravimetric analysis, and photostability measurements. The results showed that nevirapine has high stability and is not susceptible to degradation under light exposure. The drug showed compatibility with the excipients tested (lactose, microcrystalline cellulose, polyvinylpyrrolidone and polyvinyl acetate copolymer (PVP/PVA), and hydroxypropylmethylcellulose (HPMC)). Nevirapine has low solubility, an acid medium being the most appropriate medium for assessing the release of the drug from dosage forms. However, the data obtained from IDR testing indicate that dissolution is the critical factor for the bioavailability of this drug. - Graphical abstract: Bulk nevirapine powder analysed by scanning electron microscopy and the drug solubility profile in various buffer solutions. The pH values of the media in which the tests were conducted are also presented. Highlights: Black-Right-Pointing-Pointer Nevirapine shows more than one crystalline form, that influence its in vivo and in vitro behaviour. Black-Right-Pointing-Pointer DSC and TGA were used for solid-state characterization of crystalline forms of nevirapine. Black-Right-Pointing-Pointer Nevirapine is compatible with lactose, microcrystalline cellulose, PVP/PVA copolymers and HPMC. Black

  11. Compatibility studies of nevirapine in physical mixtures with excipients for oral HAART

    International Nuclear Information System (INIS)

    Oliveira, G.G.G. de; Ferraz, H.G.; Severino, P.; Souto, E.B.

    2013-01-01

    Nevirapine is a hydrophobic non-nucleoside reverse transcriptase inhibitor, used in first line regimens of highly active antiretroviral therapy (HAART). The drug has more than one crystalline form, which may have implications for its behaviour during production and also for its in vivo performance. This study was aimed at exploring the suitability of thermoanalytical methods for the solid-state characterization of commercial crystalline forms of nevirapine. The drug powder was characterized by ultraviolet spectrophotometry, stereoscopy, scanning electron microscopy, wide-angle X-ray diffraction, measurements of density, flowability, solubility and intrinsic dissolution rate (IDR), differential scanning calorimetry, thermogravimetric analysis, and photostability measurements. The results showed that nevirapine has high stability and is not susceptible to degradation under light exposure. The drug showed compatibility with the excipients tested (lactose, microcrystalline cellulose, polyvinylpyrrolidone and polyvinyl acetate copolymer (PVP/PVA), and hydroxypropylmethylcellulose (HPMC)). Nevirapine has low solubility, an acid medium being the most appropriate medium for assessing the release of the drug from dosage forms. However, the data obtained from IDR testing indicate that dissolution is the critical factor for the bioavailability of this drug. - Graphical abstract: Bulk nevirapine powder analysed by scanning electron microscopy and the drug solubility profile in various buffer solutions. The pH values of the media in which the tests were conducted are also presented. Highlights: ► Nevirapine shows more than one crystalline form, that influence its in vivo and in vitro behaviour. ► DSC and TGA were used for solid-state characterization of crystalline forms of nevirapine. ► Nevirapine is compatible with lactose, microcrystalline cellulose, PVP/PVA copolymers and HPMC. ► The acid form of nevirapine is the most appropriate for assessing release profile from

  12. Reuse of single-dose nevirapine in subsequent pregnancies for the prevention of mother-to-child HIV transmission in Lusaka, Zambia: A cohort study

    Directory of Open Access Journals (Sweden)

    Sinkala Moses

    2008-12-01

    Full Text Available Abstract Background Single-dose nevirapine (SDNVP for the prevention of mother-to-child HIV transmission (PMTCT results in the selection of resistance mutants among HIV-infected mothers. The effects of these mutations on the efficacy of SDNVP use in a subsequent pregnancy are not well understood. Methods We compared risks of perinatal HIV transmission between multiparous women who had previously received a dose of SDNVP (exposed and those that had not (unexposed and who were given SDNVP for the index pregnancy within a PMTCT clinical study. We also compared transmission risks among exposed and unexposed women who had two consecutive pregnancies within the trial. Logistic regression modeling was used to adjust for possible confounders. Results Transmission risks did not differ between 59 SDNVP-exposed and 782 unexposed women in unadjusted analysis or after adjustment for viral load and disease stage (adjusted odds ratio 0.6, 95% confidence interval [CI] 0.2 to 2.0. Among 43 women who had two consecutive pregnancies during the study, transmission risks were 7% (95% CI 1% to 19% at both the first (unexposed and second (exposed delivery. The results were unchanged, if infant death was included as an outcome. Conclusion These data suggest that the efficacy of SDNVP may not be diminished when reused in subsequent pregnancies.

  13. Incidence of nevirapine-associated hepatitis in an antenatal clinic

    African Journals Online (AJOL)

    2008-01-22

    Jan 22, 2008 ... together with a non-nucleoside reverse transcriptase inhibitor, either efavirenz or nevirapine.1 As efavirenz is thought to be a teratogen and is classified as a Food and Drug Administration. (FDA) category D drug, nevirapine is the preferred agent for use in pregnant women, for women planning a pregnancy ...

  14. Efficacy and durability of nevirapine in antiretroviral drug naive patients

    NARCIS (Netherlands)

    Lange, Joep M. A.

    2003-01-01

    Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was first reported in the scientific literature in 1990. Varying doses of nevirapine (NVP) and a number of regimens containing this NNRTI have been studied in antiretroviral (ARV) naive patients. Four key studies have

  15. Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission.

    Science.gov (United States)

    Church, Jessica D; Omer, Saad B; Guay, Laura A; Huang, Wei; Lidstrom, Jessica; Musoke, Philippa; Mmiro, Francis; Jackson, J Brooks; Eshleman, Susan H

    2008-10-01

    Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SD NVP alone for prevention of vertical transmission of human immunodeficiency virus (HIV) through breastfeeding. We analyzed NVP resistance in HIV-infected Ugandan infants who received either SD NVP or extended NVP prophylaxis. We tested plasma HIV by using a genotyping assay (ViroSeq; Celera Diagnostics), a phenotypic resistance assay (PhenoSense; Monogram Biosciences), and sensitive point mutation assay (LigAmp, for K103N, Y181C, and G190A). When infants were 6 weeks old, ViroSeq detected NVP resistance in a higher proportion of infants in the extended NVP arm than in the SD NVP arm (21 of 25 [84%] vs. 12 of 24 [50%]; P = .01). Similar results were obtained with LigAmp and PhenoSense. In both study arms, infants who were HIV infected at birth frequently had NVP resistance detected. In contrast, infants in the extended NVP arm who were HIV infected after birth were more likely to have resistance detected at 6 weeks, compared with infants in the SD NVP arm. The use of extended NVP prophylaxis was also associated with detection of NVP resistance by ViroSeq at 6 months (7 of 7 [100%] infants in the extended NVP arm had resistance detected, compared with 1 of 6 [16.7%] infants in the SD NVP arm; P = .005). The use of extended NVP prophylaxis was associated with increased selection for and persistence of NVP resistance in HIV-infected Ugandan infants.

  16. Durability of Stavudine, Lamivudine and Nevirapine among Advanced HIV-1 Infected Patients with/without Prior Co-administration of Rifampicin: A 144-week Prospective Study

    Directory of Open Access Journals (Sweden)

    Prasithisirikul Wisit

    2008-10-01

    Full Text Available Abstract Background To date, data on the durability of a regimen of stavudine, lamivudine and nevirapine are very limited, particularly from the resource-limited settings. Methods A prospective cohort study was conducted among 140 antiretroviral-naïve patients who were enrolled to initiate d4T, 3TC and NVP between November 2004 and March 2005. The objectives were to determine immunological and virological responses after 144 weeks of antiretroviral therapy. Seventy patients with tuberculosis also received rifampicin during the early period of antiviral treatment (TB group. Results Of all, median (IQR baseline CD4 cell count was 31 (14–79 cells/mm3; median (IQR baseline HIV-1 RNA was 433,500 (169,000–750,000 copies/mL. The average body weight was 55 kilograms. By intention-to-treat analysis at 144 weeks, the overall percentage of patients who achieved plasma HIV-1 RNA P = 0.731. Eight (5.8% patients discontinued d4T due to neuropathy and/or symptomatic lactic acidosis. Conclusion The overall durability and efficacy of antiviral response of d4T, 3TC and NVP are satisfied and they are not different between HIV-1 infected patients with and without co-administration of rifampicin due to tuberculosis. However, stavudine-related adverse effects are concerns. Trial registration ClinicalTrials.gov Identifier NCT00703898

  17. Impact of Nevirapine (NVP) Plasma Concentration on Selection of Resistant Virus in Mothers Who Received Single-Dose NVP To Prevent Perinatal Human Immunodeficiency Virus Type 1 Transmission and Persistence of Resistant Virus in Their Infected Children▿

    OpenAIRE

    Chaix, Marie-Laure; Ekouevi, Didier Koumavi; Peytavin, Gilles; Rouet, François; Tonwe-Gold, Besigin; Viho, Ida; Bequet, Laurence; Amani-Bosse, Clarisse; Menan, Hervé; Leroy, Valériane; Rouzioux, Christine; Dabis, François

    2006-01-01

    Nonnucleoside reverse transcriptase inhibitor resistance following the use of single-dose nevirapine (sdNVP) for the prevention of mother-to-child transmission (PMTCT) remains a concern. In the ANRS-1201/1202 Ditrame study, conducted in Abidjan, Côte d'Ivoire, a short-course regimen of zidovudine was associated with sdNVP for PMTCT. In this study, we estimate the frequency of NVP resistance and its relationship with NVP concentration in mothers. Genotypic resistance analysis was performed on ...

  18. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    Science.gov (United States)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  19. HIV and pregnancy: Maternal and neonatal evolution

    Directory of Open Access Journals (Sweden)

    Diego Cecchini

    2011-10-01

    Full Text Available Data regarding epidemiological aspects, antiretroviral drug safety, and outcomes of HIV-infected pregnant women and their newborns are limited in Argentina. We underwent a retrospective analysis of registries of HIV-infected pregnant women assisted at Helios Salud, Buenos Aires, Argentina (1997-2006. Variables associated with preterm delivery and neonatal complications were analyzed by univariate and logistic regression analyses. A total of 204 mother-child binomium were included. Maternal age (median: 29 years; 32.5% without prior diagnosis of HIV-infection. Baseline median CD4 T-cell count: 417 cell/μl; 98% received antiretroviral drugs during pregnancy [2 nucleoside analogs plus either nevirapine (55% or a protease inhibitor (32%]. Overall incidence of toxicity was 12.5%: rash (8%, anemia (3.5% and hepatotoxicity (1%. Rash was associated with exposure to nevirapine. Eighty one percent and 50% reached HIV-viral loads <1000 and <50 copies/ml at the end of pregnancy, respectively. Twenty six percent had obstetric complications and 16% had preterm delivery. Of the newborns, 1.6% had congenital defects and 9% had neonatal complications. Overall neonatal mortality was 1% and perinatal transmission was 0.7%. Protease inhibitor use and obstetric complications were associated to preterm delivery while obstetric complications were associated with neonatal complications. In our population, hepatotoxicity was low despite frequent use of nevirapine. Protease inhibitor use was associated to preterm delivery. A favorable virological response and a low rate of perinatal transmission was observed, what supports the consensus that antiretroviral therapy benefits during pregnancy outweigh risks of maternal and neonatal adverse events.

  20. Foetal loss and enhanced fertility observed in mice treated with Zidovudine or Nevirapine.

    Science.gov (United States)

    Onwuamah, Chika K; Ezechi, Oliver C; Herbertson, Ebiere C; Audu, Rosemary A; Ujah, Innocent A O; Odeigah, Peter G C

    2014-01-01

    Health concerns for HIV-infected persons on antiretroviral therapy (ART) have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations. A prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females) were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated) mated with the treated males per dose and gave birth to the F1 generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F1 generation were exposed for another 56 days and mated to produce the F2 generation. Foetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F1 generation, births from 10 dams/dose when the 'father-only' was exposed to Zidovudine (10, 100 and 250 mg/kg) was 3, 2 and 1 while it was 7, 1 and 4 respectively when 'both-parents' were exposed. Similarly births from the parental generation first mating when the 'father-only' was exposed to Nevirapine (5, 50 and 150 mg/kg) was 2, 2 and 0 while it was 6, 5 and 9 respectively when 'both-parents' were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F1 mice mated to produce the F2 generation recorded only one birth. The dominant lethal analysis showed foetal loss occurred when the "fathers-only" were treated while fertility was enhanced when "both-parents" were on therapy at the time of mating.

  1. Foetal loss and enhanced fertility observed in mice treated with Zidovudine or Nevirapine.

    Directory of Open Access Journals (Sweden)

    Chika K Onwuamah

    Full Text Available Health concerns for HIV-infected persons on antiretroviral therapy (ART have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations.A prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated mated with the treated males per dose and gave birth to the F1 generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F1 generation were exposed for another 56 days and mated to produce the F2 generation.Foetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F1 generation, births from 10 dams/dose when the 'father-only' was exposed to Zidovudine (10, 100 and 250 mg/kg was 3, 2 and 1 while it was 7, 1 and 4 respectively when 'both-parents' were exposed. Similarly births from the parental generation first mating when the 'father-only' was exposed to Nevirapine (5, 50 and 150 mg/kg was 2, 2 and 0 while it was 6, 5 and 9 respectively when 'both-parents' were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F1 mice mated to produce the F2 generation recorded only one birth.The dominant lethal analysis showed foetal loss occurred when the "fathers-only" were treated while fertility was enhanced when "both-parents" were on therapy at the time of mating.

  2. Prevention of Mother-to-Child Transmission of HIV data ...

    African Journals Online (AJOL)

    2014-08-21

    Aug 21, 2014 ... service delivery in the public health sector of South Africa .... professional nurse in charge of the PMTCT programme at ... 1. antenatal care (ANC) clients pre-test counselled for HIV ..... CD4, Cluster of differentiation; NVP, Nevirapine; PMTCT, prevention of mother-to-child transmission of HIV; DHIS, District.

  3. Sex differences in hepatic and intestinal contributions to nevirapine biotransformation in rats.

    Science.gov (United States)

    Pinheiro, P F; Marinho, A T; Antunes, A M M; Marques, M M; Pereira, S A; Miranda, J P

    2015-05-25

    The understanding of the intestine contribution to drug biotransformation improved significantly in recent years. However, the sources of inter-individual variability in intestinal drug biotransformation, namely sex-differences, are still elusive. Nevirapine (NVP) is an orally taken anti-HIV drug associated with severe idiosyncratic reactions elicited by toxic metabolites, with women at increased risk. As such, NVP is a good model to assess sex-dimorphic metabolism. The aim of this study was to perform a comparative profiling of NVP biotransformation in rat intestine and liver and evaluate whether or not it is organ- and sex-dependent. Therefore, nevirapine-containing solutions were perfused through the intestine, in a specially designed chamber, or incubated with liver slices, from male and female Wistar rats. The levels of NVP and its Phase I metabolites were quantified by HPLC-UV. Liver incubation experiments yielded the metabolites 2-, 3-, 8-, and 12-OH-NVP, being 12-OH-NVP and 2-OH-NVP the major metabolites in males and females, respectively. Inter-sex differences in the metabolic profile were also detected in the intestine perfusion experiments. Herein, the metabolites 3- and 12-OH-NVP were only found in male rats, whereas 2-OH-NVP levels were higher in females, both in extraluminal (pbiotransformation was observed, strengthening the relevance of the intestinal contribution in the biotransformation of orally taken-drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Clinical course of primary HIV infection: consequences for subsequent course of infection

    DEFF Research Database (Denmark)

    Pedersen, C; Lindhardt, B O; Jensen, B L

    1989-01-01

    of symptoms or had mild illness. All six patients who developed AIDS had had longlasting primary illnesses. Three year progression rates to a CD4 lymphocyte count less than 0.5 X 10(9)/l and to recurrence of HIV antigenaemia were significantly higher for those who had longlasting primary illnesses than those......OBJECTIVE--To investigate the impact of the clinical course of the primary HIV infection on the subsequent course of the infection. DESIGN--Prospective documenting of seroconversion, follow up at six month intervals, and analysis of disease progression by life tables. PATIENTS--86 Men in whom...... seroconversion occurred within 12 months. PRIMARY OUTCOME MEASURE--Progression of HIV infection, defined as CD4 lymphocyte count less than 0.5 X 10(9)/l, recurrence of HIV antigenaemia, or progression to Centers for Disease Control group IV. MAIN RESULTS--Median follow up was 670 (range 45-1506) days. An acute...

  5. Protein-mediated antagonism between HIV reverse transcriptase ligands nevirapine and MgATP.

    Science.gov (United States)

    Zheng, Xunhai; Mueller, Geoffrey A; DeRose, Eugene F; London, Robert E

    2013-06-18

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) play a central role in the treatment of AIDS, but their mechanisms of action are incompletely understood. The interaction of the NNRTI nevirapine (NVP) with HIV-1 reverse transcriptase (RT) is characterized by a preference for the open conformation of the fingers/thumb subdomains, and a reported variation of three orders of magnitude between the binding affinity of NVP for RT in the presence or absence of primer/template DNA. To investigate the relationship between conformation and ligand binding, we evaluated the use of methionine NMR probes positioned near the tip of the fingers or thumb subdomains. Such probes would be expected to be sensitive to changes in the local environment depending on the fractions of open and closed RT. Comparisons of the NMR spectra of three conservative mutations, I63M, L74M, and L289M, indicated that M63 showed the greatest shift sensitivity to the addition of NVP. The exchange kinetics of the M63 resonance are fast on the chemical shift timescale, but become slow in the presence of NVP due to the slow binding of RT with the inhibitor. The simplest model consistent with this behavior involves a rapid open/closed equilibrium coupled with a slow interaction of the inhibitor with the open conformation. Studies of RT in the presence of both NVP and MgATP indicate a strong negative cooperativity. Binding of MgATP reduces the fraction of RT bound to NVP, as indicated by the intensity of the NVP-perturbed M230 resonance, and enhances the dissociation rate constant of the NVP, resulting in an increase of the open/closed interconversion rate, so that the M63 resonance moves into the fast/intermediate-exchange regime. Protein-mediated interactions appear to explain most of the affinity variation of NVP for RT. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  6. Anti-HIV drugs nevirapine and efavirenz affect anxiety-related behavior and cognitive performance in mice.

    Science.gov (United States)

    Romão, Pedro R T; Lemos, Joelson C; Moreira, Jeverson; de Chaves, Gisele; Moretti, Morgana; Castro, Adalberto A; Andrade, Vanessa M; Boeck, Carina R; Quevedo, João; Gavioli, Elaine C

    2011-01-01

    Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

  7. The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-Infected Children in Tororo, Uganda

    Science.gov (United States)

    Bartelink, Imke H.; Savic, Rada M.; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J.; Capparelli, Edmund; Jullien, Vincent; Young, Sera L.; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

    2014-01-01

    Background Malnutrition may impact the pharmacokinetics (PK) of antiretroviral medications and virologic responses in HIV-infected children. We therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Methods Sparse dried blood spot (DBS) samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from three resource-rich countries (RRC) were utilized to develop the PK models. Results Concentrations in 330 DBS from 163 Ugandan children aged 0.7–7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5–12 years. Among Ugandan children 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008) respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (Pmalnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessements, to further assess causes of virologic failure in Ugandan children. PMID:25742090

  8. ORIGINAL ARTICLES Nevirapine toxicity- implications for ...

    African Journals Online (AJOL)

    Nevirapine was the first non-nucleoside drug (NNRTI) to be approved by the ... related toxicities in pregnancy were highlighted by a study published in 2004 ..... health, of consumption of scarce financial resources, of concern about doctors ...

  9. Barriers to access prevention of mother-to-child transmission for HIV positive women in a well-resourced setting in Vietnam

    NARCIS (Netherlands)

    Nguyen, T.A.; Oosterhoff, P.P.J.; Yen, P.N.; Wright, P.; Hardon, A.P.

    2008-01-01

    Background: According to Vietnamese policy, HIV-infected women should have access at least to HIV testing and Nevirapine prophylaxis, or where available, to adequate counselling, HIV infection staging, ARV prophylaxis, and infant formula. Many studies in high HIV prevalence settings have reported

  10. Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique.

    Directory of Open Access Journals (Sweden)

    Francisco Antunes

    Full Text Available Single-dose nevirapine (sd-NVP has been the main option for prevention of mother-to-child transmission (PMTCT of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM in the context of PMTCT.To assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique.One hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012 at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA≥ 100 copies/μL (Viroseq. Sequencing was performed with ABI 3100 (Applied Biosystems. Logistic regression modelling was undertaken to identify the factors associated with NVP RAM.Seventy-nine children had their samples genotyped. Their median age was 7.0 (3-12 months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs for PMTCT. ARV RAM were detected in 43 (54.4% of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16 and Y181C (n = 15. NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93-186.34 and with mother's CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02-9.32. In the multivariable analysis the mother's exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33-253.66.We found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers' exposure to PMTCT significantly increased the risk of NVP RAM.

  11. Left ventricular mass in HIV-infected patients.

    Science.gov (United States)

    Olalla, J; Pombo, M; Del Arco, A; de la Torre, J; Urdiales, D; García-Alegría, J

    2013-01-01

    The HIV infection has been associated with an increased incidence of vascular events. Left ventricular mass (LVM) is independently associated with greater overall mortality. Various studies have shown that patients with HIV infection have higher LVM than the uninfected population. We aim to describe the distribution of LVM in an extensive series of patients with HIV infection, and the factors associated with its increase. A cross-sectional study was performed in HIV-infected patients followed in our center from 1 December 2009 to 28 February 2011. A transthoracic echocardiography (TTE) was performed in all patients who gave their consent. Demographic variables, viroimmunological status, cardiovascular risk factors, vascular risk at 10 years (VR10) and history of exposure to antiretroviral drugs were collected. LVM was considered to be the quantitative dependent variable. A univariate analysis was performed, including in the multivariate analysis those variables with P<,05. A TTE was performed in 400 patients, and the LVM was calculated in 388. Mean age was 45 years, 75.5 males. Mean LVM was 39.54g/m(2.7)(95% CI: 38.35-40.73). Age, height, body mass index, VR10, hypertension, dyslipidemia, different medications within the cardiovascular area and having taken nevirapine have been used in the history of the patient were associated to greater LVM. In the multivariate analysis, use of nevirapine in the history of the patient and VR10 remained in the model. VR10 may be associated with greater LVM. The relationship with nevirapine may respond to an indication bias. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  12. A randomized trial comparing initial HAART regimens of nelfinavir/nevirapine and ritonavir/saquinavir in combination with two nucleoside reverse transcriptase inhibitors

    DEFF Research Database (Denmark)

    Kirk, Ole; Lundgren, Jens D; Pedersen, Court

    2003-01-01

    BACKGROUND: A triple-class HAART regimen may be associated with a better virological effect than conventional regimens, but may also lead to toxicity and more profound resistance. METHODS: Randomized, controlled, open-label trial of 233 protease inhibitor- and non-nucleoside reverse transcriptase...... inhibitor-naive HIV-infected patients allocated to a regimen of nelfinavir and nevirapine (1250/200 mg twice daily; n = 118) or ritonavir and saquinavir (400/400 mg twice daily; n = 115), both in combination with two nucleoside reverse transcriptase inhibitors. The primary end-point was HIV RNA ... the long-term consequences of triple class HAART regimens, including the development of broad drug resistance....

  13. Synergistic activity of tenofovir and nevirapine combinations released from polycaprolactone matrices for potential enhanced prevention of HIV infection through the vaginal route.

    Science.gov (United States)

    Dang, Nhung T T; Sivakumaran, Haran; Harrich, David; Shaw, Paul N; Davis-Poynter, Nicholas; Coombes, Allan G A

    2014-10-01

    Polycaprolactone (PCL) matrices were simultaneously loaded with the antiviral agents, tenofovir (TFV) and nevirapine (NVP), in combination to provide synergistic activity in the prevention of HIV transmission through the vaginal route. TFV and NVP were incorporated in PCL matrices at theoretical loadings of 10%TFV-10% NVP, 5%TFV-5%NVP and 5%TFV-10%NVP, measured with respect to the PCL content of the matrices. Actual TFV loadings ranged from 2.1% to 4.2% equating to loading efficiencies of about 41-42%. The actual loadings of NVP were around half those of TFV (1.2-1.9%), resulting in loading efficiencies ranging from 17.2% to 23.5%. Approximately 80% of the initial content of TFV was released from the PCL matrices into simulated vaginal fluid (SVF) over a period of 30 days, which was almost double the cumulative release of NVP (40-45%). The release kinetics of both antivirals over 30 days were found to be described most satisfactorily by the Higuchi model. In vitro assay of release media containing combinations of TFV and NVP released from PCL matrices confirmed a potential synergistic/additive effect of the released antivirals on HIV-1 infection of HeLa cells. These findings indicate that PCL matrices loaded with combinations of TFV and NVP provide an effective strategy for the sustained vaginal delivery of antivirals with synergistic/additive activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. A prospective cohort study comparing the effect of single-dose 2 g metronidazole on Trichomonas vaginalis infection in HIV-seropositive versus HIV-seronegative women.

    Science.gov (United States)

    Balkus, Jennifer E; Richardson, Barbra A; Mochache, Vernon; Chohan, Vrasha; Chan, Jeannie D; Masese, Linnet; Shafi, Juma; Marrazzo, Jeanne; Farquhar, Carey; McClelland, R Scott

    2013-06-01

    This analysis compared the frequency of persistent Trichomonas vaginalis (TV) among HIV-seropositive and HIV-seronegative women. Data were obtained from women enrolled in an open cohort study of sex workers in Kenya. Participants were examined monthly, and those diagnosed as having TV by saline microscopy were treated with single-dose 2 g oral metronidazole. All women on antiretroviral therapy (ART) used nevirapine-based regimens. Generalized estimating equations with a logit link were used to compare the frequency of persistent TV (defined as the presence of motile trichomonads by saline microscopy at the next examination visit within 60 days) by HIV status. Three-hundred sixty participants contributed 570 infections to the analysis (282 HIV-seropositive and 288 HIV-seronegative). There were 42 (15%) persistent infections among HIV-seropositive participants versus 35 (12%) among HIV-seronegative participants (adjusted odds ratio, 1.14; 95% confidence interval [CI], 0.70-1.87). Persistent TV was highest among HIV-seropositive women using ART (21/64 [33%]) compared with HIV-seropositive women not using ART (21/217 [10%]). Concurrent bacterial vaginosis (BV) at TV diagnosis was associated with an increased likelihood of persistent TV (adjusted odds ratio, 1.90; 95% confidence interval, 1.16-3.09). The frequency of persistent TV infection after treatment with single-dose 2 g oral metronidazole was similar by HIV status. Alternative regimens including multiday antibiotic treatment may be necessary to improve cure rates for women using nevirapine-based ART and women with TV and concurrent BV.

  15. The efficacy, pharmacokinetics, safety and cardiovascular risks of switching nevirapine to rilpivirine in HIV-1 patients: the RPV switch study

    NARCIS (Netherlands)

    Rokx, C.; Blonk, M.; Verbon, A.; Burger, D.M.; Rijnders, B.J.

    2014-01-01

    INTRODUCTION: Nevirapine (NVP) induces cytochrome P450 3A4 by which rilpivirine (RPV) is metabolized. Switching NVP to RPV could result in decreased RPV exposure with subsequent virological failure and dyslipidemia because NVP is regarded as the least dyslipidemic, non-nucleoside, reverse

  16. Outcomes for efavirenz versus nevirapine-containing regimens for treatment of HIV-1 infection: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Prinitha Pillay

    Full Text Available There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI efavirenz (EFV and nevirapine (NVP in first-line antiretroviral therapy (ART.We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I(2 statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds.Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73-0.99] I(2 = 0% and observational studies (RR 0.65 [0.59-0.71] I(2 = 54%. EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00-1.08] I(2 = 0% and observational studies (RR 1.06 [1.00-1.12] I(2 = 68%.EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings.

  17. Evaluating the benefits of incorporating traditional birth attendants in HIV prevention of mother to child transmission service delivery in Lilongwe, Malawi.

    Science.gov (United States)

    Hamela, Gloria; Kabondo, Charity; Tembo, Tapiwa; Zimba, Chifundo; Kamanga, Esmie; Mofolo, Innocent; Bulla, Bertha; Sellers, Christopher; Nakanga, R C; Lee, Clara; Martinson, Francis; Hoffman, Irving; van der Horst, Charles; Hosseinipour, Mina C

    2014-03-01

    The objective of our intervention was to examine the benefits of incorporating traditional birth attendants (TBA) in HIV Prevention of Mother to Child Transmission (PMTCT) service delivery. We developed a training curriculum for TBAs related to PMTCT and current TBA roles in Malawi. Fourteen TBAs and seven TBA assistants serving 4 urban health centre catchment areas were assessed, trained and supervised. Focus group discussions with the TBAs were conducted after implementation of the program. From March 2008 to August 2009, a total of 4017 pregnant women visited TBAs, out of which 2133 (53.1%) were directly referred to health facilities and 1,884 (46.9%) women delivered at TBAs and subsequently referred. 168 HIV positive women were identified by TBAs. Of these, 86/168 (51.2%) women received nevirapine and 46/168 (27.4%) HIV exposed infants received nevirapine. The challenges in providing PMTCT services included lack of transportation for referrals and absence of a reporting system to confirm the woman's arrival at the health center. Non-disclosure of HIV status by patients to the TBAs resulted in inability to assist nevirapine uptake. TBAs, when trained and well-supervised, can supplement efforts to provide PMTCT services in communities.

  18. Antioxidant modulation of nevirapine induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Awodele Olufunsho

    2015-03-01

    Full Text Available HIV/AIDS related mortality has been dramatically reduced by the advent of antiretroviral therapy (ART. However, ART presents with associated adverse effects. One of such adverse effects is hepatotoxicity observed with nevirapine (NVP containing ART. Since previous studies showed that NVP hepatotoxicity may be due to oxidative stress via generation of oxidative radicals, this study sought to evaluate the protective effects of antioxidants in alleviating NVP induced hepatotoxicity. Rats were divided into 6 groups with 8 animals per group and received doses of the antioxidants jobelyn (10.7 mg/kg/day, vitamin C (8 mg/kg/day, vitamin E (5 mg/kg/day and/or NVP (6 mg/kg/day for 60 days. The animals were sacrificed on day 61 by cervical dislocation, blood samples were collected for biochemical and hematological examination. The liver of the sacrificed animals was weighed and subjected to histopathological examination. There was a statistically significant (p<0.05 elevation in MDA level observed in the NVP group as compared with control. The results further showed non-significant decreases in the levels of MDA in the NVP plus antioxidant groups, except vitamin C, when compared with the NVP alone group. Vitamin E and Vitamin E plus C treated groups showed significantly (p<0.05 higher levels of SOD, CAT and GSH. The results also showed statistically significantly (p<0.05 lower levels of ALT and AST in the antioxidant treated groups There was an observed significantly (p<0.05 higher level of TP and urea in the antioxidant treated rats. A significantly (p<0.05 higher white blood cell count was observed in the antioxidant groups. Histopathological assessment of the liver extracted from the rats showed no visible pathology across the groups. Observations from this study suggest a potentially positive modulatory effect of antioxidants and may be indicative for the inclusion of antioxidants in nevirapine containing ART.

  19. Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy

    Science.gov (United States)

    Solomon, Ajantha; Ghneim, Khader; Ahlers, Jeffrey; Cameron, Mark J.; Smith, Miranda Z.; Spelman, Tim; McMahon, James; Velayudham, Pushparaj; Brown, Gregor; Roney, Janine; Watson, Jo; Prince, Miles H.; Hoy, Jennifer F.; Chomont, Nicolas; Fromentin, Rémi; Procopio, Francesco A.; Zeidan, Joumana; Palmer, Sarah; Odevall, Lina; Johnstone, Ricky W.; Martin, Ben P.; Sinclair, Elizabeth; Deeks, Steven G.; Hazuda, Daria J.; Cameron, Paul U.; Sékaly, Rafick-Pierre; Lewin, Sharon R.

    2014-01-01

    Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs) are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi) may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART). The primary endpoint was change in cell associated unspliced (CA-US) HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065). Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90%) with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1). CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells. Trial Registration ClinicalTrials.gov NCT01365065 PMID:25393648

  20. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Julian H Elliott

    2014-10-01

    Full Text Available Human immunodeficiency virus (HIV persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART. The primary endpoint was change in cell associated unspliced (CA-US HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065. Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90% with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1. CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells.ClinicalTrials.gov NCT01365065.

  1. The impact of a Wastewater Treatment Works in Southern Gauteng, South Africa on efavirenz and nevirapine discharges into the aquatic environment

    Directory of Open Access Journals (Sweden)

    C. Schoeman

    2017-06-01

    Although an order of magnitude lower nevirapine concentrations displayed the opposite behaviour and gradually increased through the various stages of purification in the WWTP. Minor fluctuations occurred but the concentrations of nevirapine were higher at the effluent (between 92 and 473 ng/L than those entering the WWTP. No nevirapine was detected in the PST sludge. The increase in nevirapine concentrations are likely to be the result of the de-conjugation of the hydroxylated metabolites of nevirapine in the WWTP, its resistance to degradation and the lack of binding of the nevirapine to the PST sludge.

  2. Validation and clinical application of a method to quantify nevirapine in dried blood spots and dried breast-milk spots.

    Science.gov (United States)

    Olagunju, Adeniyi; Amara, Alieu; Waitt, Catriona; Else, Laura; Penchala, Sujan D; Bolaji, Oluseye; Soyinka, Julius; Siccardi, Marco; Back, David; Owen, Andrew; Khoo, Saye

    2015-10-01

    The validation and clinical application of an LC-MS/MS method for the quantification of nevirapine in dried blood spots (DBS) and dried breast-milk spots (DBMS) are presented. DBS and DBMS were prepared from 50 and 30 μL of nevirapine-spiked whole blood and human breast milk, respectively. Chromatographic separation was achieved on a reverse-phase C18 column with 0.1% formic acid in water/acetonitrile using a solvent gradient programme at a flow rate of 400 μL/min, and detection was by a TSQ Quantum Access triple quadrupole mass spectrometer. The clinical application was evaluated in HIV-positive nursing mothers and their breastfed infants. The assay was validated over the concentration range 50-10,000 ng/mL. Accuracy ranged from 93.3% to 113.4% and precision ranged from 1.9% to 12.0%. The mean (percentage coefficient of variation) recovery of nevirapine from DBS and DBMS was ≥ 70.7% (≤ 8.2) and the matrix effect was ≤ 1.04 (≤ 6.1). Nevirapine was stable in DBS and DBMS for ≥ 15 months at room temperature and -80°C. Mean (SD) AUC0-12, Cmax and Cmin in maternal plasma versus breast milk were 57,808 ng · h/mL (24,315) versus 55,817 ng · h/mL (22,368), 6140 ng/mL (2605) versus 5231 ng/mL (2215) and 4334 ng/mL (1880) versus 4342 ng/mL (2245), respectively. The milk-to-plasma concentration ratio over the dosing interval was 0.94 (0.15). Infant plasma concentrations 2 and 8 h after maternal dosing were 580.6 ng/mL (464.7-1607) and 584.1 ng/mL (381.5-1570), respectively. These methods further extend opportunities for conducting clinical pharmacokinetic studies in nursing mother-infant pairs, especially in resource-limited settings. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Good performance of an immunoassay based method for nevirapine measurements in human breast milk

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Persson Theilgaard, Zahra; Chiduo, Mercy

    2011-01-01

    , developed and validated for plasma use. In this study, the ARK NVP-test was evaluated for measurement of nevirapine concentrations in breast milk. High performance liquid chromatography (HPLC) is the method currently used to determine nevirapine in breast milk. This method, however, requires complicated...

  4. Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapy-naive patients infected with HIV-1.

    Directory of Open Access Journals (Sweden)

    Frank van Leth

    2004-10-01

    Full Text Available BACKGROUND: Patients infected with HIV-1 initiating antiretroviral therapy (ART containing a non-nucleoside reverse transcriptase inhibitor (NNRTI show presumably fewer atherogenic lipid changes than those initiating most ARTs containing a protease inhibitor. We analysed whether lipid changes differed between the two most commonly used NNRTIs, nevirapine (NVP and efavirenz (EFV. METHODS AND FINDINGS: Prospective analysis of lipids and lipoproteins was performed in patients enrolled in the NVP and EFV treatment groups of the 2NN study who remained on allocated treatment during 48 wk of follow-up. Patients were allocated to NVP (n = 417, or EFV (n = 289 in combination with stavudine and lamivudine. The primary endpoint was percentage change over 48 wk in high-density lipoprotein cholesterol (HDL-c, total cholesterol (TC, TC:HDL-c ratio, non-HDL-c, low-density lipoprotein cholesterol, and triglycerides. The increase of HDL-c was significantly larger for patients receiving NVP (42.5% than for patients receiving EFV (33.7%; p = 0.036, while the increase in TC was lower (26.9% and 31.1%, respectively; p = 0.073, resulting in a decrease of the TC:HDL-c ratio for patients receiving NVP (-4.1% and an increase for patients receiving EFV (+5.9%; p < 0.001. The increase of non-HDL-c was smaller for patients receiving NVP (24.7% than for patients receiving EFV (33.6%; p = 0.007, as were the increases of triglycerides (20.1% and 49.0%, respectively; p < 0.001 and low-density lipoprotein cholesterol (35.0% and 40.0%, respectively; p = 0.378. These differences remained, or even increased, after adjusting for changes in HIV-1 RNA and CD4+ cell levels, indicating an effect of the drugs on lipids over and above that which may be explained by suppression of HIV-1 infection. The increases in HDL-c were of the same order of magnitude as those seen with the use of the investigational HDL-c-increasing drugs. CONCLUSION: NVP-containing ART shows larger increases in HDL

  5. Easier said than done: World Health Organization recommendations for prevention of mother-to-child transmission of HIV-areas of concern.

    Science.gov (United States)

    Palombi, Leonardo; Nielsen-Saines, Karin; Giuliano, Marina; Marazzi, Maria Cristina

    2011-08-01

    The World Health Organization released recommendations on treatment, prevention, and infant feeding practices within the context of HIV infection based on the "latest scientific evidence" available. The "Rapid Advice" document anticipates the release of official HIV Prevention-of-Mother-to-Child Transmission guidelines. As investigators involved in public health programs providing HIV care in sub-Saharan Africa, we are concerned about the ramifications of specific recommendations, often viewed as dogma by policy makers in this setting. The recommendation that CD4 cell counts be available antenatally so that decisions can be made regarding maternal antiretroviral eligibility is problematic because the ability to measure CD4 cells is nonexistent in many African health centers. As a result, antiretroviral treatment initiation in pregnancy will either be unnecessarily delayed or patients in need of treatment may receive prolonged courses of monotherapy. It is critical that exceptions be made for populations without access to flow cytometry. Another point of concern is that the massive unrestricted use of efavirenz during pregnancy is encouraged. Given that surveillance of pregnancy outcomes is not routinely performed in such settings and in light of the teratogenic potential of efavirenz (contraindicated during the first trimester in developed countries), we are concerned that its indiscriminate use will lead to further problems in vulnerable populations. Another premature recommendation is the use of daily administration of nevirapine to HIV-exposed infants throughout the entire duration of breastfeeding. Results of clinical trials documenting the efficacy of this approach for extended periods of time are not yet available. Single dose nevirapine has been shown to compromise future treatment options in HIV-infected women and infants. In addition, the long-term safety profile of this agent in immune-competent infants has not been established. In summary, although the

  6. Comparing two service delivery models for the prevention of mother-to-child transmission (PMTCT of HIV during transition from single-dose nevirapine to multi-drug antiretroviral regimens

    Directory of Open Access Journals (Sweden)

    Mugwaneza Placidie

    2010-12-01

    Full Text Available Abstract Background Mother-to-child transmission (MTCT of HIV has been eliminated from the developed world with the introduction of multi-drug antiretroviral (md-ARV regimens for the prevention of MTCT (PMTCT; but remains the major cause of HIV infection among sub-Saharan African children. This study compares two service delivery models of PMTCT interventions and documents the lessons learned and the challenges encountered during the transition from single-dose nevirapine (sd-nvp to md-ARV regimens in a resource-limited setting. Methods Program data collected from 32 clinical sites was used to describe trends and compare the performance (uptake of HIV testing, CD4 screening and ARV regimens initiated during pregnancy of sites providing PMTCT as a stand-alone service (stand-alone site versus sites providing PMTCT as well as antiretroviral therapy (ART (full package site. CD4 cell count screening, enrolment into ART services and the initiation of md-ARV regimens during pregnancy, including dual (zidovudine [AZT] +sd-nvp prophylaxis and highly active antiretroviral therapy (HAART were analysed. Results From July 2006 to December 2008, 1,622 pregnant women tested HIV positive (HIV+ during antenatal care (ANC. CD4 cell count screening during pregnancy increased from 60% to 70%, and the initiation of md-ARV regimens increased from 35.5% to 97% during this period. In 2008, women attending ANC at full package sites were 30% more likely to undergo CD4 cell count assessment during pregnancy than women attending stand-alone sites (relative risk (RR = 1.3; 95% confidence interval (CI: 1.1-1.4. Enrolment of HIV+ pregnant women in ART services was almost twice as likely at full package sites than at stand-alone sites (RR = 1.9; 95% CI: 1.5-2.3. However, no significant differences were detected between the two models of care in providing md-ARV (RR = 0.9; 95% CI: 0.9-1.0. Conclusions All sites successfully transitioned from sd-nvp to md-ARV regimens for PMTCT

  7. Virological failure of staggered and simultaneous treatment interruption in HIV patients who began Efavirenz-based regimens after allergic reactions to nevirapine

    Directory of Open Access Journals (Sweden)

    Siripassorn Krittaecho

    2013-01-01

    Full Text Available Abstract Objective The objective of this work was to study the virological outcomes associated with two different types of treatment interruption strategies in patients with allergic reactions to nevirapine (NVP. We compared the virological outcomes of (1 HIV-1-infected patients who discontinued an initial NVP-based regimen because of cutaneous allergic reactions to NVP; different types of interruption strategies were used, and second-line regimen was based on efavirenz (EFV; and (2 HIV-1-infected patients who began an EFV-based regimen as a first-line therapy (controls. Methods This retrospective cohort included patients who began an EFV-based regimen, between January 2002 and December 2008, as either an initial regimen or as a subsequent regimen after resolving a cutaneous allergic reaction against an initial NVP-based regimen. The study ended in March 2010. The primary outcome was virological failure, which was defined as either (a two consecutive plasma HIV-1 RNA levels >400 copies/mL or (b a plasma HIV-1 RNA level >1,000 copies/mL plus any genotypic resistance mutation. Results A total of 559 patients were stratified into three groups: (a Simultaneous Interruption, in which the subjects simultaneously discontinued all the drugs in an NVP-based regimen following an allergic reaction (n=161; (b Staggered Interruption, in which the subjects discontinued NVP treatment while continuing nucleoside reverse transcriptase inhibitor (NRTI backbone therapy for a median of 7 days (n=82; and (c Control, in which the subjects were naïve to antiretroviral therapy (n=316. The overall median follow-up time was 43 months. Incidence of virological failure in Simultaneous Interruption was 12.9 cases per 1,000 person-years, which trended toward being higher than the incidences in Staggered Interruption (5.4 and Control (6.6. However, differences were not statistically significant. Conclusions Among the patients who had an acute allergic reaction to first

  8. Reversible reduction of nevirapine plasma concentrations during rifampicin treatment in patients coinfected with HIV-1 and tuberculosis.

    Science.gov (United States)

    Matteelli, Alberto; Saleri, Nuccia; Villani, Paola; Bonkoungou, Victor; Carvalho, Anna Cristina C; Kouanda, Seni; Sanou, Marie J; Simporé, Jacques; Monno, Laura; Carosi, Giampiero; Regazzi, Mario; Dembele, Mathurin

    2009-09-01

    Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM. HIV-1-infected patients with CD4+ T-lymphocyte count

  9. Lipodystrophy syndrome among HIV infected children on highly ...

    African Journals Online (AJOL)

    Background: It is estimated that about 2.5 million people are living with HIV infection in India. Although antiretroviral drugs have been able to reduce the mortality, these drugs have serious side effects one of which is lipodystrophy syndrome. Most of the drugs used in HAART viz, protease inhibitors, stavudine and nevirapine ...

  10. The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda.

    Science.gov (United States)

    Bartelink, Imke H; Savic, Rada M; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J; Capparelli, Edmund; Jullien, Vincent; Young, Sera L; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

    2015-03-01

    Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Sparse dried blood spot samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from 3 resource-rich countries (RRC) were utilized to develop the PK models. Concentrations in 330 dried blood spot from 163 Ugandan children aged 0.7-7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5-12 years. Among Ugandan children, 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008), respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (PChildren receiving LPV, EFV or NVP had comparable risk of virologic failure. Among children on NVP, low height and weight for age Z scores were associated with reduced risk of virologic failure (P=0.034, P=0.068, respectively). Ugandan children demonstrated lower EFV and LPV and higher NVP exposure compared to children in RRC, perhaps reflecting the consequence of malnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessments, to further assess causes of virologic failure in Ugandan children.

  11. Indian Adolescent Living with HIV-AIDS: Current Clinical Scenario.

    Science.gov (United States)

    Joshi, Kavita S; Bhaware, Bhushan D; Pazare, Amar R

    2017-07-01

    Statistics suggest that, HIV has now largely become the disease of young patients. Hence, the adolescent HIV/AIDS needs to be handled and managed separately from adult HIV. Relatively fewer Indian data exist to characterize the associations in adolescents and young adults infected with HIV disease. The present study explores the current challenges in the management of HIV infected adolescents. The study was aimed at evaluating, relationship between CD4 count and duration of antiretroviral therapy (ART), effects of ART on body mass index and the adverse effects of antiretroviral drugs in adolescent HIV positive patients. This was a cross-sectional study involving 60 HIV positive adolescent patients attending tertiary care Institute KEM Hospital, Parel over duration of one year conducted at Mumbai. Patients on ART between age group 12 to 19 years. ART naïve patients were excluded from the study. 60 adolescent HIV positive patients attended our OPD including 37 males (61.67%) and 23 females (38.33%).The most common mode of transmission was vertical (80%). Education level was: school dropouts - 15%, primary education - 30%, Completed SSC - 31.7%, higher secondary - 23%. Among ADRs were 12 (63.15%) cases of anaemia due to Zidovudine, 4 (21.05%) hepatitis due to Nevirapine, 2 (10.52%) Tenofovir induced AKI and 1 (5.26%) Nevirapine rash. Wilcoxon matched pairs test showed a highly significant increase in the BMI (p ART under government programme has increased the duration of survival of the adolescent population with HIV. Treatment with HAART showed a favourable response with a statistical significant increase in CD4 count. Longer the duration of HAART, higher was the gain in CD4 count. Indian adolescent receiving long term ART, Lipodystrophy is not a troubling issue. Indian adolescent seems to be more tolerance of ART than the other parts of world.

  12. Barriers to uptake of prevention of mother-to-child transmission of HIV services among mothers of vertically infected HIV-seropositive infants in Makurdi, Nigeria

    Directory of Open Access Journals (Sweden)

    Anígilájé EA

    2016-01-01

    Full Text Available Emmanuel Ademola Anígilájé,1 Bem Ruben Ageda,2 Nnamdi Okechukwu Nweke1 1Department of Paediatrics, 2Department of Obstetrics and Gynaecology, Federal Medical Centre, Makurdi, Nigeria Background: Perinatal transmission of human immunodeficiency virus (HIV continues in Nigeria because of the poor use of prevention of mother-to-child transmission of HIV (PMTCT services. This study reports on the barriers preventing mothers of vertically infected HIV-seropositive infants to use the PMTCT services at the Federal Medical Centre, Makurdi, Nigeria.Methods: This is a descriptive study conducted between January and April, 2014. A quantitative survey was applied to detect barriers along the PMTCT services cascade among 52 mothers of vertically infected HIV-seropositive infants. This includes 22 women who attended antenatal care at the Federal Medical Centre (designated as Group A mothers and 30 women who did not receive any form of PMTCT service (Group B mothers. The study was supplemented with a focused group discussion involving 12 discussants from the two groups.Results: In the quantitative assessment: among the Group A mothers, falling asleep was the most common reason (n=22, 100% for missing therapeutic/prophylactic antiretroviral medicine; financial constraint (n=22, 100% was the most common reason for antenatal care visit defaults; and a lot of the mothers (n=11, 50.0% did not give nevirapine to their newborns because they delivered at home. Among Group B mothers, unawareness of HIV-seropositive status was the most common reason (n=28, 93.3% given for not accessing PMTCT services. In the qualitative study: noninvolvement of male partners, stigma and discrimination experienced by HIV-seropositive mothers, financial constraints in couples, involvement of traditional birth attendants in antenatal care and delivery of HIV-infected women, unawareness of HIV-seropositive status by pregnant women, poor health system, and the lack of funding for PMTCT

  13. Assessing the effect of an online HIV/AIDS course on 1st-year ...

    African Journals Online (AJOL)

    Background. More international HIV/AIDS intervention initiatives targeting young adults are needed to help reach targets set by the Joint United Nations Programme on HIV and AIDS (UNAIDS). Objectives. To determine the effect of an online HIV/AIDS course on 1st-year pharmacy students' knowledge of HIV prevention and ...

  14. [Effects of prophylactic chemotherapy on outcomes and prognosis of patients older than 40 years with invasive mole].

    Science.gov (United States)

    Jiang, S Y; Li, L; Zhao, J; Xiang, Y; Wan, X R; Feng, F Z; Ren, T; Yang, J J

    2017-06-25

    Objective: To discuss the effects of prophylactic chemotherapy on the outcomes and prognosis of invasive mole patients. Methods: One hundred and fifteen invasive mole (IM) patients older than 40 years were registered in Peking Union Medical Collage Hospital.Eleven of them were treated with prophylactic chemotherapy before diagnosed as IM prophylactic chemotherapy group, while the other 104 cases received therapeutic chemotherapy after diagnosed as IM (non-prophylactic chemotherapy group). The general clinical data (including age, clinical stage, risk factor score), treatment, outcomes and relapse of patients were retrospectively compared between two groups. Results: (1) The age of prophylactic chemotherapy group and non-prophylactic chemotherapy group were (47±5) versus (46±4) years old. Ratio of clinical stageⅠ-Ⅱ were 3/11 versus 29.8% (31/104), clinical stage Ⅲ-Ⅳ were 8/11 versus 70.2% (73/104). Ratio of risk factor score 0-6 were 11/11 versus 84.6% (88/104), risk factor score >6 were 0 versus 15.4% (16/104). There were no significant statistical differences between two groups in age, clinical stage or risk factor score (all P> 0.05). (2) Treatment: the total chemotherapy courses between prophylactic chemotherapy group and non-prophylactic chemotherapy group (median 7 versus 5) were significantly different ( Z= 3.071, P= 0.002). There were no significant statistical differences between two groups in the chemotherapy courses until negative conversion of β-hCG, consolidation chemotherapy courses, total therapeutic chemotherapy courses or ratio of hysterectomy (all P> 0.05). (3) Outcomes and relapse: between the prophylactic chemotherapy group and the non-prophylactic chemotherapy group, the complete remission rate were 11/11 versus 98.1%(102/104), the relapse rate were 0 versus 1.0%(1/102). There were no significant difference between the two groups in outcomes or relapse rate ( P> 0.05). Conclusions: Prophylactic chemotherapy does not substantially

  15. Short-course versus long-course chemoradiation in rectal cancer--time to change strategies?

    Science.gov (United States)

    Palta, Manisha; Willett, Christopher G; Czito, Brian G

    2014-09-01

    There is significant debate regarding the optimal neoadjuvant regimen for resectable rectal cancer patients. Short-course radiotherapy, a standard approach throughout most of northern Europe, is generally defined as 25 Gy in 5 fractions over the course of 1 week without the concurrent administration of chemotherapy. Long-course radiotherapy is typically defined as 45 to 50.4 Gy in 25-28 fractions with the administration of concurrent 5-fluoropyrimidine-based chemotherapy and is the standard approach in other parts of Europe and the United States. At present, two randomized trials have compared outcomes for short course radiotherapy with long-course chemoradiation showing no difference in respective study endpoints. Late toxicity data are lacking given limited follow-up. Although the ideal neoadjuvant regimen is controversial, our current bias is long-course chemoradiation to treat patients with locally advanced, resectable rectal cancer.

  16. EFFECT OF SHORT-TERM ART INTERRUPTION ON LEVELS OF INTEGRATED HIV DNA.

    Science.gov (United States)

    Strongin, Zachary; Sharaf, Radwa; VanBelzen, D Jake; Jacobson, Jeffrey M; Connick, Elizabeth; Volberding, Paul; Skiest, Daniel J; Gandhi, Rajesh T; Kuritzkes, Daniel R; O'Doherty, Una; Li, Jonathan Z

    2018-03-28

    Analytic treatment interruption (ATI) studies are required to evaluate strategies aimed at achieving ART-free HIV remission, but the impact of ATI on the viral reservoir remains unclear. We validated a DNA size selection-based assay for measuring levels of integrated HIV DNA and applied it to assess the effects of short-term ATI on the HIV reservoir. Samples from participants from four AIDS Clinical Trials Group (ACTG) ATI studies were assayed for integrated HIV DNA levels. Cryopreserved PBMCs were obtained for 12 participants with available samples pre-ATI and approximately 6 months after ART resumption. Four participants also had samples available during the ATI. The median duration of ATI was 12 weeks. Validation of the HIV Integrated DNA size-Exclusion (HIDE) assay was performed using samples spiked with unintegrated HIV DNA, HIV-infected cell lines, and participant PBMCs. The HIDE assay eliminated 99% of unintegrated HIV DNA species and strongly correlated with the established Alu- gag assay. For the majority of individuals, integrated DNA levels increased during ATI and subsequently declined upon ART resumption. There was no significant difference in levels of integrated HIV DNA between the pre- and post-ATI time points, with the median ratio of post:pre-ATI HIV DNA levels of 0.95. Using a new integrated HIV DNA assay, we found minimal change in the levels of integrated HIV DNA in participants who underwent an ATI followed by 6 months of ART. This suggests that short-term ATI can be conducted without a significant impact on levels of integrated proviral DNA in the peripheral blood. IMPORTANCE Interventions aimed at achieving sustained antiretroviral therapy (ART)-free HIV remission require treatment interruption trials to assess their efficacy. However, these trials are accompanied by safety concerns related to the expansion of the viral reservoir. We validated an assay that uses an automated DNA size-selection platform for quantifying levels of integrated

  17. Design and expression of a short peptide as an HIV detection probe

    Energy Technology Data Exchange (ETDEWEB)

    Lines, Jamie A.; Yu, Zhiqiang; Dedkova, Larisa M.; Chen, Shengxi, E-mail: shengxi.chen.1@asu.edu

    2014-01-03

    Highlights: •We designed a short fusion peptide (FP-50) for in vivo expression. •This peptide is a very promising component for detection of gp120 protein. •The detectable level is about 20–200 times lower than previously published methods. •It is a novel probe to detect HIV-1 gp120 during early stages of HIV infection. -- Abstract: To explore a low-cost novel probe for HIV detection, we designed and prepared a 50-amino acid-length short fusion peptide (FP-50) via Escherichia coli in vivo expression. It was employed as a novel probe to detect HIV-1 gp120 protein. The detectable level of gp120 protein using the FP-50 peptide was approximately 20–200 times lower than previously published methods that used a pair of monoclonal antibodies. Thus, this short peptide is a very promising component for detection of gp120 protein during early stages of HIV infection.

  18. ULTRASOUND DIAGNOSIS OF VENOUSTHROMBOSIS IN THE COURSE OF PROPHYLACTIC DRUG THERAPY IN THE ACUTE PHASE OF TRAUMA

    Directory of Open Access Journals (Sweden)

    L. O. Mezhebitskaya

    2015-01-01

    Full Text Available  INTRODUCTION. High risk of venous thrombosis in patients with multisystem trauma is associated with a number of precipitating factors, such as direct damage to vessels, prolonged immobilization, major changes in the hemostatic system, as well as possible surgical intervention.THE PURPOSE OF THE STUDY. Analysis of the incidence, echosemiotics, and evolutionof venous thrombosis in the course of various prophylactic drug therapies in patients with polytrauma.METHODS. The results of leg veins ultrasonography in 610 patients with various prophylactic drugtherapies have been analyzed over time. Antiplatelet agentswere received by 314 patients of the first group, low molecular weight heparins — 186 patients of the second group, oral anticoagulants — 110 patients of the third group. THE RESulTS Evolved thromboses varied in frequency (52.5% in the first group, 15.6% in the 2nd group and 10% in the 3rd group, prevalence, nature of the proximal border, with an increase in the proportion of nonocclusive lesions in the 2nd and 3rd groups, as well as in start time and degree of recanalization.CONCLUSION. Low molecular weight heparins and oral anticoagulants reduce the risk of venous thrombosis by 3.3 and 5 times respectively, compared to the group of patients who did not receive anticoagulants in the early posttraumatic period; recanalization begins 1−2 weeks earlier with more effective restoration of the lumen. As the number of thromboses in the course of modern anticoagulants decreases, the proportion of non-occlusive thromboses including the floating onesgrows, requiring ultrasoundobservation. 

  19. Introduction to nanotechnology: a short course for high school students

    Science.gov (United States)

    Markin, Alexey V.

    2016-04-01

    This report devoted to presenting results of development and implementation of a short course (4 hours) entitled "Introduction to Nanotechnology" that was specially designed for familiarizing high school students with nanomaterials and nanotechnology. The course contains introduction to nanotechnology, essential definitions, short overview of history, descriptions for various examples of nanomaterials and their classifications, performing demonstration experiments. All these parts of the course are briefly analyzed from pedagogical effectiveness point of view. Finally, results of course testing, problems and perspectives of nano-oriented education at high school are also discussed shortly.

  20. An increase in rates of obstetric haemorrhage in a setting of high HIV seroprevalence

    Directory of Open Access Journals (Sweden)

    E Shabalala

    2017-07-01

    Full Text Available Background. Obstetric haemorrhage (OH is the leading cause of maternal mortality worldwide, although, indirectly, HIV is also a leading cause of maternal mortality in some settings with a high HIV seroprevalence. Objective. To determine the possible association between increasing rates of OH and HIV or its treatment. Methods. We conducted a retrospective chart review of women with OH at King Edward VIII Hospital, Durban, South Africa, over a 3-year period (2009 - 2011, during which the drug regimen for the prevention of mother-to-child transmission was evolving from single-dose nevirapine to antenatal zidovudine combined with intrapartum nevirapine (also referred to as dual therapy, and finally to a combination or highly active antiretroviral therapy (cART or HAART. Cases of OH (including abruptio placentae, placenta praevia, unspecified antepartum haemorrhage (APH, and postpartum haemorrhage (PPH were identified from maternity delivery records, and the relevant data extracted. Results. We analysed the records of 448 women diagnosed with OH. Even though the incidence of OH was low, the study found an increasing number of cases during the 3-year period. PPH – not APH – was associated with HIV seropositivity (odds ratio 1.84, 95% confi­dence interval 1.14 - 2.95. cART was not associated with an increased risk of haemorrhage. Conclusion. HIV was associated with a high risk of PPH, and its possible association with HIV treatment needs further research.

  1. Prophylactic treatment uptake and compliance with recommended follow up among HIV exposed infants: a retrospective study in Addis Ababa, Ethiopia

    Directory of Open Access Journals (Sweden)

    Shargie Mulatu

    2011-12-01

    Full Text Available Abstract Background Children are being infected by HIV/AIDS mainly through mother-to-child transmission. In Ethiopia currently more than 135,000 children are living with HIV/AIDS. The aim of this study was to describe the pattern of ARV uptake after birth, co-trimoxazole prophylaxis and follow up compliance, and to examine which factors are associated with the intervention outcome. Methods A retrospective quantitative study design was used for data collection through two hospitals. All infants who were delivered by HIV infected mothers between October 2008 and August 2009 were included and information regarding treatment adherence during their first 6 months of age was collected. Findings 118 HIV exposed infant-mother pairs were included in the study. 107 (90.7% infants received ARV prophylaxis at birth. Sixty six (56% of the infants were found to be adherent to co-trimoxazole prophylactic treatment. The majority (n = 110(93.2% of infants were tested HIV negative with DNA/PCR HIV test at the age of sixth weeks. Infants who took ARV prophylaxis at birth were found to be more likely to adhere with co-trimoxazole treatment: [OR = 9.43(95% CI: 1.22, 72.9]. Similarly, infants whose mothers had been enrolled for HIV/ART care in the same facility [OR = 14(95% CI: 2.6, 75.4], and children whose fathers were tested and known to be HIV positive [OR = 3.0(95% CI: 1.0, 9.0] were more likely to adhere than their counterparts. Infants feeding practice was also significantly associated with adherence χ2 -test, p Conclusion The proportion of ARV uptake at birth among HIV exposed infants were found to be high compared to other similar settings. Mother-infant pair enrolment in the same facility and the infant's father being tested and knew their HIV result were major predictors of infants adhering to treatment and follow up. However, large numbers of infants were lost to follow up.

  2. Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children

    NARCIS (Netherlands)

    Bienczak, A.; Cook, A.; Wiesner, L.; Mulenga, V.; Kityo, C.; Kekitiinwa, A.; Walker, A.S.; Owen, A.; Gibb, D.M.; Burger, D.M.; McIlleron, H.; Denti, P.

    2017-01-01

    OBJECTIVES: To characterize the effects of CYP2B6 polymorphisms, diurnal variation and demographic factors on nevirapine pharmacokinetics in African children. METHODS: Non-linear mixed-effects modelling conducted in NONMEM 7.3 described nevirapine plasma concentration-time data from 414 children

  3. Sensitivity of the ViroSeq HIV-1 Genotyping System for Detection of the K103N Resistance Mutation in HIV-1 Subtypes A, C, and D

    Science.gov (United States)

    Church, Jessica D.; Jones, Dana; Flys, Tamara; Hoover, Donald; Marlowe, Natalia; Chen, Shu; Shi, Chanjuan; Eshleman, James R.; Guay, Laura A.; Jackson, J. Brooks; Kumwenda, Newton; Taha, Taha E.; Eshleman, Susan H.

    2006-01-01

    The US Food and Drug Administration-cleared ViroSeq HIV-1 Genotyping System (ViroSeq) and other population sequencing-based human immunodeficiency virus type 1 (HIV-1) genotyping methods detect antiretroviral drug resistance mutations present in the major viral population of a test sample. These assays also detect some mutations in viral variants that are present as mixtures. We compared detection of the K103N nevirapine resistance mutation using ViroSeq and a sensitive, quantitative point mutation assay, LigAmp. The LigAmp assay measured the percentage of K103N-containing variants in the viral population (percentage of K103N). We analyzed 305 samples with HIV-1 subtypes A, C, and D collected from African women after nevirapine administration. ViroSeq detected K103N in 100% of samples with >20% K103N, 77.8% of samples with 10 to 20% K103N, 71.4% of samples with 5 to 10% K103N, and 16.9% of samples with 1 to 5% K103N. The sensitivity of ViroSeq for detection of K103N was similar for subtypes A, C, and D. These data indicate that the ViroSeq system reliably detects the K103N mutation at levels above 20% and frequently detects the mutation at lower levels. Further studies are needed to compare the sensitivity of different assays for detection of HIV-1 drug resistance mutations and to determine the clinical relevance of HIV-1 minority variants. PMID:16931582

  4. Validation of Six Short and Ultra-short Screening Instruments for Depression for People Living with HIV in Ontario

    DEFF Research Database (Denmark)

    Choi, Stephanie KY; Boyle, Eleanor; Burchell, Ann

    2015-01-01

    Objective Major depression affects up to half of people living with HIV. However, among HIV-positive patients, depression goes unrecognized 60–70% of the time in non-psychiatric settings. We sought to evaluate three screening instruments and their short forms to facilitate the recognition...... acceptance. This could lead to clinical benefits in fast-paced speciality HIV care settings and better management of depression in HIV-positive patients....

  5. CERN Technical Training 2005: New Short Course (SC) Sessions on Office Software - July 2005

    CERN Multimedia

    Davide Vitè

    2005-01-01

    The following new course sessions are currently scheduled in the framework of the CERN Technical Training Programme 2005, within the Office Software curriculum: OUTLOOK 2003 (Short Course I) - E-mail : 6.7.2005 (morning) OUTLOOK 2003 (Short Course II) - Calendar, Tasks and Notes : 7.7.2005 (morning) OUTLOOK 2003 (Short Course III) - Meetings and Delegation : 8.7.2005 (morning) WORD 2003 (Short Course I) - HowTo... Work with repetitive tasks: 4.7.2005 (afternoon) WORD 2003 (Short Course II) - HowTo... Mail merge : 5.7.2005 (afternoon) WORD 2003 (Short Course III) - HowTo... Work with long documents : 6.7.2005 (afternoon) EXCEL 2003 (Short Course I) - HowTo... Work with formulae : 7.7.2005 (afternoon) EXCEL 2003 (Short Course II) - HowTo... Format your worksheet for printing : 8.7.2005 (afternoon) All the above sessions are organised in the new format of Short Courses (SC): 3 hour sessions (9h30-12h30 or 14h30-17h30), at a nominal cost of 75.- CHF per person per course. Any course can be followed independe...

  6. Paying to waste lives: the affordability of reducing mother-to-child transmission of HIV in South Africa.

    Science.gov (United States)

    Skordis, Jolene; Nattrass, Nicoli

    2002-05-01

    It is estimated that each HIV-positive child in South Africa costs the government more in terms of health and welfare expenses than it does to reduce mother-to-child transmission (MTCT) of HIV through the use of antiretroviral regimens (where the mother continues to breast-feed). Programmes to reduce MTCT of HIV/AIDS are, thus, clearly affordable. Using Nevirapine (according to the HIVNET 012 Protocol) saves more lives and [corrected] is more cost-effective than using Zidovudine (CDC 2 weeks regime).

  7. Genome-wide association scan in HIV-1-infected individuals identifying variants influencing disease course.

    Directory of Open Access Journals (Sweden)

    Daniëlle van Manen

    Full Text Available BACKGROUND: AIDS develops typically after 7-11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (15 years. To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. METHODS: The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints. RESULTS: Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression. CONCLUSIONS: Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection.

  8. Genome-Wide Association Scan in HIV-1-Infected Individuals Identifying Variants Influencing Disease Course

    Science.gov (United States)

    van Manen, Daniëlle; Delaneau, Olivier; Kootstra, Neeltje A.; Boeser-Nunnink, Brigitte D.; Limou, Sophie; Bol, Sebastiaan M.; Burger, Judith A.; Zwinderman, Aeilko H.; Moerland, Perry D.; van 't Slot, Ruben; Zagury, Jean-François; van 't Wout, Angélique B.; Schuitemaker, Hanneke

    2011-01-01

    Background AIDS develops typically after 7–11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (15 years). To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS) in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Methods The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints. Results Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression. Conclusions Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection. PMID:21811574

  9. Challenges in the concurrent management of malaria and HIV in pregnancy in sub-Saharan Africa.

    Science.gov (United States)

    Brentlinger, Paula E; Behrens, Christopher B; Micek, Mark A

    2006-02-01

    Approximately one million pregnancies are complicated by both malaria and HIV infection in sub-Saharan Africa annually. Both infections have been associated with maternal and infant morbidity and mortality. Intermittent preventive treatment, usually with sulfadoxine-pyrimethamine, has been shown to prevent pregnancy-related malaria and its complications. Several different regimens of antiretroviral therapy are now available to prevent mother-to-child transmission of HIV and/or progression of maternal HIV infection during pregnancy. However, no published studies have yet shown whether standard intermittent preventive treatment and antiretroviral regimens are medically and operationally compatible in pregnancy. We reviewed existing policies regarding prevention and treatment of HIV and malaria in pregnancy, as well as published literature on adverse effects of antiretrovirals and antimalarials commonly used in pregnancy in developing countries, and found that concurrent prescription of sulfadoxine-pyrimethamine, co-trimoxazole (trimethoprim-sulfamethoxazole), and antiretroviral agents including nevirapine and zidovudine per existing protocols for prevention of malaria and vertical HIV transmission may result in adverse drug interactions or overlapping, diagnostically challenging drug toxicities. Insecticide-treated bednets should be provided for HIV-infected pregnant women at risk for malaria. Sulfadoxine-pyrimethamine should be prescribed cautiously in women concurrently receiving daily nevirapine and/or zidovudine, and should be avoided in women on daily co-trimoxazole. Further research is urgently needed to define safe and effective protocols for concurrent management of HIV and malaria in pregnancy, and to define appropriate interventions for different populations subject to differing levels of malaria transmission and antimalarial drug resistance.

  10. Subtask 4.2 - Coal Gasification Short Course

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Galbreath

    2009-06-30

    Major utilities, independent power producers, and petroleum and chemical companies are intent on developing a fleet of gasification plants primarily because of high natural gas prices and the implementation of state carbon standards, with federal standards looming. Currently, many projects are being proposed to utilize gasification technologies to produce a synthesis gas or fuel gas stream for the production of hydrogen, liquid fuels, chemicals, and electricity. Financing these projects is challenging because of the complexity, diverse nature of gasification technologies, and the risk associated with certain applications of the technology. The Energy & Environmental Research Center has developed a gasification short course that is designed to provide technical personnel with a broad understanding of gasification technologies and issues, thus mitigating the real or perceived risk associated with the technology. Based on a review of research literature, tutorial presentations, and Web sites on gasification, a short course presentation was prepared. The presentation, consisting of about 500 PowerPoint slides, provides at least 7 hours of instruction tailored to an audience's interests and needs. The initial short course is scheduled to be presented September 9 and 10, 2009, in Grand Forks, North Dakota.

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

    Science.gov (United States)

    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

  12. Outcome of Prevention of Parent-to-Child Transmission of HIV in an Urban Population in Southern India.

    Science.gov (United States)

    Seenivasan, Subramani; Vaitheeswaran, Natarajan; Seetha, Viswanathan; Anbalagan, Selvaraj; Karunaianantham, Ramesh; Swaminathan, Soumya

    2015-09-01

    To analyze the outcomes of Prevention of Parent to Child Transmission (PPTCT) of HIV program in an urban Southern Indian setting. Observational study. Anti-retroviral Therapy (ART) Centers/ Integrated Counseling and Testing Centers (ICTC) at four government Obstetrics Institutes in an urban area. 100 HIV-positive pregnant women and their infants delivered in the study centers. Triple drug ART to HIV-positive pregnant women was started for maternal indications only. Rest of the pregnant women were given single dose Nevirapine (200 mg) at the onset of labor. All infants were given single dose Nevirapine (2 mg/kg) prophylaxis, according to National AIDS Control Organization guidelines. Mothers were counseled regarding breastfeeding and artificial feeding, and the choice was left to them. Whole blood HIV 1 DNA PCR was done for all infants at 6 weeks of life. A second PCR was done at 6 months or 6 weeks after stopping breastfeeds. PCR-positive infants were started on ART, and were followed-up till18 months of life. Four infants were PCR-positive for HIV. All of them were breastfed. They were born to mothers of HIV stage 1 or 2 who were not on ART as CD4 counts were >350 cells/mm3. Among the mothers in Stage 3 or 4 or CD4 count ART, none of the infants was HIV-positive. The cumulative HIV-free survival at 18 months was 94%. Parent-to-child transmission rate in HIV was low with the currently used strategies. Triple drug ART to mother reduces mother-to-child transmission despite advanced maternal stage or low CD4 counts.

  13. JV Task 125-Mercury Measurement in Combustion Flue Gases Short Course

    Energy Technology Data Exchange (ETDEWEB)

    Dennis Laudal

    2008-09-30

    The short course, designed to train personnel who have an interest in measuring mercury in combustion flue gases, was held twice at the Drury Inn in Marion, Illinois. The short course helped to provide attendees with the knowledge necessary to avoid the many pitfalls that can and do occur when measuring mercury in combustion flue gases. The first short course, May 5-8, 2008, included both a classroom-type session and hands-on demonstration of mercury-sampling equipment. The hands-on demonstration of equipment was staged at Southern Illinois Power Cooperative. Not including the Illinois Clean Coal Institute and the U.S. Department of Energy project managers, there were 12 attendees. The second short course was conducted September 16-17, 2008, but only included the classroom portion of the course; 14 people attended. In both cases, lectures were provided on the various mercury measurement methods, and interaction between attendees and EERC research personnel to discuss specific mercury measurement problems was promoted. Overall, the response to the course was excellent.

  14. Predicting the short-term risk of diabetes in HIV-positive patients

    DEFF Research Database (Denmark)

    Petoumenos, Kathy; Worm, Signe W; Fontas, Eric

    2012-01-01

    HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other...... glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV...

  15. HIV associated neurocognitive disorders (HAND in Malawian adults and effect on adherence to combination anti-retroviral therapy: a cross sectional study.

    Directory of Open Access Journals (Sweden)

    Christine M Kelly

    Full Text Available Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND among patients on combination antiretroviral therapy (cART in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART.HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery.One hundred and six HIV positive patients, with median (range age 39 (18-71 years, 73% female and median (range CD4 count 323.5 (68-1039 cells/µl were studied. Symptomatic neurocognitive impairment was present in 15% (12% mild neurocognitive disorder [MND], 3% HIV associated dementia [HAD]. A further 55% fulfilled Frascati criteria for asymptomatic neurocognitive impairment (ANI; however factors other than neurocognitive impairment could have confounded this estimate. Neither the symptomatic (MND and HAD nor asymptomatic (ANI forms of HAND were associated with subtherapeutic nevirapine/efavirenz concentrations, adjusted odds ratio 1.44 (CI. 0.234, 8.798; p = 0.696 and aOR 0.577 (CI. 0.09, 3.605; p = 0.556 respectively. All patients with subtherapeutic nevirapine/efavirenz levels had a GDS of less than 0.6, consistent with normal neurocognition.Fifteen percent of adult Malawians on cART had a diagnosis of MND or HAD. Subtherapeutic drug concentrations were found exclusively in patients with normal neurocognitive function suggesting HAND did not affect cART adherence. Further study of HAND requires more robust locally derived normative neurocognitive values and

  16. Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: a systematic review and meta-analysis.

    Science.gov (United States)

    Bera, Ebrahim; Mia, Rafiq

    2012-10-08

    The package insert for nevirapine (NVP) cautions use in HIV-infected women (including pregnant women) with CD4 counts ≥250 cells/µl. However, recent studies showed that the CD4 count of pregnant women receiving antiretroviral therapy (ART) was not predictive of NVP toxicity. To determine whether ART-naive pregnant women initiating NVP-based ART at higher CD4 counts experience greater toxicity compared with pregnant women at lower CD4 counts. We reviewed studies comparing serious adverse NVP-related events among ART-naive pregnant women who commenced therapy at higher v. lower CD4 counts. Relevant studies were extracted from PubMed, SCOPUS and EMBASE, major journals and conference proceedings prior to December 2011. Authors were contacted for additional data. Data were independently extracted and entered into Review Manager. Fourteen studies (2 663 participants) were included for analysis. The odds ratio (OR) for overall NVP toxicity among pregnant women with CD4 <250 cells/µl was 0.61 (95% confidence interval (CI) 0.43 - 0.85). When analysis was restricted to prospective studies only (7 studies, 1 318 participants), the results were consistent for overall NVP toxicity (OR 0.43; 95% CI 0.25 - 0.73) and severe hepatotoxicity (OR 0.45; 95% CI 0.22 - 0.90), but not for severe cutaneous reaction (OR 0.53; 95% CI 0.26 - 1.10). Initiating NVP-based ART during pregnancy at CD4 ≥250 cells/µl increases toxicity risk and should be avoided, necessitating urgent revision of current guidelines supporting this practice.

  17. Genotypic evaluation of etravirine sensitivity of clinical human immunodeficiency virus type 1 (HIV-1) isolates carrying resistance mutations to nevirapine and efavirenz.

    Science.gov (United States)

    Oumar, A A; Jnaoui, K; Kabamba-Mukadi, B; Yombi, J C; Vandercam, B; Goubau, P; Ruelle, J

    2010-01-01

    Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with a pattern of resistance mutations quite distinct from the current NNRTIs. We collected all routine samples of HIV-1 patients followed in the AIDS reference laboratory of UCLouvain (in 2006 and 2007) carrying resistance-associated mutations to nevirapine (NVP) or efavirenz (EFV). The sensitivity to Etravirine was estimated using three different drug resistance algorithms: ANRS (July 2008), IAS (December 2008) and Stanford (November 2008). We also verified whether the mutations described as resistance mutations are not due to virus polymorphisms by the study of 58 genotypes of NNRTI-naive patients. Sixty one samples harboured resistance to NVP and EFV: 41/61 had at least one resistance mutation to Etravirine according to ANRS-IAS algorithms; 42/61 samples had at least one resistance mutation to Etravirine according to the Stanford algorithm. 48 and 53 cases were fully sensitive to Etravirine according to ANRS-IAS and Stanford algorithms, respectively. Three cases harboured more than three mutations and presented a pattern of high-degree resistance to Etravirine according to ANRS-IAS algorithm, while one case harboured more than three mutations and presented high degree resistance to Etravirine according to the Stanford algorithm. The V1061 and V179D mutations were more frequent in the ARV-naive group than in the NNRTI-experienced one. According to the currently available algorithms, Etravirine can still be used in the majority of patients with virus showing resistance to NVP and/or EFV, if a combination of other active drugs is included.

  18. A short course in sustainable product development

    DEFF Research Database (Denmark)

    McAloone, Tim C.

    2005-01-01

    This short course in sustainable product development models, methods and mindsets is designed to fit into the Unical course on Engineering Design Methods. Three modules (called “seminars”) will guide you through . The demands for sustainable development . Professional methods for analysing and ch...... and changing products’ environmental profiles . A new approach to product service system development, where the physical product becomes an incidental aspect in the final offering to the customer...

  19. Predicting the short-term risk of diabetes in HIV-positive patients

    DEFF Research Database (Denmark)

    Petoumenos, Kathy; Worm, Signe Westring; Fontas, Eric

    2012-01-01

    Introduction: HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM ......). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of...... and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV...

  20. HIV-1–Infected Individuals in Antiretroviral Therapy React Specifically With Polyfunctional T-Cell Responses to Gag p24

    DEFF Research Database (Denmark)

    Brandt, Lea; Benfield, Thomas; Kronborg, Gitte

    2013-01-01

    Still no effective HIV-1 prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1-infected individuals on antiretroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine.......Still no effective HIV-1 prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1-infected individuals on antiretroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine....

  1. Zidovudine/lamivudine for HIV-1 infection contributes to limb fat loss.

    Directory of Open Access Journals (Sweden)

    Marit G A van Vonderen

    2009-05-01

    Full Text Available Lipoatrophy is known to be associated with stavudine as part of the treatment for HIV infection, but it is less clear if this serious side effect is also related to other nucleoside reverse transcriptase inhibitors like zidovudine. We aimed to determine whether zidovudine-sparing first-line antiretroviral therapy would lead to less lipoatrophy and other metabolic changes than zidovudine-containing therapy.Fifty antiretroviral therapy-naïve HIV-1 infected men with an indication to start antiretroviral therapy were included in a randomized single blinded clinical trial. Randomisation was between zidovudine-containing therapy (zidovudine/lamivudine+lopinavir/ritonavir and zidovudine-sparing therapy (nevirapine+lopinavir/ritonavir. Main outcome measures were body composition assessed by computed tomography and dual-energy X-ray absorptiometry scan and lipid profile before and after 3, 12, 24 months of antiretroviral therapy. In the zidovudine/lamivudine+lopinavir/ritonavir group, from 3 months onward limb fat decreased progressively by 684+/-293 grams (estimated mean+/-standard error of the mean(p = 0.02 up to 24 months whereas abdominal fat increased, but exclusively in the visceral compartment (+21.9+/-8.1 cm(2, p = 0.008. In contrast, in the nevirapine+lopinavir/ritonavir group, a generalized increase in fat mass was observed. After 24 months no significant differences in high density lipoprotein and total/high density lipoprotein cholesterol ratio were found between both treatment groups, but total and low density lipoprotein cholesterol levels were higher in the nevirapine+lopinavir/ritonavir group (6.1+/-0.2 versus 5.3+/-0.2 and 3.6+/-0.1 versus 2.8+/-0.1 mmol/l respectively, p<0.05. Virologic response and safety were comparable in both groups.Zidovudine/lamivudine+lopinavir/ritonavir, but not nevirapine+lopinavir/ritonavir in antiretroviral therapy-naïve patients, is associated with lipoatrophy and greater relative intraabdominal

  2. Planning horizon affects prophylactic decision-making and epidemic dynamics.

    Science.gov (United States)

    Nardin, Luis G; Miller, Craig R; Ridenhour, Benjamin J; Krone, Stephen M; Joyce, Paul; Baumgaertner, Bert O

    2016-01-01

    The spread of infectious diseases can be impacted by human behavior, and behavioral decisions often depend implicitly on a planning horizon-the time in the future over which options are weighed. We investigate the effects of planning horizons on epidemic dynamics. We developed an epidemiological agent-based model (along with an ODE analog) to explore the decision-making of self-interested individuals on adopting prophylactic behavior. The decision-making process incorporates prophylaxis efficacy and disease prevalence with the individuals' payoffs and planning horizon. Our results show that for short and long planning horizons individuals do not consider engaging in prophylactic behavior. In contrast, individuals adopt prophylactic behavior when considering intermediate planning horizons. Such adoption, however, is not always monotonically associated with the prevalence of the disease, depending on the perceived protection efficacy and the disease parameters. Adoption of prophylactic behavior reduces the epidemic peak size while prolonging the epidemic and potentially generates secondary waves of infection. These effects can be made stronger by increasing the behavioral decision frequency or distorting an individual's perceived risk of infection.

  3. HIV after 40 in rural South Africa: A life course approach to HIV vulnerability among middle aged and older adults.

    Science.gov (United States)

    Mojola, Sanyu A; Williams, Jill; Angotti, Nicole; Gómez-Olivé, F Xavier

    2015-10-01

    South Africa has the highest number of people living with HIV in the world (over 6 million) as well as a rapidly aging population, with 15% of the population aged 50 and over. High HIV prevalence in rural former apartheid homeland areas suggests substantial aging with HIV and acquisition of HIV at older ages. We develop a life course approach to HIV vulnerability, highlighting the rise and fall of risk and protection as people age, as well as the role of contextual density in shaping HIV vulnerability. Using this approach, we draw on an innovative multi-method data set collected within the Agincourt Health and Demographic Surveillance System in South Africa, combining survey data with 60 nested life history interviews and 9 community focus group interviews. We examine HIV risk and protective factors among adults aged 40-80, as well as how and why these factors vary among people at older ages. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Statistical inference a short course

    CERN Document Server

    Panik, Michael J

    2012-01-01

    A concise, easily accessible introduction to descriptive and inferential techniques Statistical Inference: A Short Course offers a concise presentation of the essentials of basic statistics for readers seeking to acquire a working knowledge of statistical concepts, measures, and procedures. The author conducts tests on the assumption of randomness and normality, provides nonparametric methods when parametric approaches might not work. The book also explores how to determine a confidence interval for a population median while also providing coverage of ratio estimation, randomness, and causal

  5. Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis.

    Science.gov (United States)

    Mbeye, Nyanyiwe M; ter Kuile, Feiko O; Davies, Mary-Ann; Phiri, Kamija S; Egger, Matthias; Wandeler, Gilles

    2014-09-01

    Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children. © 2014 John Wiley & Sons Ltd.

  6. Prophylactic antibiotic for pacemaker surgery: what is optimal ...

    African Journals Online (AJOL)

    One of them, a bed-ridden patient developed severe pocket infection necessitating explantation and replacement 3 weeks later. Conclusions: We noted with satisfaction that short regime of prophylactic parentral ceftriaxone is effective in preventing pacemaker infection and there is no need for the long regimen. Niger Med J.

  7. [Obesity, high blood pressure, hypercholesterolaemia, and untreated diabetes in HIV-infected and HIV-uninfected Adults in Mbuji-Mayi (Democratic republic of congo)].

    Science.gov (United States)

    Mukeba-Tshialala, D; Nachega, J B; Mutombo-Tshingwali, M; Arendt, V; Gilson, G; Moutschen, M

    2017-12-01

    Little is known about the major cardiovascular risk factors in HIV-infected as compared to the HIV-uninfected patients in the Democratic Republic of Congo (DR Congo). We determined the prevalence of hypertension, obesity (BMI ≥ 30 kg/m 2 ), total cholesterol > 200 mg/dl, HDLcholesterol &≤ 40 mg/dl, and glycemia > 126 mg/dl. We also calculated the average and/or median of total cholesterol, HDL-cholesterol, and glycemia among HIV-infected and HIV-uninfected patients.We conducted a cross-sectional study that enrolled 592 HIV-uninfected and 445 HIV-infected patients of whom 425 (95.5%) were on first-line antiretroviral therapy based on stavudine-lamivudine-nevirapine. Clinical and laboratory data of the patients were collected. The results were analyzed by chi-square, t-student, and Wilcoxon rank sum tests. 11.5% of HIV-infected patients had an average blood pressure suggesting hypertension versus 10.6% of HIV-uninfected (P = 0.751). But in absolute value, HIVinfected patients had a median of diastolic blood pressure of 90 mmHg versus 85 mmHg of HIV-uninfected (P 200 mg/dl and HDL-cholesterol ≤ 40 mg/dl. Proactive screening and prompt management of dyslipidemia and hypertension in this population should be a priority.

  8. Blended Learning Approach of the Flipped Model for Partograph Short Course

    Directory of Open Access Journals (Sweden)

    Linawati Linawati

    2016-08-01

    Full Text Available Crucial demand of professional and well-trained midwives, midwifery lecturers, general practitioner, and OBGYN in Indonesia could be fulfilled by providing effective learning process to them. Udayana University through its Distance Learning Centre has offered Partograph short course in order to respond the demand. The short course has implemented blended learning approach of the flipped classroom with international collaboration. The course was joint by participants from 11 countries through video conference.  The course was well designed, conducted follow Global Development Learning Network standard, and then it was evaluated.  The course yielded high impact to the participants which could be seen from the participants’ feedback. They testified that the course was marvelous, effective and informative. Finally the evaluation results showed that all components of the learning process have significant result to the overall learning quality which was shown by their correlation coefficients.

  9. HIV after 40 in Rural South Africa1: A Life Course Approach to HIV Vulnerability among Middle Aged and Older Adults

    Science.gov (United States)

    Williams, Jill; Angotti, Nicole; Gómez-Olivé, Xavier

    2015-01-01

    South Africa has the highest number of people living with HIV in the world (over 6 million) as well as a rapidly aging population, with 15% of the population aged 50 and over. High HIV prevalence in rural former apartheid homeland areas suggests substantial aging with HIV and acquisition of HIV at older ages. We develop a life course approach to HIV vulnerability, highlighting the rise and fall of risk and protection as people age, as well as the role of contextual density in shaping HIV vulnerability. Using this approach, we draw on an innovative multi-method data set collected within the Agincourt Health and Demographic Surveillance System in South Africa, combining survey data with 60 nested life history interviews and 9 community focus group interviews. We examine HIV risk and protective factors among adults aged 40–80, as well as how and why these vary among people at older ages. PMID:26364007

  10. Development of drug resistance in patients receiving combinations of zidovudine, didanosine and nevirapine

    NARCIS (Netherlands)

    Conway, B.; Wainberg, M. A.; Hall, D.; Harris, M.; Reiss, P.; Cooper, D.; Vella, S.; Curry, R.; Robinson, P.; Lange, J. M.; Montaner, J. S.

    2001-01-01

    OBJECTIVE: To evaluate the development of phenotypic and genotypic resistance to zidovudine, didanosine and nevirapine as a function of the virologic response to therapy in a group of drug-naive individuals receiving various combinations of these agents. DESIGN: All patients were enrolled in a

  11. Sexual behavior, risk perception, and HIV transmission can respond to HIV antiviral drugs and vaccines through multiple pathways

    OpenAIRE

    Stephen Tully; Monica Cojocaru; Chris T. Bauch

    2015-01-01

    There has been growing use of highly active antiretroviral treatment (HAART) for HIV and significant progress in developing prophylactic HIV vaccines. The simplest theories of counterproductive behavioral responses to such interventions tend to focus on single feedback mechanisms: for instance, HAART optimism makes infection less scary and thus promotes risky sexual behavior. Here, we develop an agent based, age-structured model of HIV transmission, risk perception, and partner selection in a...

  12. Plasma HIV-1 tropism and risk of short-term clinical progression to AIDS or death

    DEFF Research Database (Denmark)

    Fontdevila, Maria Casadellà; Cozzi-Lepri, Alessandro; Phillips, Andrew

    2014-01-01

    INTRODUCTION: It is uncertain if plasma HIV-1 tropism is an independent predictor of short-term risk of clinical progression / death, in addition to the CD4 count and HIV RNA level. We conducted a nested case-control study within EuroSIDA to assess this question amongst people with current HIV RNA...

  13. A New Validated RP- HPLC Method for the Determination of Nevirapine in Human Plasma

    Directory of Open Access Journals (Sweden)

    C. H. Venkata Kumar

    2010-01-01

    Full Text Available A rapid, selective and sensitive high performance liquid chromatographic method for the estimation of nevirapine in human plasma has been developed. Chromatography was carried out on a Hypersil BDS C18 column using a mixture of ammonium acetate buffer (pH 4.0 ± 0.05 and acetonitrile (85:15 v/v as the mobile phase. The eluents were monitored for the drug by UV detection at 254 nm. Oxcarbazepine was used as an internal standard for this study. The retention times for nevirapine and oxcarbazepine were found to be 7.2 and 14.7 min respectively. The method was found to be linear in the concentration range of 50 ng/mL to 5003.7 ng/mL. The method was validated as per FDA guidelines and was found to be suitable for bioequivalence and pharmacokinetic studies.

  14. Identifying HIV-1 dual infections

    Directory of Open Access Journals (Sweden)

    Cornelissen Marion

    2007-09-01

    Full Text Available Abstract Transmission of human immunodeficiency virus (HIV is no exception to the phenomenon that a second, productive infection with another strain of the same virus is feasible. Experiments with RNA viruses have suggested that both coinfections (simultaneous infection with two strains of a virus and superinfections (second infection after a specific immune response to the first infecting strain has developed can result in increased fitness of the viral population. Concerns about dual infections with HIV are increasing. First, the frequent detection of superinfections seems to indicate that it will be difficult to develop a prophylactic vaccine. Second, HIV-1 superinfections have been associated with accelerated disease progression, although this is not true for all persons. In fact, superinfections have even been detected in persons controlling their HIV infections without antiretroviral therapy. Third, dual infections can give rise to recombinant viruses, which are increasingly found in the HIV-1 epidemic. Recombinants could have increased fitness over the parental strains, as in vitro models suggest, and could exhibit increased pathogenicity. Multiple drug resistant (MDR strains could recombine to produce a pan-resistant, transmittable virus. We will describe in this review what is presently known about super- and re-infection among ambient viral infections, as well as the first cases of HIV-1 superinfection, including HIV-1 triple infections. The clinical implications, the impact of the immune system, and the effect of anti-retroviral therapy will be covered, as will as the timing of HIV superinfection. The methods used to detect HIV-1 dual infections will be discussed in detail. To increase the likelihood of detecting a dual HIV-1 infection, pre-selection of patients can be done by serotyping, heteroduplex mobility assays (HMA, counting the degenerate base codes in the HIV-1 genotyping sequence, or surveying unexpected increases in the

  15. Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Komaki, Ritsuko; Meyers, Christina A; Shin, Dong M; Garden, Adam S; Byrne, Kevin; Nickens, Judy A; Cox, James D

    1995-08-30

    Purpose: Cognitive deficits after treatment for small cell lung cancer (SCLC) have been attributed to prophylactic cranial irradiation (PCI). A prospective study of neuropsychological function was undertaken to document the evolution and magnitude of neuropsychologic deficits. Methods and Materials: Thirty patients with limited stage SCLC who responded well (29 complete response (CR), 1 partial response (PR)) to combination chemotherapy plus thoracic irradiation or resection were studied with neuropsychological tests in the cognitive domains of intelligence, frontal lobe function, language, memory, visual-perception, and motor dexterity prior to a planned course of PCI. Nine patients had a neurologic history that could influence testing. Results: An unexpected 97% (29 out of 30) of patients had evidence of cognitive dysfunction prior to PCI. The most frequent impairment was verbal memory, followed by frontal lobe dysfunction, and fine motor incoordination. Of the patients with no prior neurologic or substance abuse history, 20 out of 21 (95%) had impairments on neuropsychological assessment. This neurologically normal group was just as impaired as the group with such a history with respect to delayed verbal memory and frontal lobe executive function. Eleven patients had neuropsychological testing 6 to 20 months after PCI; no significant differences were found from their pretreatment tests. Conclusions: A high proportion of neurologically normal patients with limited SCLC and favorable responses to combination chemotherapy have specific cognitive deficits before receiving PCI. Short-term (6 to 20 months) observations after PCI have shown no significant deterioration.

  16. Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation

    International Nuclear Information System (INIS)

    Komaki, Ritsuko; Meyers, Christina A.; Shin, Dong M.; Garden, Adam S.; Byrne, Kevin; Nickens, Judy A.; Cox, James D.

    1995-01-01

    Purpose: Cognitive deficits after treatment for small cell lung cancer (SCLC) have been attributed to prophylactic cranial irradiation (PCI). A prospective study of neuropsychological function was undertaken to document the evolution and magnitude of neuropsychologic deficits. Methods and Materials: Thirty patients with limited stage SCLC who responded well (29 complete response (CR), 1 partial response (PR)) to combination chemotherapy plus thoracic irradiation or resection were studied with neuropsychological tests in the cognitive domains of intelligence, frontal lobe function, language, memory, visual-perception, and motor dexterity prior to a planned course of PCI. Nine patients had a neurologic history that could influence testing. Results: An unexpected 97% (29 out of 30) of patients had evidence of cognitive dysfunction prior to PCI. The most frequent impairment was verbal memory, followed by frontal lobe dysfunction, and fine motor incoordination. Of the patients with no prior neurologic or substance abuse history, 20 out of 21 (95%) had impairments on neuropsychological assessment. This neurologically normal group was just as impaired as the group with such a history with respect to delayed verbal memory and frontal lobe executive function. Eleven patients had neuropsychological testing 6 to 20 months after PCI; no significant differences were found from their pretreatment tests. Conclusions: A high proportion of neurologically normal patients with limited SCLC and favorable responses to combination chemotherapy have specific cognitive deficits before receiving PCI. Short-term (6 to 20 months) observations after PCI have shown no significant deterioration

  17. Prevalence and management of intestinal helminthiasis among HIV-infected patients at Muhimbili National Hospital.

    Science.gov (United States)

    Mwambete, Kennedy D; Justin-Temu, Mary; Peter, Sharon

    2010-01-01

    A cross-sectional study was conducted at Muhimbili National Hospital (Tanzania) to determine prevalence of helminthiasis among in-patients with HIV/AIDS. After signing an informed consent form, participants answered a sociodemographic and risk factor questionnaire. Fecal specimens from patients with HIV-infected and uninfected patients were screened for intestinal helminthiasis (IHLs) using coprological methods. A total of 146 patients were recruited, of those 66 were HIV-negative while 80 were HIV-negative patients. Thirty-five patients (12 HIV/AIDS and 23 non-HIV/AIDS) had helminthic infections. Hookworms were the most frequently detected helminths among patients living with HIV/AIDS (13.6%) and HIV-negative patients (17.5%), followed by schistosomiasis (9%) detected among HIV-negative individuals only. Prevalence of helminthiases (HLs) was observed to be relatively lower among HIV-infected than uninfected patients, which is ascribable to prophylactic measures adopted for patients with HIV/AIDS. Thus, it is recommended that routine screening for HLs and prophylactic measures should be adopted for the improvement of patients' health status.

  18. Short Course in the Microbiome

    Directory of Open Access Journals (Sweden)

    Kimberly Falana

    2015-07-01

    Full Text Available Over the past decade, it has become evident that the microbiome is an important environmental factor that affects many physiological processes, such as cell proliferation and differentiation, behaviour, immune function and metabolism. More importantly, it may contribute to a wide variety of diseases, including cancer, inflammatory diseases, metabolic diseases and responses to pathogens. We expect that international, integrative and interdisciplinary translational research teams, along with the emergence of FDA-approved platforms, will set the framework for microbiome-based therapeutics and diagnostics. We recognize that the microbiome ecosystem offers new promise for personalized/precision medicine and targeted treatment for a variety of diseases. The short course was held as a four-session webinar series in April 2015, taught by pioneers and experts in the microbiome ecosystem, covering a broad range of topics from the healthy microbiome to the effects of an altered microbiome from neonates to adults and the long term effects as it is related to disease, from asthma to cancer. We have learned to appreciate how beneficial our microbes are in breaking down our food, fighting off infections and nurturing our immune system, and this information provides us with ideas as to how we can manipulate our microbiome to prevent certain diseases. However, given the variety of applications, there are scientific challenges, though there are very promising areas in reference to the clinical benefits of understanding more about our microbiome, whether in our gut or on our skin: the outlook is bright. A summary of the short course is presented as a meeting dispatch.

  19. Modelling formulae of strawberry whey drinks of prophylactic application

    Directory of Open Access Journals (Sweden)

    N. Tkachenko

    2017-04-01

    Full Text Available Expediency of the development of formulae and innovative technologies for production of prophylactic application drinks possessing antioxidant, probiotic and hepatoprotective properties with the use of the secondary dairy product – whey, as well as the domestic vegetable raw materials having a high content of bioactive substances has been substantiated.Formulation composition of the prophylactic drinks based on cheese whey, extract of Tagetes patula flowers and the berry filler “Strawberry” with the use of the response surface method has been developed. Bioactivity of the drinks and the complex quality indicator which accounts for the total influence of the bioactivity, organoleptic assessment and weight coefficients of the specified unit indicators were taken as the optimization criteria; as the independent factors that were varied in the course of the experiment, the mass fractions of the marigold flowers extract and the strawberries filler were selected. It is recommended that the mass fractions of the berry filler “Strawberry” and the extract of Tagetes patula flowers in the prophylactic drinks are set as 7 and 20 % of the finished product, accordingly. The practical mass fraction of the citric acid of 0.2 % was determined as it ensures high organoleptic characteristics of the finished drinks. Recommendations are given concerning development of innovative technologies of unfermented and fermented strawberry whey drinks of prophylactic application enriched with the extract of Tagetes patula flowers.

  20. Expanding the domain of drug delivery for HIV prevention: exploration of the transdermal route.

    Science.gov (United States)

    Puri, Ashana; Sivaraman, Arunprasad; Zhang, Wei; Clark, Meredith R; Banga, Ajay K

    2017-01-01

    Constant efforts for HIV prevention using antiretroviral drugs, pre- and postexposure prophylactic agents, and microbicides are being made by researchers. Drug-delivery systems such as oral tablets and coitally dependent vaginal gels are short acting, require daily application, and are associated with user adherence issues, whereas the coitally independent systems such as injectables and biodegradable implants are long acting, lasting several months, during which time the termination of prophylaxis is impractical in case of adverse effects. An effective drug-delivery system to be used for an intermediate duration, if available, would be an attractive alternative option for users in terms of adherence. Transdermal delivery systems, overcoming most of the limitations of the other routes of administration and aiming to provide sustained delivery of drugs through skin, may be explored for HIV prevention. Passive and physical enhancement techniques may be designed strategically to improve the transdermal delivery of HIV preventive agents.

  1. Community in a Hurry: Social Contracts and Social Covenants in Short-Term ESL Courses

    Science.gov (United States)

    Martinsen, Rob A.

    2009-01-01

    Like many adult ESL instructors, the author has felt firsthand the challenges of creating community in short-term courses. Through his experience, he has noticed that in order to successfully build community in short-term ESL courses, teachers need to lay a foundation for social contracts and social covenants from the first day of the course and…

  2. Short-course Astronomical Research Seminars for High School and College Students

    Science.gov (United States)

    Johnson, Jolyon

    2011-05-01

    Since 2008, I have helped lead several short-course astronomical research seminars with Russell M. Genet. These seminars have ranged from semester-long courses at Cuesta College in San Luis Obispo, California to long weekends at the University of Oregon's Pine Mountain Observatory. Each seminar is led by an experienced observer or group of observers who guide high school and college students through the scientific process from observations to publication. The students (anywhere from half a dozen to twenty in number) participate in and contribute to every step. Being a coauthor on one or more research papers offers students an advantage on college and scholarship applications. Similarly, graduate schools often prefer students with research experience. Many topics of research are appropriate for these short-courses including variable star, exoplanet, and asteroid photometry. However, the most successful topic has been visual double stars because the observations required are straitforward and the equipment is relatively inexpensive. The Journal of Double Star Observations is also welcoming of student research and provides swift publication. A detailed description of the short-course seminars can be found in the recent Collins Foundation Press volume titled Small Telescopes and Astronomical Research.

  3. Benefits of prophylactic gastropexy for dogs at risk of gastric dilatation-volvulus.

    Science.gov (United States)

    Ward, Michael P; Patronek, Gary J; Glickman, Lawrence T

    2003-09-12

    The lifetime probability of death from gastric dilation-volvulus (GDV) for five dog breeds was estimated based on published breed-specific longevity and GDV incidence. These breeds were Great Dane, Irish Setter, Rottweiler, Standard Poodle and Weimaraner. Lifetime risk (95% CI) of GDV in these breeds ranged from 3.9% (0-11.2%) for Rottweiler to 36.7% (25.2-44.6%) for Great Dane. A decision-tree analysis for prophylactic gastropexy--using lifetime probability of death from GDV and expected cost savings for veterinary services as outcome measures--was undertaken to determine the preferred course of action in several dog breeds. Prophylactic gastropexy was the preferred choice of action for all breeds examined, with the reduction in mortality (versus no gastropexy) ranging from 2.2-fold (Rottweiler) to 29.6-fold (Great Dane). Assuming a prophylactic gastropexy costs US$ 400, the procedure was cost-effective when the lifetime risk of GDV was > or = 34%. The maximum and minimum estimated breakeven costs for the gastopexy procedure ranged from US$ 20 (Rottweiler) to US$ 435 (Great Dane). The cost-effectiveness of prophylactic gastropexy was most sensitive to the cost of treating GDV (US$ 1500). Prophylactic gastropexy raises ethical issues that need to be considered by veterinarians and dog breeders.

  4. The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Daniëlle van Manen

    2008-02-01

    Full Text Available The antiviral factor tripartite interaction motif 5alpha (Trim5alpha restricts a broad range of retroviruses in a species-specific manner. Although human Trim5alpha is unable to block HIV-1 infection in human cells, a modest inhibition of HIV-1 replication has been reported. Recently two polymorphisms in the Trim5 gene (H43Y and R136Q were shown to affect the antiviral activity of Trim5alpha in vitro. In this study, participants of the Amsterdam Cohort studies were screened for polymorphisms at amino acid residue 43 and 136 of the Trim5 gene, and the potential effects of these polymorphisms on the clinical course of HIV-1 infection were analyzed. In agreement with the reported decreased antiviral activity of Trim5alpha that contains a Y at amino acid residue 43 in vitro, an accelerated disease progression was observed for individuals who were homozygous for the 43Y genotype as compared to individuals who were heterozygous or homozygous for the 43H genotype. A protective effect of the 136Q genotype was observed but only after the emergence of CXCR4-using (X4 HIV-1 variants and when a viral load of 10(4.5 copies per ml plasma was used as an endpoint in survival analysis. Interestingly, naive CD4 T cells, which are selectively targeted by X4 HIV-1, revealed a significantly higher expression of Trim5alpha than memory CD4 T cells. In addition, we observed that the 136Q allele in combination with the -2GG genotype in the 5'UTR was associated with an accelerated disease progression. Thus, polymorphisms in the Trim5 gene may influence the clinical course of HIV-1 infection also underscoring the antiviral effect of Trim5alpha on HIV-1 in vivo.

  5. The Effect of Trim5 Polymorphisms on the Clinical Course of HIV-1 Infection

    Science.gov (United States)

    van Manen, Daniëlle; Rits, Maarten A. N; Beugeling, Corrine; van Dort, Karel; Schuitemaker, Hanneke; Kootstra, Neeltje A

    2008-01-01

    The antiviral factor tripartite interaction motif 5α (Trim5α) restricts a broad range of retroviruses in a species-specific manner. Although human Trim5α is unable to block HIV-1 infection in human cells, a modest inhibition of HIV-1 replication has been reported. Recently two polymorphisms in the Trim5 gene (H43Y and R136Q) were shown to affect the antiviral activity of Trim5α in vitro. In this study, participants of the Amsterdam Cohort studies were screened for polymorphisms at amino acid residue 43 and 136 of the Trim5 gene, and the potential effects of these polymorphisms on the clinical course of HIV-1 infection were analyzed. In agreement with the reported decreased antiviral activity of Trim5α that contains a Y at amino acid residue 43 in vitro, an accelerated disease progression was observed for individuals who were homozygous for the 43Y genotype as compared to individuals who were heterozygous or homozygous for the 43H genotype. A protective effect of the 136Q genotype was observed but only after the emergence of CXCR4-using (X4) HIV-1 variants and when a viral load of 104.5 copies per ml plasma was used as an endpoint in survival analysis. Interestingly, naive CD4 T cells, which are selectively targeted by X4 HIV-1, revealed a significantly higher expression of Trim5α than memory CD4 T cells. In addition, we observed that the 136Q allele in combination with the −2GG genotype in the 5′UTR was associated with an accelerated disease progression. Thus, polymorphisms in the Trim5 gene may influence the clinical course of HIV-1 infection also underscoring the antiviral effect of Trim5α on HIV-1 in vivo. PMID:18248091

  6. Directly Observed Treatment Short Course (DOTS) appears to have ...

    African Journals Online (AJOL)

    Directly Observed Treatment Short Course (DOTS) appears to have reduced the self-care role of pulmonary tuberculosis patient: evidence from a correctional study between Personal Health Beliefs (PHB) and Self Care Practices (SCP)

  7. [HIV infection in the Stavropol' region].

    Science.gov (United States)

    Filonenko, N G; Isaev, V P; Pelikh, N L

    2001-01-01

    The data on the dynamics of HIV infection in the Stavropol Territory beginning with 1987 are given. The situation became aggravated after 1996, and its sharp deterioration occurred in 2000 when 138 cases of HIV infection were detected and the area of this infection increased. In most cases patients became infected beyond the borders of the territory. About a half of the new cases of HIV infection registered in 2000 were detected in Ingushetia and Chechnya. The leading factor in the spread of HIV infection was the use of drugs by injection. The main trends of the prophylactic work are presented.

  8. HIV and pregnancy: Maternal and neonatal evolution HIV y embarazo: Evolución materna y neonatal

    Directory of Open Access Journals (Sweden)

    Diego Cecchini

    2011-10-01

    Full Text Available Data regarding epidemiological aspects, antiretroviral drug safety, and outcomes of HIV-infected pregnant women and their newborns are limited in Argentina. We underwent a retrospective analysis of registries of HIV-infected pregnant women assisted at Helios Salud, Buenos Aires, Argentina (1997-2006. Variables associated with preterm delivery and neonatal complications were analyzed by univariate and logistic regression analyses. A total of 204 mother-child binomium were included. Maternal age (median: 29 years; 32.5% without prior diagnosis of HIV-infection. Baseline median CD4 T-cell count: 417 cell/μl; 98% received antiretroviral drugs during pregnancy [2 nucleoside analogs plus either nevirapine (55% or a protease inhibitor (32%]. Overall incidence of toxicity was 12.5%: rash (8%, anemia (3.5% and hepatotoxicity (1%. Rash was associated with exposure to nevirapine. Eighty one percent and 50% reached HIV-viral loads La información sobre aspectos epidemiológicos, seguridad de drogas antirretrovirales y evolución de mujeres embarazadas HIV positivas y sus hijos es limitada en la Argentina. Realizamos un análisis retrospectivo de registros de embarazadas HIV positivas asistidas en Helios Salud, Buenos Aires, Argentina (1997-2006. Las variables asociadas con parto prematuro y complicaciones neonatales se estudiaron mediante análisis univariado y regresión logística. Estudiamos 204 binomios madre-hijo. Edad materna (mediana: 29 años, 32.5% sin diagnóstico previo de HIV. Recuento de linfocitos T CD4+ (mediana: 417 células/μl. El 98% recibió tratamiento antirretroviral durante el embarazo [dos análogos de nucleósidos más nevirapina (55% o un inhibidor de proteasa (32%]. La incidencia global de toxicidad fue 12.5%: erupción cutánea (8%, anemia (3.5% y hepatotoxicidad (1%. La exposición a nevirapina se asoció con rash. El 81% y 50% alcanzaron cargas virales <1000 y <50 copias/ml preparto, respectivamente. Cesárea programada: 68

  9. FEATURES OF COURSE OF PREGNANCY AND DELIVERY IN HIV-INFECTED WOMEN WITH A PREMATURE BIRTH

    Directory of Open Access Journals (Sweden)

    Ольга Александровна Яковлева

    2018-01-01

    Full Text Available The aim of the research – identify features of the course of pregnancy, childbirth and the postpartum period in HIV-infected women with preterm labor. Materials and methods. A retrospective study was conducted, which included 87 pregnant HIV-positive women with preterm birth for the period 2008-2016, which was 43.2 % of all deliveries in HIV-positive women. The epidemiological, clinical and anamnestic data, the characteristics of the course of pregnancy, childbirth and the postpartum period, methods of delivery and the state of newborns were assessed. Results. The average age of the patients was 27 ± 5.2 years. The diagnosis of HIV infection was established before pregnancy in 53.2 %, during pregnancy – in 46.8 % (in the first trimester – in 12.8 %, in II – in 27.6 %, in III – in 6.4 %. In the first trimester antiretroviral therapy was started in 48.9 % of pregnant women, in II – in 36.2 %, in III – in 6.4 %, 8.5 % of patients did not perform chemoprophylaxis during pregnancy. The course of pregnancy was complicated by the threat of termination of pregnancy in 27.7 % of patients, placental insufficiency with fetal retardation – in 38.3 %, gestational edema – in 14.9 %, toxic hepatitis – in 27.7 %, polyhydramnios – in 4.3 %, anhydrite – in 6.4 %, thrombocytopenia – in 8.5 %. Very early premature births accounted for 7 %, early – 68 %, late premature birth – 25 %. 35 % of infants had a delay in fetal development of 1-2 degrees, 87 % had a diagnosis of cerebral ischemia of 1-2 degrees, but respiratory failure was observed only in 15 % of cases. Conclusion. The percentage of preterm delivery in HIV-infected patients is much higher than in the population. HIV infection is a risk factor for premature delivery. Among complications of pregnancy in HIV-infected women, there is often a threat of interruption, placental insufficiency, delayed fetal growth. Among the pathologies of newborns

  10. Short course review and the future

    Energy Technology Data Exchange (ETDEWEB)

    Corden, Pierce S. [Center for Science, Technology and Security Policy, American Association for the Advancement of Science, Washington, DC 20005 (United States)

    2014-05-09

    The presentations at the short course that were the basis of the present Proceedings covered many critical issues related to the objective of eliminating nuclear weapons as a means of ensuring global security and stability. This paper is based on the concluding talk, which briefly reviewed the course, offered a net assessment of where the project of elimination - a policy objective for nearly all the world's states - stands, and discussed some of the factors that need to be dealt with in achieving a nuclear weapon free world. These include understanding what 'proliferation' means and how it has changed over time, how the spread of nuclear weapons has proceeded over time, both 'vertical' in numbers and 'horizontal' to additional countries, what way the 'vector' of reversing proliferation is pointing, and the roles of nuclear energy and international governance.

  11. Hidradenitis suppurativa in a HIV-infected child

    Directory of Open Access Journals (Sweden)

    G Prabhu

    2012-01-01

    Full Text Available Hidradenitis suppurativa (HS, a painful and chronic condition, commonly occurs in women and coincides with post-pubertal increase in sex hormones. A 13-year-old pre-pubertal HIV-infected male child presented to our clinic with a discharging right axillary lymph node swelling. The biopsy of the lesion showed features of HS. The patient was treated with oral antibiotics, oral steroids, and local antibiotic wash. Though the patient responded to this treatment, the clinical response was not adequate and the lesion recurred. Subsequently, the child was started on antiretroviral therapy (zidovudine, lamivudine, and nevirapine. Following these medications, the lesions healed and had not recurred till we last examined the child. Thus, this is a rare presentation of a known condition in an HIV-infected pre-pubertal male child, which did not respond to usual modalities of treatment and had to be treated with antiretroviral therapy.

  12. Age and life course location as interpretive resources for decisions regarding disclosure of HIV to parents and children: Findings from the HIV and later life study.

    Science.gov (United States)

    Rosenfeld, Dana; Ridge, Damien; Catalan, Jose; Delpech, Valerie

    2016-08-01

    Studies of disclosure amongst older people living with HIV (PLWH) are uninformed by critical social-gerontological approaches that can help us to appreciate how older PLWH see and treat age as relevant to disclosure of their HIV status. These approaches include an ethnomethodologically-informed social constructionism that explores how 'the' life course (a cultural framework depicting individuals' movement through predictable developmental stages from birth to death) is used as an interpretive resource for determining self and others' characteristics, capacities, and social circumstances: a process Rosenfeld and Gallagher (2002) termed 'lifecoursing'. Applying this approach to our analysis of 74 life-history interviews and three focus groups with older (aged 50+) people living with HIV in the United Kingdom, we uncover the central role that lifecoursing plays in participants' decision-making surrounding disclosure of their HIV to their children and/or older parents. Analysis of participants' accounts uncovered four criteria for disclosure: the relevance of their HIV to the other, the other's knowledge about HIV, the likelihood of the disclosure causing the other emotional distress, and the other's ability to keep the disclosed confidential. To determine if these criteria were met in relation to specific children and/or elders, participants engaged in lifecoursing, evaluating the other's knowledge of HIV, and capacity to appropriately manage the disclosure, by reference to their age. The use of assumptions about age and life-course location in decision-making regarding disclosure of HIV reflects a more nuanced engagement with age in the disclosure decision-making process than has been captured by previous research into HIV disclosure, including on the part of people aging with HIV. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8(+ T cell responses in HIV-1-infected individuals.

    Directory of Open Access Journals (Sweden)

    Núria Climent

    Full Text Available Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B in human monocyte-derived dendritic cells (MDDC and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α. MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8(+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8(+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4(+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

  14. Classification of prophylactic antiradiation drugs as the consistency of conceptual basis of current radiation pharmacology

    International Nuclear Information System (INIS)

    Vasin, M.F

    1999-01-01

    The consistency of the classification of prophylactic antiradiation drugs have been given consideration as history of their discovery, theory of the radioprotection mechanisms and their use in applied medicine. Prophylactic drugs consists of radioprotectors with short-term of long-term action, drugs stimulating radioresistance, the ones suppressing symptoms of primary radiation reaction, the ones of early detoxication, the ones for adsorption and elimination of radionuclides from an organism [ru

  15. Evaluation of short course drug therapy for tuberculosis in pediatric ward of Imam Khomeini Hospital

    Directory of Open Access Journals (Sweden)

    Daneshjoo Kh

    1999-07-01

    Full Text Available Tuberculosis appears to be a disease as old as human history. Tuberculosis is of great public health importance in the developing countries. Its clinical profile is different in developing countries in comparison to countries of Europe and North America. The recent epidemic of HIV has slowed down the declining trend in the incidence of tuberculosis. Bacilli are transmitted from one infected person to the others as an aerosol. In some cases contaminated milk may also be responsible. However despite effective regimens and addition of new drugs and improved pharmacokinetic knowledge the chemotherapy of tuberculosis still remains a challenge. Poor drug-compliance by patients being one of the foremost reason for frequent relapses and bacterial resistance. Some important and concrete steps to meet these challenges have been judicious use of two or more bactericidal drugs and introduction of short courses regiment. Multiple drugs therapy may shorten the duration of treatment and prevent emergence of drug resistance.

  16. Sex differences in apolipoprotein A1 and nevirapine-induced toxicity

    OpenAIRE

    Aline Marinho; Clara Dias; Alexandra Antunes; Umbelina Caixas; Teresa Branco; Matilde Marques; Emília Monteiro; Sofia Pereira

    2014-01-01

    Nevirapine (NVP) is associated with severe liver and skin toxicity through sulfotransferase (SULT) bioactivation of the phase I metabolite 12-hydroxy-NVP [1–3]. The female sex, a well-known risk factor for NVP-induced toxicity, is associated with higher SULT expression [4] and lower plasma levels of 12-hydroxy-NVP [3]. Interestingly, apolipoprotein A1 (ApoA1) increases SULT2B1 activity and ApoA1 synthesis is increased by NVP [5, 6]. Herein, we explore the effect of ApoA1 levels on NVP metabol...

  17. Prevalence and management of helminthiasis among underfives living with HIV/AIDS at Amana Hospital, Tanzania.

    Science.gov (United States)

    Mwambete, Kennedy D; Tunzo, Jones; Justin-Temu, Mary

    2013-01-01

    This was a cross-sectional study intended to assess the prevalence and management of helminthiasis (HL) among underfives living with HIV/AIDS (ULHA). Clinical histories of ULHA were scrutinized for HIV/AIDS status, antiretroviral therapy (ART), HL prevalence, and their management. About 364 ULHA were studied, 213 (58.5%) were girls and 151 (41.5%) were boys. Of the 364 ULHA, 171 (47.5%) had HL and 64.3% were treated with albendazole (ABZ). Trichuriasis was ascribed to 23.6% of HL. Majority (72.5%) of ULHA had a CD4 count below 200 cells/mm³. Direct association was observed between CD4 counts and HL. About 55% ULHA were on lamivudine (3TC)-stavudine (d4T)-nevirapine (NVP; LSN) combination therapy. The ABZ-LSN combination was frequently used for HIV/AIDS and HL management. High prevalence of HL and vivid correlation between HIV status and HL were observed. The LSN-ABZ combination was frequently employed for management of HIV/AIDS and HL. We recommended prompt diagnosis of HL to avoid acceleration of HIV infection to AIDS.

  18. Prophylactic treatment of migraine; the patient's view, a qualitative study

    Directory of Open Access Journals (Sweden)

    Dekker Frans

    2012-03-01

    Full Text Available Abstract Background Prophylactic treatment is an important but under-utilised option for the management of migraine. Patients and physicians appear to have reservations about initiating this treatment option. This paper explores the opinions, motives and expectations of patients regarding prophylactic migraine therapy. Methods A qualitative focus group study in general practice in the Netherlands with twenty patients recruited from urban and rural general practices. Three focus group meetings were held with 6-7 migraine patients per group (2 female and 1 male group. All participants were migraine patients according to the IHS (International Headache Society; 9 had experience with prophylactic medication. The focus group meetings were analysed using a general thematic analysis. Results For patients several distinguished factors count when making a decision on prophylactic treatment. The decision of a patient on prophylactic medication is depending on experience and perspectives, grouped into five categories, namely the context of being active or passive in taking the initiative to start prophylaxis; assessing the advantages and disadvantages of prophylaxis; satisfaction with current migraine treatment; the relationship with the physician and the feeling to be heard; and previous steps taken to prevent migraine. Conclusion In addition to the functional impact of migraine, the decision to start prophylaxis is based on a complex of considerations from the patient's perspective (e.g. perceived burden of migraine, expected benefits or disadvantages, interaction with relatives, colleagues and physician. Therefore, when advising migraine patients about prophylaxis, their opinions should be taken into account. Patients need to be open to advice and information and intervention have to be offered at an appropriate moment in the course of migraine.

  19. Perceptions of Prophylactic Mastectomy in Korea

    Directory of Open Access Journals (Sweden)

    Han Young Yoon

    2016-01-01

    Full Text Available BackgroundIncreasingly, prophylactic mastectomy has been evaluated as a treatment of breast cancer. Hereditary breast cancer now accounts for approximately 5%–10% of all cases of breast cancer, meaning that the widespread implementation of prophylactic mastectomy may significantly reduce the occurrence of breast cancer. However, prophylactic mastectomy is rarely performed in Korea. Therefore, in this study, we assessed Koreans' attitudes toward and awareness of preventive mastectomy.MethodsThis was a prospective study of a cohort of patients attending outpatient clinics and their relatives. Data were collected using self-administered questionnaires assessing sex, age, educational level, knowledge of breast cancer, understanding of prophylactic mastectomy, attitudes toward prophylactic mastectomy, and reasons for choosing prophylactic mastectomy.ResultsSixty-five patients were included. Most patients (36.9% were between 40 and 49 years of age and 58.4% were college graduates. Only six respondents (9% understood prophylactic mastectomy, and 17 respondents (27% stated that they would agree to undergo prophylactic mastectomy if necessary. Reasons given for refusing prophylactic mastectomy included aesthetic concerns (38%, the perception that it would not cure the disease (26%, possible surgical complications (24%, and financial cost (6%.ConclusionsIn this study, most of the respondents showed a poor knowledge of prophylactic mastectomy. Ultimately, it will be necessary to establish medical guidelines for patients with a high risk of breast cancer, with the objective of providing accurate information and proper treatment at hospitals.

  20. Determinants of knowledge gain in evidence-based medicine short courses: an international assessment

    DEFF Research Database (Denmark)

    Witt, Klaus; Kunz, Regina; Wegscheider, Karl

    2010-01-01

    Background: Health care professionals worldwide attend courses and workshops to learn evidence-based medicine (EBM), but evidence regarding the impact of these educational interventions is conflicting and of low methodologic quality and lacks generalizability. Furthermore, little is known about...... determinants of success. We sought to measure the effect of EBM short courses and workshops on knowledge and to identify course and learner characteristics associated with knowledge acquisition. Methods: Health care professionals with varying expertise in EBM participated in an international, multicentre...... before–after study. The intervention consisted of short courses and workshops on EBM offered in diverse settings, formats and intensities. The primary outcome measure was the score on the Berlin Questionnaire, a validated instrument measuring EBM knowledge that the participants completed before and after...

  1. Watershed Management in Arid Zones: A Prototype Short Course.

    Science.gov (United States)

    Thames, John L., Ed.; Fischer, John N., Ed.

    Presented is information recommended for inclusion in a short course to help extend knowledge of water resource development and research techniques in arid and semi-arid regions. Information is particularly intended for applicability in developing nations. Included are considerations of livestock grazing, use of hydrologic data, vegetation…

  2. Integrating prevention of mother-to-child HIV transmission programs to improve uptake: a systematic review.

    Directory of Open Access Journals (Sweden)

    Lorainne Tudor Car

    Full Text Available BACKGROUND: We performed a systematic review to assess the effect of integrated perinatal prevention of mother-to-child transmission of HIV interventions compared to non- or partially integrated services on the uptake in low- and middle-income countries. METHODS: We searched for experimental, quasi-experimental and controlled observational studies in any language from 21 databases and grey literature sources. RESULTS: Out of 28 654 citations retrieved, five studies met our inclusion criteria. A cluster randomized controlled trial reported higher probability of nevirapine uptake at the labor wards implementing HIV testing and structured nevirapine adherence assessment (RRR 1.37, bootstrapped 95% CI, 1.04-1.77. A stepped wedge design study showed marked improvement in antiretroviral therapy (ART enrolment (44.4% versus 25.3%, p<0.001 and initiation (32.9% versus 14.4%, p<0.001 in integrated care, but the median gestational age of ART initiation (27.1 versus 27.7 weeks, p = 0.4, ART duration (10.8 versus 10.0 weeks, p = 0.3 or 90 days ART retention (87.8% versus 91.3%, p = 0.3 did not differ significantly. A cohort study reported no significant difference either in the ART coverage (55% versus 48% versus 47%, p = 0.29 or eight weeks of ART duration before the delivery (50% versus 42% versus 52%; p = 0.96 between integrated, proximal and distal partially integrated care. Two before and after studies assessed the impact of integration on HIV testing uptake in antenatal care. The first study reported that significantly more women received information on PMTCT (92% versus 77%, p<0.001, were tested (76% versus 62%, p<0.001 and learned their HIV status (66% versus 55%, p<0.001 after integration. The second study also reported significant increase in HIV testing uptake after integration (98.8% versus 52.6%, p<0.001. CONCLUSION: Limited, non-generalizable evidence supports the effectiveness of integrated PMTCT programs. More research measuring coverage and

  3. Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.

    Directory of Open Access Journals (Sweden)

    Anna Figueiredo

    2006-11-01

    Full Text Available Nonnucleoside reverse transcriptase inhibitors (NNRTIs target HIV-1 reverse transcriptase (RT by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. However, the consequences of this chemical enhancement effect on HIV-1 replication are not understood. Here, we show that the potent NNRTIs efavirenz, TMC120, and TMC125, but not nevirapine or delavirdine, inhibit the late stages of HIV-1 replication. These potent NNRTIs enhanced the intracellular processing of Gag and Gag-Pol polyproteins, and this was associated with a decrease in viral particle production from HIV-1-transfected cells. The increased polyprotein processing is consistent with premature activation of the HIV-1 protease by NNRTI-enhanced Gag-Pol multimerization through the embedded RT sequence. These findings support the view that Gag-Pol multimerization is an important step in viral assembly and demonstrate that regulation of Gag-Pol/Gag-Pol interactions is a novel target for small molecule inhibitors of HIV-1 production. Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation.

  4. Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis

    Science.gov (United States)

    Konstantopoulos, Aris; Tan, Xiao Wei; Goh, Gwendoline Tze Wei; Saraswathi, Padmanabhan; Chen, Liyan; Nyein, Chan Lwin; Zhou, Lei; Beuerman, Roger; Tan, Donald Tiang Hwee; Mehta, Jod

    2015-01-01

    prophylactic drops. Conclusions Prophylactic vancomycin drops provided short-term benefit, but did not prevent infection. Achieving MIC in the cornea was not sufficient to prevent Staphylococcus aureus keratitis. Patients should continue to be counselled regarding the risk of infection following keratoprosthesis. PMID:26460791

  5. Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.

    Directory of Open Access Journals (Sweden)

    Aris Konstantopoulos

    Full Text Available Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2-17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model.Twenty-three rabbits were assigned either to a prophylactic group (n = 13 that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10 that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7-12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP, anterior segment optical coherence tomography (AS-OCT, and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits.On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively. On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71 on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml exceeded minimum inhibitory concentration (MIC for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of prophylactic drops.Prophylactic

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    , nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation.......58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1......OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between...

  7. Isoniazid prophylactic therapy for tuberculosis in HIV-seropositive ...

    African Journals Online (AJOL)

    hypothetical cohort of 100 000 HIV-seropositive people in. South Africa over a ... health sector resources can be utilised in an optimal manner. This article ... second part we estimate the costs and benefits of isoniazid preventive ... The cohort was stratified into ... population risk of dying from any cause, the number of dual.

  8. Quality of life among dots (directly observed treatment short course ...

    African Journals Online (AJOL)

    Quality of life among dots (directly observed treatment short course) cured patients: ... which is a specific instrument and covers four domains of health i.e. physical, ... thereby necessitating measures for the improvement of the overall health of ...

  9. Modelling the Course of an HIV Infection: Insights from Ecology and Evolution

    Directory of Open Access Journals (Sweden)

    Carsten Magnus

    2012-10-01

    Full Text Available The Human Immunodeficiency Virus (HIV is one of the most threatening viral agents. This virus infects approximately 33 million people, many of whom are unaware of their status because, except for flu-like symptoms right at the beginning of the infection during the acute phase, the disease progresses more or less symptom-free for 5 to 10 years. During this asymptomatic phase, the virus slowly destroys the immune system until the onset of AIDS when opportunistic infections like pneumonia or Kaposi’s sarcoma can overcome immune defenses. Mathematical models have played a decisive role in estimating important parameters (e.g., virion clearance rate or life-span of infected cells. However, most models only account for the acute and asymptomatic latency phase and cannot explain the progression to AIDS. Models that account for the whole course of the infection rely on different hypotheses to explain the progression to AIDS. The aim of this study is to review these models, present their technical approaches and discuss the robustness of their biological hypotheses. Among the few models capturing all three phases of an HIV infection, we can distinguish between those that mainly rely on population dynamics and those that involve virus evolution. Overall, the modeling quest to capture the dynamics of an HIV infection has improved our understanding of the progression to AIDS but, more generally, it has also led to the insight that population dynamics and evolutionary processes can be necessary to explain the course of an infection.

  10. Survival of HIV/AIDS patients with antiretroviral therapy in association with first-line regimens from 2007 – 2010 in Haji AdamMalik general hospital Medan

    Science.gov (United States)

    Kembaren, T.; Ginting, Y.; Saragih, R. H.

    2018-03-01

    The mortality related to AIDS have decreased dramatically among HIV infected patients taking HAART. HAART is the combination of at least 3 antiretroviral drugs based on the recommendation of WHO. The recent guideline for 1st line therapy recommended by the Indonesian Ministry of Health was Zidovudine/Lamivudine/Nevirapine (ZDV+3TC+NVP), Zidovudine/Lamivudine/Efavirenz (ZDV+3TC+EFV), Stavudine/Lamivudine/Nevirapine (d4T+3TC+NVP), Stavudine/Lamivudine/Efavirenz (d4T+3TC+EFV). Due to a side effect of Stavudine, Ministry of Health plan to pass out Stavudin from the regimens for 1stline therapy.We wanted to evaluate the survival of HIV/AIDS patients with first-line regimens in HAM general hospital Medan. A cohort retrospective study was conducted to evaluate the survival of HIV/AIDS patients taking a combination of 1st line antiretroviral therapy between January 2007 and December 2010. From 2007-2010, among 609 HIV/AIDS patients with first-line ARV medication, 77.5% were male, and 22.5% were female. The most common risk infection was heterosexual. The majority of the patients were in 25-34 years old group. Most of the patients with CD4 1-50 cell/mm3. 2 years survival rate in HIV/AIDS patients taking ZDV+3TC+NVP, ZDV+3TC+EFV, d4T+3TC+NVP, d4T+3TC+EFV were 61.5%, 61.2%, 57.5% and 59.3% respectively. There were no significant differences of 24 months survival in both regiment with or without d4T, 61.8% vs 63.6%.

  11. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice.

    Science.gov (United States)

    Wu, Xilin; Guo, Jia; Niu, Mengyue; An, Minghui; Liu, Li; Wang, Hui; Jin, Xia; Zhang, Qi; Lam, Ka Shing; Wu, Tongjin; Wang, Hua; Wang, Qian; Du, Yanhua; Li, Jingjing; Cheng, Lin; Tang, Hang Ying; Shang, Hong; Zhang, Linqi; Zhou, Paul; Chen, Zhiwei

    2018-04-23

    The discovery of an HIV-1 cure remains a medical challenge because the virus rebounds quickly after the cessation of combination antiretroviral therapy (cART). Here, we investigate the potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb) as an innovative product for HIV-1 prophylactic and therapeutic interventions. We discovered that by preserving 2 single-chain variable fragment (scFv) binding domains of each parental bnAb, a single gene-encoded tandem bs-bnAb, BiIA-SG, displayed substantially improved breadth and potency. BiIA-SG neutralized all 124 HIV-1-pseudotyped viruses tested, including global subtypes/recombinant forms, transmitted/founder viruses, variants not susceptible to parental bnAbs and to many other bnAbs with an average IC50 value of 0.073 μg/ml (range HIV-1 stains. Moreover, whereas BiIA-SG delayed viral rebound in a short-term therapeutic setting when combined with cART, a single injection of adeno-associated virus-transferred (AAV-transferred) BiIA-SG gene resulted dose-dependently in prolonged in vivo expression of BiIA-SG, which was associated with complete viremia control and subsequent elimination of infected cells in humanized mice. These results warrant the clinical development of BiIA-SG as a promising bs-bnAb-based biomedical intervention for the prevention and treatment of HIV-1 infection.

  12. Determinants of virological outcome and adverse events in African children treated with paediatric nevirapine fixed-dose-combination tablets

    NARCIS (Netherlands)

    Bienczak, A.; Denti, P.; Cook, A.; Wiesner, L.; Mulenga, V.; Kityo, C.; Kekitiinwa, A.; Gibb, D.M.; Burger, D.M.; Walker, A.S.; McIlleron, H.

    2017-01-01

    BACKGROUND: Nevirapine is the only nonnucleoside reverse transcriptase inhibitor currently available as a paediatric fixed-dose-combination tablet and is widely used in African children. Nonetheless, the number of investigations into pharmacokinetic determinants of virological suppression in African

  13. Possible hepatotoxic consequence of nevirapine use in juvenile albino rats

    Directory of Open Access Journals (Sweden)

    Elias Adikwu

    2017-08-01

    Full Text Available Context: Nevirapine (NVP is used in human immunodeficiency virus exposed neonates. This could present safety concern due to decreased liver metabolizing enzymes activity and renal clearance in neonates. Aims: To determine the hepatotoxic effect of NVP in juvenile albino rats. Methods: Juvenile albino rats were weighed, divided into groups and treated orally with 4-32 mg/kg/day of NVP for 14 days including a recovery group. The control groups were treated with water (placebo and normal saline (solvent. At the end of NVP treatment, rats were weighed and sacrificed, blood was collected and serum extracted. Serum was analyzed for alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, total bilirubin (TB and conjugated bilirubin (CB. The liver was harvested via dissection, weighed and evaluated for AST, ALT, ALP, superoxide dismutase (SOD, catalase (CAT, glutathione (GSH, malondialdehyde (MDA levels and histological damage. Results: The body, absolute and relative liver weights of rats in NVP treated groups were not significantly different (p>0.05 when compared to placebo. However, serum levels of AST, ALT, ALP, TB and CB were significantly increased (p<0.05 in a dose-dependent manner in NVP-treated groups. Furthermore, liver levels of ALT, ALP, AST and MDA were significantly increased (p<0.05 while SOD, CAT, and GSH were decreased in a dose dependent manner in NVP-treated groups. NVP-treated rats were characterized by varying degrees of hepatic morphological alterations. However, in the recovery group, the effects of NVP were reversed. Conclusions: This study observed dose-dependent and reversible hepatotoxicity in nevirapine- treated juvenile albino rats.

  14. Short-course palliative radiotherapy for uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Hyun; Lee, Ju Hye; Ki, Yong Kan; Kim, Won Taek; Park, Dahl; Kim, Dong Won [Dept. of Radiation Oncology, Biomedical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of); Nam, Ji Ho; Jeon, Sang Ho [Dept. of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2013-12-15

    The purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer. Seventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions. The median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity. Short-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.

  15. Short-course palliative radiotherapy for uterine cervical cancer

    International Nuclear Information System (INIS)

    Kim, Dong Hyun; Lee, Ju Hye; Ki, Yong Kan; Kim, Won Taek; Park, Dahl; Kim, Dong Won; Nam, Ji Ho; Jeon, Sang Ho

    2013-01-01

    The purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer. Seventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions. The median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity. Short-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.

  16. Experience in presenting short courses in waste management technologies for secondary science and mathematics teachers

    International Nuclear Information System (INIS)

    Toth, W.J.; Smith, T.H.; Garcia, M.M.; Ferguson, J.E.

    1991-01-01

    The Department of Energy (DOE) and its Idaho National Engineering Laboratory (INEL) are developing educational programs that will help avert projected shortages in scientific and engineering manpower. One approach to this end is to help teachers become better prepared to teach topics that enthuse more students. INEL developed and offered a Short Course in Waste Management Technologies for Secondary Science and Mathematics Teachers. Short Course has two purposes: (1) to provide secondary-level science and mathematics teachers with training and information that will be useful to them in the classroom, and (2) to provide information on a topic of widespread interest in today's society, i.e., the management of hazardous and radioactive wastes and the restoration and preservation of the environment. This paper describes the development of the Short Course and summarizes some of the lessons learned in the preparation and presentation of such courses. 2 refs., 2 tabs

  17. Current status of prophylactic surgical treatment for familial adenomatous polyposis in Japan.

    Science.gov (United States)

    Yamadera, Masato; Ueno, Hideki; Kobayashi, Hirotoshi; Konishi, Tsuyoshi; Ishida, Fumio; Yamaguchi, Tatsuro; Hinoi, Takao; Inoue, Yasuhiro; Kanemitsu, Yukihide; Tomita, Naohiro; Ishida, Hideyuki; Sugihara, Kenichi

    2017-06-01

    We conducted this study to clarify the current clinical practice of prophylactic colectomy for patients with familial adenomatous polyposis (FAP) in Japan. This retrospective multi-center cohort study involved 23 specialized institutions for colorectal disease in Japan. We analyzed the records of 147 patients who underwent prophylactic surgical treatment between 2000 and 2012. Patients were divided into Group 1 (2000-2006) and Group 2 (2007-2012) based on their date of surgery. Age at the time of prophylactic surgery was 27 and 31 years in Groups 1 and 2, respectively. The proportion of attenuated FAP was significantly lower in Group 2 than in Group 1 (1.0 vs. 13 %, respectively). Pathological examination revealed an increased incidence of malignant polyps in the resected specimens from Group 2 patients (10 vs. 23 %, respectively; P = 0.034). Laparoscopic surgery was more frequent in Group 2 than in Group 1 (61 vs. 40 %, respectively). There was no surgical mortality in either group. Prophylactic surgery for FAP results in good short-term surgical outcomes in Japan. The current surgical approach is characterized by limited surgical indications for patients with attenuated FAP, delayed timing of colectomy, and the increasing standardization of laparoscopic surgery.

  18. The Evolution of Inquiry Activities in the Akamai Observatory Short Course, 2004-2009

    Science.gov (United States)

    Rice, E. L.; McElwain, M.; Sonnett, S.; Rafelski, M.

    2010-12-01

    The Akamai Observatory Short Course (AOSC) is a five-day course of activities designed to prepare college students majoring in science, technology, engineering, and mathematics (STEM) fields for internships at observatories on the Big Island of Hawai'i. The design and implementation of inquiry-based activities in the AOSC have evolved considerably over the six years of the course. The content goals have always focused on the basic understanding of light and optics necessary to understand telescopes, but the scientific process goals gradually evolved to reflect the increasingly recognized importance of engineering design skills for successful observatory internships. In 2004 the inquiry-based activities were limited to one well-established Color, Light, and Spectra activity. In subsequent years more activities were customized and expanded upon to reflect the learners' diverse academic backgrounds, the developing goals of the short course, and feedback from internship hosts. The most recent inquiry, the Design and Build a Telescope activity, engaged students in designing and building a simple telescope, emphasizing science and engineering process skills in addition to science content. This activity was influenced by the Mission Design activity, added in 2006, that incorporated the application of inquiry-based learning to the engineering design process and allowed students to draw upon their diverse prior knowledge and experience. In this paper we describe the inquiry-based activities in the AOSC in the context of its year-to-year evolution, including the conceptual and pragmatic changes to the short course that influenced the evolution.

  19. A window into a public program for prevention of mother to child transmission of HIV: Evidence from a prospective clinical trial

    Directory of Open Access Journals (Sweden)

    M Cotton

    2009-12-01

    Full Text Available Objectives To evaluate efficacy of the antenatal, intra-partum and post-natal antiretroviral components of a public service Prevention of Mother to Child (MTCT program in infants. Design Analysis of prospectively collected screening data of demographic and MTCT-related interventions and HIV-infection status of infants identified through HIV-specific DNA polymerase chain reaction. Setting Tygerberg Children’s Hospital, Western Cape Province, South Africa. Subjects HIV-infected women and their infants identified through participation in a public service MTCT program were referred for possible participation in a prospective study of isoniazid prophylaxis. Interventions Key components of the Program include voluntary counselling and testing, zidovudine to the mother from between 28 and 34 weeks gestation and to the newborn infant for the first week, single dose nevirapine to the mother in labour and the newborn shortly after birth and free formula for 6 months. Main Outcome Measures Number and percentage of HIV-infected infants and extent of exposure to antenatal, intrapartum and post-natal antiretrovirals. Results Of 656 infants with a median age of 12.6 weeks, screened between April 1st 2005 through May 2006, 39 were HIV-infected giving a transmission rate of 5.9% (95% CI: 4.4% - 8.0%. Antenatal prophylaxis was significantly associated with reduced transmission (OR: 0.43 (95% CI: 0.21 - 0.94 as opposed to intrapartum and postpartum components (p=0.85 and p=0.84, respectively. In multivariable analysis the antenatal component remained significant (OR=0.40 (95% CI 0.19 - 0.90. Conclusions The antenatal phase is the most important antiretroviral component of the MTCT program, allowing most opportunity for intervention.

  20. Difference-based clustering of short time-course microarray data with replicates

    Directory of Open Access Journals (Sweden)

    Kim Jihoon

    2007-07-01

    Full Text Available Abstract Background There are some limitations associated with conventional clustering methods for short time-course gene expression data. The current algorithms require prior domain knowledge and do not incorporate information from replicates. Moreover, the results are not always easy to interpret biologically. Results We propose a novel algorithm for identifying a subset of genes sharing a significant temporal expression pattern when replicates are used. Our algorithm requires no prior knowledge, instead relying on an observed statistic which is based on the first and second order differences between adjacent time-points. Here, a pattern is predefined as the sequence of symbols indicating direction and the rate of change between time-points, and each gene is assigned to a cluster whose members share a similar pattern. We evaluated the performance of our algorithm to those of K-means, Self-Organizing Map and the Short Time-series Expression Miner methods. Conclusions Assessments using simulated and real data show that our method outperformed aforementioned algorithms. Our approach is an appropriate solution for clustering short time-course microarray data with replicates.

  1. Modeling Outcomes of First-Line Antiretroviral Therapy and Rate of CD4 Counts Change among a Cohort of HIV/AIDS Patients in Ethiopia: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Tadesse Awoke

    Full Text Available Antiretroviral therapy has shown to be effective in reducing morbidity and mortality in patients infected with HIV for the past couples of decades. However, there remains a need to better understand the characteristics of long-term treatment outcomes in resource poor settings. The main aim of this study was to determine and compare the long-term response of patients on nevirapine and efavirenz based first line antiretroviral therapy regimen in Ethiopia.Hospital based retrospective cohort study was conducted from January 2009 to December 2013 at University hospital located in Northwest Ethiopia. Human subject research approval for this study was received from University of Gondar Research Ethics Committee and the medical director of the hospital. Cox-proportional hazards model was used to assess the effect of baseline covariates on composite outcome and a semi-parametric mixed effect model was used to investigate CD4 counts response to treatments.A total of 2386 HIV/AIDS naive patients were included in this study. Nearly one-in-four patients experienced the events, of which death, lost to follow up, treatment substitution and discontinuation of Non-Nucleoside Reverse Transcriptase Inhibitors(NNRTI accounted: 99 (26.8%, 122 (33.0%, 137 (37.0% and 12 (3.2%, respectively. The hazard of composite outcome on nevirapine compared with efavirenz was 1.02(95%CI: 0.52-1.99 with p-value = 0.96. Similarly, the hazard of composite outcome on tenofovir and stavudine compared with zidovudine were 1.87 (95%CI: 1.52-2.32, p-value < 0.0001 and 1.72(95% CI: 1.22-2.32, p-value = 0.002, respectively. The rate of CD4 increase in response to treatment was high during the first 10 months and stabilized later.This study revealed that treatment responses were comparable whether nevirapine or efavirenz was chosen to initiate antiretroviral therapy for HIV/AIDS patients in Ethiopia. There was significant difference on risk of composite outcome between patients who were

  2. Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies.

    Science.gov (United States)

    Hamers, Raph L; Sigaloff, Kim C E; Wensing, Annemarie M; Wallis, Carole L; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E; Wellington, Maureen; Osibogun, Akin; Stevens, Wendy S; Rinke de Wit, Tobias F; Schuurman, Rob

    2012-06-01

    Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy (ART). This cohort study examined patterns of drug-resistance mutations (DRMs) in individuals with virological failure on first-line ART at 13 clinical sites in 6 African countries and predicted their impact on second-line drug susceptibility. A total of 2588 antiretroviral-naive individuals initiated ART consisting of different nucleoside reverse transcriptase inhibitor (NRTI) backbones (zidovudine, stavudine, tenofovir, or abacavir, plus lamivudine or emtricitabine) with either efavirenz or nevirapine. Population sequencing after 12 months of ART was retrospectively performed if HIV RNA was >1000 copies/mL. The 2010 International Antiviral Society-USA list was used to score major DRMs. The Stanford algorithm was used to predict drug susceptibility. HIV-1 sequences were generated for 142 participants who virologically failed ART, of whom 70% carried ≥1 DRM and 49% had dual-class resistance, with an average of 2.4 DRMs per sequence (range, 1-8). The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A (14.1%). Thymidine analogue mutations were present in 8.5%. K65R was frequently selected by stavudine (15.0%) or tenofovir (27.7%). Among participants with ≥1 DRM, HIV-1 susceptibility was reduced in 93% for efavirenz/nevirapine, in 81% for lamivudine/emtricitabine, in 59% for etravirine/rilpivirine, in 27% for tenofovir, in 18% for stavudine, and in 10% for zidovudine. Early failure detection limited the accumulation of resistance. After stavudine failure in African populations, zidovudine rather than tenofovir may be preferred in second-line ART. Strategies to prevent HIV-1 resistance are a global priority.

  3. Leading Short-Term Study Abroad Courses: Motivations and Outcomes for Community College Faculty

    Science.gov (United States)

    Hull, Melinda Leigh

    2013-01-01

    This case study explored faculty motivations for choosing to lead short-term study abroad courses and the personal and professional outcomes of the undertaking as reported by the faculty members themselves. This study also identified specific instances of internationalized practice in the development and implementation of the course. Three faculty…

  4. Prophylactic belladonna suppositories on anesthetic recovery after robotic assisted laparoscopic prostatectomy.

    Science.gov (United States)

    Scavonetto, Federica; Lamborn, David R; McCaffrey, Joan M; Schroeder, Darrell R; Gettman, Mattew T; Sprung, Juraj; Weingarten, Toby N

    2013-06-01

    Two prospective trials have demonstrated prophylactic antimuscarinics following prostatectomy reduce pain from bladder spasms. Our practice adopted the routine administration of prophylactic belladonna and opium (B&O) suppositories to patients undergoing robotic assisted laparoscopic radical prostatectomy (RALP). The aim of this study is to determine if this change in clinical practice was associated with improvement of postoperative outcomes. The medical records of 202 patients that underwent RALP surgery who were or were not administered prophylactic B&O suppositories in the immediate postoperative period were abstracted for duration of anesthesia recovery, pain and analgesic use. Patient and surgical characteristics between groups were similar except B&O group were slightly older (p = 0.04) and administered less opioid analgesics (p = 0.05). There was no difference between groups in the duration of phase I recovery from anesthesia (p = 0.96). Multivariable adjustments for age, body mass index, American Society of Anesthesiologists physical status, and surgical duration were made, and again it was found that suppository administration had no association with phase I recovery times (p = 0.94). The use of antimuscarinic medication for bladder spams in the B&O group was less during phase I recovery (p suppositories at the immediate conclusion of RALP surgery was not associated with improvements of the postoperative course.

  5. Effectiveness of etravirine-based therapy for treatment-experienced HIV-infected patients.

    Science.gov (United States)

    Huerta García, Gloria; Mata-Marín, José Antonio; Domínguez-Hermosillo, Juan Carlos; Chavez-García, Marcelino; Banda-Lara, Marco Issac; Nuñez-Rodríguez, Nohemi; Cruz-Herrera, Javier Enrique; Sandoval-Ramírez, Jorge Luis; Villagómez-Ruiz, Alfredo; Manjarrez-Tellez, Bulmaro; Gaytan-Martínez, Jesús Enrique

    2016-06-30

    Treatment options are limited for HIV-1-infected individuals who have received extensive previous antiretroviral therapy. ETV has shown significant clinical benefits in treatment-experienced HIV-1+ patients with antiretroviral resistance. The aim of this study was to evaluate the effectiveness of ETV plus optimized background regimen in real-life conditions in a cohort of highly HIV-1 antiretroviral-experienced patients. Retrospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started therapy with an ETV-containing regimen. The effectiveness was evaluated using HIV-1 RNA viral load and changes in CD4+ cell count after 48 weeks of treatment. Forty-two patients ≥ 16 years of age were included; 74% were men, and the median age was 45 years (IQR 41-53). All participants had prior non-nucleoside reverse transcriptase inhibitor use (55% nevirapine, 83%, efavirenz, and 28% both). Baseline median HIV-1 RNA viral load was 15,598 copies/mL (IQR 2651-84,175) and CD4+ cell count was 276 cells/mL (IQR 155-436). After 48 weeks of treatment, 90.5% (95% CI 78-96) of patients had HIV-1 RNA viral load treatment to a median of 407 cells/mL (IQR 242-579); p HIV-1 RNA viral load ≥ 100,000 copies/mL (OR 7.6; 95% CI 1.2-44.80; p = 0.025). Our study provides clinically important evidence of the effectiveness and safety of ETV in highly antiretroviral-experienced HIV-1-infected patients.

  6. SPATIAL Short Courses Build Expertise and Community in Isotope Geochemistry

    Science.gov (United States)

    Riggs, E. M.; Bowen, G. J.

    2015-12-01

    The SPATIAL short course at the University of Utah is designed for graduate students and professionals in the earth and environmental sciences from around the globe. An integral part of the broader, NSF-funded Inter-university Training for Continental-scale Ecology (ITCE) project, the course is an intensive two-week field, classroom and laboratory experience with internationally-known researchers as instructors. The course focuses on stable isotope geochemistry coupled with spatial analysis techniques. Participants do not typically know each other or this research community well upon entering. One of the stated goals of the overall project is to build a community of practice around these techniques. This design is common in many professional fields, but is not often applied at the graduate level nor formally assessed in the earth sciences. Paired pre- and post-tests were administered before the start and after the close of the short courses over 3 years. The survey is a set of instruments adapted from social-cognitive psychology measuring changes in identity and community with other items to measure content knowledge outcomes. We see a subtle, consistent convergence of identities between large-scale isotope geochemistry and participants' research areas. Results also show that the course generates an increase in understanding about stable isotopes' use and application. The data show the SPATIAL course is very effective at bringing students together socially with each other and with faculty to create an environment that fosters community and scientific cooperation. Semi-structured pre-and post- interviews were conducted to understand the program elements that generated gains in learning and community. Participants were selected based on initial responses on the pre-survey to capture the range of initial conditions for the group. Qualitative analysis shows that the major factors for participants were 1) ready access to researchers in an informal setting during the

  7. Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands.

    Science.gov (United States)

    Sancineto, Luca; Iraci, Nunzio; Barreca, Maria Letizia; Massari, Serena; Manfroni, Giuseppe; Corazza, Gianmarco; Cecchetti, Violetta; Marcello, Alessandro; Daelemans, Dirk; Pannecouque, Christophe; Tabarrini, Oriana

    2014-09-01

    It is getting clearer that many drugs effective in different therapeutic areas act on multiple rather than single targets. The application of polypharmacology concepts might have numerous advantages especially for disease such as HIV/AIDS, where the rapid emergence of resistance requires a complex combination of more than one drug. In this paper, we have designed three hybrid molecules combining WM5, a quinolone derivative we previously identified as HIV Tat-mediated transcription (TMT) inhibitor, with the tricyclic core of nevirapine and BILR 355BS (BILR) non-nucleoside reverse transcriptase inhibitors (NNRTIs) to investigate whether it could be possible to obtain molecules acting on both transcription steps of the HIV replicative cycle. One among the three designed multiple ligands, reached this goal. Indeed, compound 1 inhibited both TMT and reverse transcriptase (RT) activity. Unexpectedly, while the anti-TMT activity exerted by compound 1 resulted into a selective inhibition of HIV-1 reactivation from latently infected OM10.1 cells, the anti-RT properties shown by all of the synthesized compounds did not translate into an anti-HIV activity in acutely infected cells. Thus, we have herein produced the proof of concept that the design of dual TMT-RT inhibitors is indeed possible, but optimization efforts are needed to obtain more potent derivatives. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. DYNAMICS OF THE ANXIETY DISORDERS IN THE COURSE OF SHORT-TERM PSYCHOTHERAPY

    Directory of Open Access Journals (Sweden)

    T.N. Hmylova

    2008-06-01

    Full Text Available The tendency of psychotherapy modern concepts referring to the short-term forms having been taken into account, we carried out the research aimed at the study of short-term form personality-oriented psychotherapy effect on the anxiety disorder dynamics. 103 patients with neurotic disorders were examined in the neurosis and psychotherapy department of the Bekhterev Psychoneurological Research Institute. The findings revealed the situational and personal anxiety level to be objectively decreased in the short-term group psychotherapy course. The short-term group psychotherapy was proved to bean effective method in anxiety disorders treatment considering indications and limitations.

  9. AIDS in the Third World: how to stop the HIV infection?

    Science.gov (United States)

    De Clercq, E

    2007-01-01

    Of the 38.6 million people living with HIV/AIDS globally, almost 25 million (65%) live in sub-Saharan Africa. Preventive strategies and measures fall short, often simply because they are not available or are largely male-controlled. A preventive HIV vaccine is still far away; hence the drive to develop alternative prevention technologies, such as microbicides and oral pre-exposure prophylaxis, that could be female controlled. There are, at present, twenty-two anti-HIV drugs which have been formally licensed for clinical use in the treatment of HIV infections (AIDS): zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir, nevirapine, delavirdine, efavirenz, saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir, darunavir and enfuvirtide. These compounds, in combination, form the basis of HAART (highly active antiretroviral therapy), which has led to the development of a single daily pill existing of the combination of tenofovir disoproxil fumarate, emtricitabine and efavirenz, which has to be taken orally once daily for the treatment of AIDS. Beyond development of new drugs and clinical evaluation of existing medications, several companies within the pharmaceutical industry have established innovative policies that provide HIV medications at affordable prices in the least-developed countries. Reduced pricing is not alone a solution, and thus companies are actively working in partnership with the World Health Organization and other multinational groups to address roadblocks such as complex registration and procurement systems. Even in this period of successful anti-HIV therapy via HAART, a growing number of patients is cycling through the various remaining therapeutic options and are increasingly becoming dependent of the availability of newly developed anti-HIV agents. It is of concern that existing and future therapies will have to be effective against newly evolving

  10. Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.

    Science.gov (United States)

    Fowler, Mary G; Qin, Min; Fiscus, Susan A; Currier, Judith S; Flynn, Patricia M; Chipato, Tsungai; McIntyre, James; Gnanashanmugam, Devasena; Siberry, George K; Coletti, Anne S; Taha, Taha E; Klingman, Karin L; Martinson, Francis E; Owor, Maxensia; Violari, Avy; Moodley, Dhayendre; Theron, Gerhard B; Bhosale, Ramesh; Bobat, Raziya; Chi, Benjamin H; Strehlau, Renate; Mlay, Pendo; Loftis, Amy J; Browning, Renee; Fenton, Terence; Purdue, Lynette; Basar, Michael; Shapiro, David E; Mofenson, Lynne M

    2016-11-03

    Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than

  11. Using Concept Maps to Teach a Nanotechnology Survey Short Course

    Science.gov (United States)

    Moyses, David D.; Rivet, Jennifer L.; Fahlman, Bradley D.

    2010-01-01

    We describe the use of concept maps within a 4-week nanotechnology survey course, designed for first-year undergraduate students. Because of the extremely short time frame of the class, students would be inundated with an overwhelming number of new concepts and definitions. Hence, we employed concept mapping to increase student retention and…

  12. Deterministic nonlinear systems a short course

    CERN Document Server

    Anishchenko, Vadim S; Strelkova, Galina I

    2014-01-01

    This text is a short yet complete course on nonlinear dynamics of deterministic systems. Conceived as a modular set of 15 concise lectures it reflects the many years of teaching experience by the authors. The lectures treat in turn the fundamental aspects of the theory of dynamical systems, aspects of stability and bifurcations, the theory of deterministic chaos and attractor dimensions, as well as the elements of the theory of Poincare recurrences.Particular attention is paid to the analysis of the generation of periodic, quasiperiodic and chaotic self-sustained oscillations and to the issue of synchronization in such systems.  This book is aimed at graduate students and non-specialist researchers with a background in physics, applied mathematics and engineering wishing to enter this exciting field of research.

  13. Prophylactic antibiotics and anticonvulsants in neurosurgery.

    Science.gov (United States)

    Ratilal, B; Sampaio, C

    2011-01-01

    The prophylactic administration of antibiotics to prevent infection and the prophylactic administration of anticonvulsants to prevent first seizure episodes are common practice in neurosurgery. If prophylactic medication therapy is not indicated, the patient not only incurs the discomfort and the inconvenience resulting from drug treatment but is also unnecessarily exposed to adverse drug reactions, and incurs extra costs. The main situations in which prophylactic anticonvulsants and antibiotics are used are described and those situations we found controversial in the literature and lack further investigation are identified: anticonvulsants for preventing seizures in patients with chronic subdural hematomas, antiepileptic drugs for preventing seizures in those suffering from brain tumors, antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures, and antibiotic prophylaxis for the surgical introduction of intracranial ventricular shunts.In the following we present systematic reviews of the literature in accordance with the standard protocol of The Cochrane Collaboration to evaluate the effectiveness of the use of these prophylactic medications in the situations mentioned. Our goal was to efficiently integrate valid information and provide a basis for rational decision-making.

  14. Regional differences in use of antiretroviral agents and primary prophylaxis in 3122 European HIV-infected patients. EuroSIDA Study Group

    DEFF Research Database (Denmark)

    Lundgren, Jens Dilling; Phillips, A N; Vella, S

    1997-01-01

    Little is known about how widely HIV-related drugs are used outside controlled clinical trials. We therefore assessed factors associated with use of antiretroviral (ARV) therapy and primary prophylactic regimens to prevent HIV-associated opportunistic infections. Baseline data from a prospective ...

  15. Rapid accumulation of HIV-1 thymidine analogue mutations and phenotypic impact following prolonged viral failure on zidovudine-based first-line ART in sub-Saharan Africa.

    Science.gov (United States)

    Goodall, Ruth L; Dunn, David T; Nkurunziza, Peter; Mugarura, Lincoln; Pattery, Theresa; Munderi, Paula; Kityo, Cissy; Gilks, Charles; Kaleebu, Pontiano; Pillay, Deenan; Gupta, Ravindra K

    2017-05-01

    Lack of viral load monitoring of ART is known to be associated with slower switch from a failing regimen and thereby higher prevalence of MDR HIV-1. Many countries have continued to use thymidine analogue drugs despite recommendations to use tenofovir in combination with a cytosine analogue and NNRTI as first-line ART. The effect of accumulated thymidine analogue mutations (TAMs) on phenotypic resistance over time has been poorly characterized in the African setting. A retrospective analysis of individuals with ongoing viral failure between weeks 48 and 96 in the NORA (Nevirapine OR Abacavir) study was conducted. We analysed 36 genotype pairs from weeks 48 and 96 of first-line ART (14 treated with zidovudine/lamivudine/nevirapine and 22 treated with zidovudine/lamivudine/abacavir). Phenotypic drug resistance was assessed using the Antivirogram assay (v. 2.5.01, Janssen Diagnostics). At 96 weeks, extensive TAMs (≥3 mutations) were present in 50% and 73% of nevirapine- and abacavir-treated patients, respectively. The mean (SE) number of TAMs accumulating between week 48 and week 96 was 1.50 (0.37) in nevirapine-treated participants and 1.82 (0.26) in abacavir-treated participants. Overall, zidovudine susceptibility of viruses was reduced between week 48 [geometric mean fold change (FC) 1.3] and week 96 (3.4, P  =   0.01). There was a small reduction in tenofovir susceptibility (FC 0.7 and 1.0, respectively, P  =   0.18). Ongoing viral failure with zidovudine-containing first-line ART is associated with rapidly increasing drug resistance that could be mitigated with effective viral load monitoring. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  16. The emerging profile of cross-resistance among the nonnucleoside HIV-1 reverse transcriptase inhibitors.

    Science.gov (United States)

    Sluis-Cremer, Nicolas

    2014-07-31

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are widely used to treat HIV-1-infected individuals; indeed most first-line antiretroviral therapies typically include one NNRTI in combination with two nucleoside analogs. In 2008, the next-generation NNRTI etravirine was approved for the treatment of HIV-infected antiretroviral therapy-experienced individuals, including those with prior NNRTI exposure. NNRTIs are also increasingly being included in strategies to prevent HIV-1 infection. For example: (1) nevirapine is used to prevent mother-to-child transmission; (2) the ASPIRE (MTN 020) study will test whether a vaginal ring containing dapivirine can prevent HIV-1 infection in women; (3) a microbicide gel formulation containing the urea-PETT derivative MIV-150 is in a phase I study to evaluate safety, pharmacokinetics, pharmacodynamics and acceptability; and (4) a long acting rilpivirine formulation is under-development for pre-exposure prophylaxis. Given their widespread use, particularly in resource-limited settings, as well as their low genetic barriers to resistance, there are concerns about overlapping resistance between the different NNRTIs. Consequently, a better understanding of the resistance and cross-resistance profiles among the NNRTI class is important for predicting response to treatment, and surveillance of transmitted drug-resistance.

  17. Clinical Course, Radiological Manifestations, and Outcome of Pneumocystis jirovecii Pneumonia in HIV Patients and Renal Transplant Recipients.

    Directory of Open Access Journals (Sweden)

    Lukas Ebner

    Full Text Available Pneumocystis jirovecii pneumonia (PCP is a frequent opportunistic infection in immunocompromised patients. In literature, presentation and outcome of PCP differs between patients with human immunodeficiency virus (HIV infection and renal transplant recipients (RTRs.We conducted a cross-sectional study of patients with PCP based on the HIV and renal transplant registries at our institution. Radiological and clinical data from all confirmed PCP cases between 2005 and 2012 were compared.Forty patients were included: 16 with HIV and 24 RTRs. Radiologically, HIV patients had significantly more areas of diffuse lung affection (81% HIV vs. 25% RTR; p = 0.02, more ground glass nodules 5-10 mm (69% vs. 4%; p = 80% in both groups. Duration from illness onset to hospital presentation was longer in the HIV patients (median of 18 vs. 10 days (p = 0.02, implying a less fulminant clinical course. Sixty percent of PCP cases in RTRs occurred >12 months after transplantation. Lengths of hospitalization, admission rates to the intensive care unit, and requirements for mechanical ventilation were similar. Outcome in both groups was favourable.While important differences in radiological presentation of PCP between HIV patients and RTRs were found, clinical presentation was similar. PCP only rarely presented with fulminant respiratory symptoms requiring ICU admission, with similar results and outcomes for HIV patients and RTRs. Early diagnosis and treatment is mandatory for clinical success.

  18. Prophylactic transabdominal amnioinfusion in oligohydramnios for preterm premature rupture of membranes: increase of amniotic fluid index during latency period.

    Science.gov (United States)

    Garzetti, G G; Ciavattini, A; De Cristofaro, F; La Marca, N; Arduini, D

    1997-01-01

    This study was designed to: (i) evaluate the effect of amnioinfusion on the latency period in patients with oligohydramnios for preterm premature rupture of membranes, and (ii) to investigate the relationship between changes in the amniotic fluid index and fetal heart rate short-term variability by computerized Hewlett-Packard cardiotocography, longitudinally estimated before and after prophylactic amnioinfusion. All singleton pregnancies with prolonged premature rupture of membranes after 25 weeks of gestation and seen at the Institute of Obstetrics and Gynecology, University of Ancona (Italy), between January 1994 and June 1995 were included in the study. Transabdominal amnioinfusion with 150-350 ml warmed normal saline (25-50 ml/min) was performed at weekly intervals. Amniotic fluid volume was assessed ultrasonographically by means of the four-quadrant technique on a weekly basis before and after each amnioinfusion, as well as the short-term variability by a Hewlett-Packard computerized cardiotocographic system. 18 women were enrolled and underwent prophylactic transabdominal amnioinfusion at weekly intervals until delivery. Eighteen controls, who did not undergo prophylactic amnioinfusion, were recruited from our 1992-1993 series and included in the study. The median interval between premature rupture of membranes and delivery was 3.0 weeks (range 1-8 weeks), with an average delivery age of 33.0 weeks (range 27-36 weeks). The latency period was significantly longer in patients who underwent prophylactic amnioinfusion (mean +/- SD, 4.1 +/- 1.7 weeks) than in controls(1.7 +/- 1.0 weeks; p amnioinfusion. A direct relationship was observed between the amniotic fluid index and short-term variability (linear regression analysis r = 0.54, p = 0.04). The mean values of fetal movements recorded by computerized tomography during the 20 min of observation significantly increased after amnioinfusion in comparison with those before it (2.6 +/- 0.9 and 0.9 +/- 0

  19. Guidelines for Developing Successful Short Advanced Courses in Systems Medicine and Systems Biology

    KAUST Repository

    Gomez-Cabrero, David

    2017-08-23

    Summary Systems medicine and systems biology have inherent educational challenges. These have largely been addressed either by providing new masters programs or by redesigning undergraduate programs. In contrast, short courses can respond to a different need: they can provide condensed updates for professionals across academia, the clinic, and industry. These courses have received less attention. Here, we share our experiences in developing and providing such courses to current and future leaders in systems biology and systems medicine. We present guidelines for how to reproduce our courses, and we offer suggestions for how to select students who will nurture an interdisciplinary learning environment and thrive there.

  20. Guidelines for Developing Successful Short Advanced Courses in Systems Medicine and Systems Biology

    KAUST Repository

    Gomez-Cabrero, David; Marabita, Francesco; Tarazona, Sonia; Cano, Isaac; Roca, Josep; Conesa, Ana; Sabatier, Philippe; Tegner, Jesper

    2017-01-01

    Summary Systems medicine and systems biology have inherent educational challenges. These have largely been addressed either by providing new masters programs or by redesigning undergraduate programs. In contrast, short courses can respond to a different need: they can provide condensed updates for professionals across academia, the clinic, and industry. These courses have received less attention. Here, we share our experiences in developing and providing such courses to current and future leaders in systems biology and systems medicine. We present guidelines for how to reproduce our courses, and we offer suggestions for how to select students who will nurture an interdisciplinary learning environment and thrive there.

  1. Prophylactic digitalisation in pulmonary surgery.

    Science.gov (United States)

    Ritchie, A J; Danton, M; Gibbons, J R

    1992-01-01

    Prophylactic digoxin is widely used in patients undergoing pulmonary surgery to prevent or control cardiac arrhythmias, but whether it is helpful or not is uncertain. An open, controlled randomised prospective clinical study of 111 patients was undertaken to compare the incidence of cardiac arrhythmias in the 58 patients who received preoperative digoxin and the 53 who did not. Cardiac arrhythmia occurred in half (29/58) of those given prophylactic digoxin and in 36% (19/53) of those who were not. The overall incidence of arrhythmia was 43%, with no statistically significant difference between the groups. Cardiac arrhythmias remain an important complication of pulmonary surgery and the incidence is not reduced by prophylactic digoxin.

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

    Science.gov (United States)

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

    2012-01-01

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

  3. Lifetime Costs of Prophylactic Mastectomies and Reconstruction versus Surveillance.

    Science.gov (United States)

    Mattos, David; Gfrerer, Lisa; Reish, Richard G; Hughes, Kevin S; Cetrulo, Curtis; Colwell, Amy S; Winograd, Jonathan M; Yaremchuk, Michael J; Austen, William G; Liao, Eric C

    2015-12-01

    The past decade has seen an increasing prevalence of prophylactic mastectomy with decreasing ages of patients treated for breast cancer. Data are limited on the fiscal impacts of contralateral prophylactic mastectomy trends, and no study has compared bilateral prophylactic mastectomy with reconstruction to surveillance in high-risk patients. Lifetime third-party payer costs over 30 years were estimated with 2013 Medicare reimbursement rates. Costs were estimated for patients choosing contralateral or bilateral prophylactic mastectomy versus surveillance, with immediate reconstructions using a single-stage implant, tissue expander, or perforator-based free flap approach. Published cancer incidence rates predicted the percentage of surveillance patients that would require mastectomies. Sensitivity analyses were conducted that varied cost growth, discount rate, cancer incidence rate, and other variables. Lifetime costs and present values (3 percent discount rate) were estimated. Lifetime prophylactic mastectomy costs were lower than surveillance costs, $1292 to $1993 lower for contralateral prophylactic mastectomy and $15,668 to $21,342 lower for bilateral prophylactic mastectomy, depending on the reconstruction. Present value estimates were slightly higher for contralateral prophylactic mastectomy over contralateral surveillance but still cost saving for bilateral prophylactic mastectomy compared with bilateral surveillance. Present value estimates are also cost saving for contralateral prophylactic mastectomy when the modeled contralateral breast cancer incidence rate is increased to at least 0.6 percent per year. These findings are consistent with contralateral and bilateral prophylactic mastectomy being cost saving in many scenarios, regardless of the reconstructive option chosen. They suggest that physicians and patients should continue to receive flexibility in deciding how best to proceed clinically in each case.

  4. Status of prophylactic and therapeutic genital herpes vaccines.

    Science.gov (United States)

    Awasthi, Sita; Friedman, Harvey M

    2014-06-01

    A half billion people have genital herpes infections worldwide. Approximately one-fifth of American women between ages 14 and 49 are HSV-2 seropositive. The development of an effective genital herpes vaccine is a global health necessity based on the mental anguish genital herpes causes for some individuals, the fact that pregnant women with genital herpes risk transmitting infection to their newborn children, and the observation that HSV-2 infection is associated with a 3-fold to 4-fold increased probability of HIV acquisition. We review the strengths and limitations of preclinical animal models used to assess genital herpes vaccine candidates and the goals of prophylactic and therapeutic vaccines. We also discuss the current pipeline of vaccine candidates and lessons learned from past clinical trials that serve as a stimulus for new strategies, study designs and endpoint determinations. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Review The Emerging Profile of Cross-Resistance among the Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors

    Directory of Open Access Journals (Sweden)

    Nicolas Sluis-Cremer

    2014-07-01

    Full Text Available Nonnucleoside reverse transcriptase inhibitors (NNRTIs are widely used to treat HIV-1-infected individuals; indeed most first-line antiretroviral therapies typically include one NNRTI in combination with two nucleoside analogs. In 2008, the next-generation NNRTI etravirine was approved for the treatment of HIV-infected antiretroviral therapy-experienced individuals, including those with prior NNRTI exposure. NNRTIs are also increasingly being included in strategies to prevent HIV-1 infection. For example: (1 nevirapine is used to prevent mother-to-child transmission; (2 the ASPIRE (MTN 020 study will test whether a vaginal ring containing dapivirine can prevent HIV-1 infection in women; (3 a microbicide gel formulation containing the urea-PETT derivative MIV-150 is in a phase I study to evaluate safety, pharmacokinetics, pharmacodynamics and acceptability; and (4 a long acting rilpivirine formulation is under-development for pre-exposure prophylaxis. Given their widespread use, particularly in resource-limited settings, as well as their low genetic barriers to resistance, there are concerns about overlapping resistance between the different NNRTIs. Consequently, a better understanding of the resistance and cross-resistance profiles among the NNRTI class is important for predicting response to treatment, and surveillance of transmitted drug-resistance.

  6. Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles

    DEFF Research Database (Denmark)

    Pavlos, Rebecca; McKinnon, Elizabeth J.; Ostrov, David A.

    2017-01-01

    Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is...

  7. Uptake and performance of prevention of mother-to-child transmission and early infant diagnosis in pregnant HIV-infected women and their exposed infants at seven health centres in Addis Ababa, Ethiopia.

    Science.gov (United States)

    Girma, Marshet; Wendaferash, Rahel; Shibru, Hailu; Berhane, Yemane; Hoelscher, Michael; Kroidl, Arne

    2017-06-01

    To assess the uptake of WHO-recommended PMTCT procedures in Ethiopia's health services. Prospective observational study of HIV-positive pregnant mothers and their newborns attending PMTCT services at seven health centres in Addis Ababa. Women were recruited during antenatal care and followed up with their newborns at delivery, Day 6 and Week 6 post-partum. Retention to PMCTC procedures, self-reported antiretroviral treatment (ART) adherence and HIV infant outcome were assessed. Turnaround times of HIV early infant diagnosis (EID) procedures were extracted from health registers. Of 494 women enrolled, 4.9% did not complete PMTCT procedures due to active denial or loss to follow-up. HIV was first diagnosed in 223 (45.1%) and ART initiated in 321 (65.0%) women during pregnancy. ART was initiated in a median of 1.3 weeks (IQR 0-4.3) after HIV diagnosis. Poor self-reported treatment adherence was higher post-partum than during pregnancy (12.5% vs. 7.0%, P = 0.002) and significantly associated with divorced/separated marital status (RR 2.2, 95% CI 1.3-3.8), low family income (RR 2.1, 95% CI 1.1-4.1), low CD4 count (RR 1.7, 95% CI 1.0-3.0) and ART initiation during delivery (RR 2.5, 95% CI 1.1-5.6). Of 435 infants born alive, 98.6% received nevirapine prophylaxis. The mother-to-child HIV transmission rate was 0.7% after a median of 6.7 weeks (IQR 6.4-10.4), but EID results were received for only 46.6% within 3 months of birth. High retention in PMTCT services, triple maternal ART and high infant nevirapine prophylaxis coverage were associated with low mother-to-child HIV transmission. Declining post-partum ART adherence and challenges of EID linkage require attention. © 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  8. Short report: migration among persons living with HIV.

    Science.gov (United States)

    Berk, Marc L; Schur, Claudia L; Dunbar, Jennifer L; Bozzette, Sam; Shapiro, Martin

    2003-09-01

    Data from the first national probability sample of persons with HIV, the HIV Cost of Services and Utilization Survey (HCSUS), are used to examine migration patterns among persons with HIV/AIDS in the USA. Persons with serious illness may choose to relocate to receive better care or support. This migration has implications for the distribution of resources. This study describes the frequency and reasons that persons with HIV move to different communities. An analytic file of 3014 respondents was obtained from the first national probability sample of persons with HIV/AIDS, the HCSUS. A migration section of the baseline questionnaire questioned respondents on their residential history. Persons were defined as movers if they moved across state lines or to a non-contiguous county after knowing they were HIV positive but before the HCSUS baseline interview. Forty percent of movers said that their HIV status was a very important factor in their decision to move. Although earlier studies of limited generalizability found movement among the HIV population from urban to rural counties, this study found only eight percent of HIV migration was from urban to rural counties, just slightly more than the migration from rural to urban counties. In addition, the vast majority of people who were moving were not moving to return home. Major factors in the decision to move included being near caregivers and being in a community with shared needs and interests. Significant numbers of persons also moved to obtain care from a physician knowledgeable in HIV treatment or to get away from discrimination. Financial assistance and the availability of Medicaid also played a prominent role in many decisions to move. Persons with HIV/AIDS are more likely to move than non-infected persons in the general population. Moreover, they are almost twice as likely to be moving out-of-state. Persons with HIV who move are similar to persons with HIV who do not move on most demographic characteristics

  9. Short-course TLR9 Agonist Treatment Impacts Innate Immunity and Plasma Viremia in Individuals with HIV infection

    DEFF Research Database (Denmark)

    Vibholm, Line; Schleimann, Mariane H; Højen, Jesper F

    2017-01-01

    Background.: Treatment with latency reversing agents (LRAs) enhances human immunodeficiency virus type 1 (HIV-1) transcription in vivo but leads to only modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized...... that a single drug molecule-a novel Toll-like receptor 9 (TLR9) agonist, MGN1703-could function as an enhancer of innate immunity and an LRA in vivo. Methods.: We conducted a single-arm, open-label study in which 15 virologically suppressed HIV-1-infected individuals on antiretroviral therapy received 60 mg MGN.......: In accordance with the cell type-specific expression of TLR9, MGN1703 treatment led to pronounced activation of plasmacytoid dendritic cells and substantial increases in plasma interferon-α2 levels (P

  10. Prophylactic treatment of retinal breaks

    DEFF Research Database (Denmark)

    Blindbæk, Søren Leer; Grauslund, Jakob

    2015-01-01

    Prophylactic treatment of retinal breaks has been examined in several studies and reviews, but so far, no studies have successfully applied a systematic approach. In the present systematic review, we examined the need of follow-up after posterior vitreous detachment (PVD) - diagnosed by slit...... published before 2012. Four levels of screening identified 13 studies suitable for inclusion in this systematic review. No meta-analysis was conducted as no data suitable for statistical analysis were identified. In total, the initial examination after symptomatic PVD identified 85-95% of subsequent retinal......-47% of cases, respectively. The cumulated incidence of RRD despite prophylactic treatment was 2.1-8.8%. The findings in this review suggest that follow-up after symptomatic PVD is only necessary in cases of incomplete retinal examination at presentation. Prophylactic treatment of symptomatic retinal breaks...

  11. Migration as a risk and a livelihood strategy: HIV across the life course of migrant families in India.

    Science.gov (United States)

    Rai, Tanvi; Lambert, Helen S; Ward, Helen

    2017-04-01

    Migrant workers are understood to be vulnerable to HIV. However, little is known about the experience of migration-based households following HIV infection. This qualitative study examined the migration-HIV relationship beyond the point of infection, looking at how it affects livelihood choices, household relationships and the economic viability of migrant families. We conducted semi-structured interviews with 33 HIV-positive migrant men and women recruited from an anti-retroviral therapy (ART) centre in north India. Following infection among the migrant men, contact with free, public-sector HIV services was often made late, after the development of debilitating symptoms, abandonment of migrant work and return to native villages. After enrolment at the ART centre participants' health eventually stabilised but they now faced serious economic debt, an inflexible treatment regimen and reduced physical strength. Insecure migrant job markets, monthly drug collection and discriminatory employment policies impeded future migration plans. HIV-positive wives of migrants occupied an insecure position in the rural marital household that depended on their husbands' health and presence of children. The migration-HIV relationship continued to shape the life course of migrant families beyond the point of infection, often exposing them again to the economic insecurity that migration had helped to overcome, threatening their long-term survival.

  12. Autologous saliva transfusion: treatment for HIV?

    Science.gov (United States)

    Arakeri, Gururaj

    2010-05-01

    The HIV-1 pandemic is a complex mix of diverse epidemics within and between countries and regions of the world, and is undoubtedly the defining public-health crisis of our time. Any therapeutic or prophylactic measure which holds promise or provides clues of eliminating or inhibiting the infection is worthy of investigation. As our body's own saliva is suspiciously escaping from the infection and providing clues regarding the resistance/inhibition of HIV; in this paper, a treatment approach is suggested with the rationale of in vitro effective antiviral action of autogenous saliva may also have a better therapeutic potential by its intravenous administration along with dextran.

  13. Early diagnosis of HIV in children below 18 months using DNA PCR test--assessment of the effectiveness of PMTCT interventions and challenges in early initiation of ART in a resource-limited setting.

    Science.gov (United States)

    Gupta, Anil; Singh, Girraj; Kaushik, Pratap; Joshi, Bipin; Kalra, Kamlesh; Chakraborty, Sabyasachi

    2013-04-01

    This study was conducted to assess efficacy of the current Indian Prevention of Mother-to-Child Transmission (PMTCT) protocol in 217 HIV-exposed infants, and to assess challenges in the early initiation of antiretroviral treatment (ART) in 18 (8.3%) infants with HIV, as determined by the HIV-1 DNA polymerase chain reaction (PCR) test at ≥ 6 weeks to ART was initiated in 10 (55.6%) HIV-infected children at a mean ± standard deviation (SD) age of 10.45 ± 4.9 (range: 4-17.5) months; delay resulted in opportunistic infections in one-third of the children. A single-dose nevirapine PMTCT regimen should be replaced by a triple antiretroviral regimen; DBS DNA PCR-positive infants may be given ART, and simultaneously a whole blood specimen should be taken to determine whether ART should be continued.

  14. Falling short of universal access to reproductive health: unintended pregnancy and contraceptive use among Mexican women with HIV.

    Science.gov (United States)

    Kendall, Tamil

    2013-01-01

    A favourable context for women with HIV to prevent unintended pregnancy is a cornerstone of reproductive rights and will contribute to achieving universal access to reproductive health, a Millennium Development Goal target. This analysis explores the reproductive trajectories of Mexican women with HIV post-diagnosis and their access to reproductive counselling and use of contraceptives. In-depth interviews and short surveys were conducted with women of reproductive age living with HIV. Results indicate that sexual and reproductive health counselling in HIV care focuses on the male condom and does not routinely address reproductive desires or provide information about or access to other contraceptive methods. Unintended pregnancies result from inconsistent condom use and condom breakage. Women experienced discriminatory denial of and pressure to accept particular contraceptive methods because of their HIV status. Mexican women with HIV are not enjoying their constitutionally guaranteed right to freely choose the number and spacing of their children. Mexico's commitment to reproductive rights and the Popular Health Insurance offer policy and financial frameworks for providing family planning services in public HIV clinics. To ensure respectful implementation, rights-based training for HIV healthcare providers and careful monitoring and evaluation will be needed.

  15. The effect of prophylactic antipyretic administration on post-vaccination adverse reactions and antibody response in children: a systematic review.

    Directory of Open Access Journals (Sweden)

    Rashmi Ranjan Das

    Full Text Available Prophylactic antipyretic administration decreases the post-vaccination adverse reactions. Recent study finds that they may also decrease the antibody responses to several vaccine antigens. This systematic review aimed to assess the evidence for a relationship between prophylactic antipyretic administration, post-vaccination adverse events, and antibody response in children.A systematic search of major databases including MEDLINE and EMBASE was carried out till March 2014. Randomized controlled trials (RCTs comparing prophylactic antipyretic treatment versus placebo post-vaccination in children ≤ 6 years of age were included. Two reviewers independently applied eligibility criteria, assessed the studies for methodological quality, and extracted data [PROSPERO registration: CRD42014009717].Of 2579 citations retrieved, a total of 13 RCTs including 5077 children were included in the review. Prophylactic antipyretic administration significantly reduced the febrile reactions (≥ 38.0 °C after primary and booster vaccinations. Though there were statistically significant differences in the antibody responses between the two groups, the prophylactic PCM group had what would be considered protective levels of antibodies to all of the antigens given after the primary and booster vaccinations. No significant difference in the nasopharyngeal carriage rates (short-term and long-term of H. influenzae or S. pneumoniae serotypes was found between the prophylactic and no prophylactic PCM group. There was a significant reduction in the local and systemic symptoms after primary, but not booster vaccinations.Though prophylactic antipyretic administration leads to relief of the local and systemic symptoms after primary vaccinations, there is a reduction in antibody responses to some vaccine antigens without any effect on the nasopharyngeal carriage rates of S. pneumoniae & H. influenza serotypes. Future trials and surveillance programs should also aim at

  16. Etravirine and Rilpivirine Drug Resistance Among HIV-1 Subtype C Infected Children Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in South India.

    Science.gov (United States)

    Saravanan, Shanmugam; Kausalya, Bagavathi; Gomathi, Selvamurthi; Sivamalar, Sathasivam; Pachamuthu, Balakrishnan; Selvamuthu, Poongulali; Pradeep, Amrose; Sunil, Solomon; Mothi, Sarvode N; Smith, Davey M; Kantor, Rami

    2017-06-01

    We have analyzed reverse transcriptase (RT) region of HIV-1 pol gene from 97 HIV-infected children who were identified as failing first-line therapy that included first-generation non-nucleoside RT inhibitors (Nevirapine and Efavirenz) for at least 6 months. We found that 54% and 65% of the children had genotypically predicted resistance to second-generation non-nucleoside RT inhibitors drugs Etravirine (ETR) and Rilpivirine, respectively. These cross-resistance mutations may compromise future NNRTI-based regimens, especially in resource-limited settings. To complement these investigations, we also analyzed the sequences in Stanford database, Monogram weighted score, and DUET weighted score algorithms for ETR susceptibility and found almost perfect agreement between the three algorithms in predicting ETR susceptibility from genotypic data.

  17. Serum lactate levels in infants exposed peripartum to antiretroviral agents to prevent mother-to-child transmission of HIV: Agence Nationale de Recherches Sur le SIDA et les Hépatites Virales 1209 study, Abidjan, Ivory Coast

    Science.gov (United States)

    Ekouevi, Didier Koumavi; Touré, Ramata; Becquet, Renaud; Viho, Ida; Sakarovitch, Charlotte; Rouet, François; Towne-Gold, Besigin; Fassinou, Patricia; Leroy, Valériane; Blanche, Stéphane; Dabis, François

    2006-01-01

    Background Mitochondrial toxicity was described in infants exposed to long-term antiretroviral regimens (ARVs) containing nucleoside analogues for the prevention of mother-to-child transmission of HIV (PMTCT). We measured the serum lactate levels in children born to HIV-1 infected (HIV+) African women receiving short-term ARV PMTCT regimens. Methods A prospective study was conducted in women-child pairs from the third trimester of pregnancy to three months of life. The exposed group was formed by children exposed in utero to nucleoside analogue ARVs, zidovudine (ZDV) or ZDV + lamivudine (3TC) from 32–36 weeks of amenorrhea until delivery. All these women received nevirapine single-dose (NVPsd) at the beginning of labor. The children received ZDV during the first 7 days of life and a NVPsd at day 3. The control group was formed by infants born to HIV+ women who had received NVPsd only and not exposed to nucleoside analogue ARVs. Serum lactate levels were measured at 4, 6 and 12 weeks of life by Cobas Integra 400™. Results A total of 836 blood samples from 338 infants were collected (262 exposed and 76 controls). Median lactacidemia was 1.8 mmol/l, Interquartile Range [1.2–2.7 mmol/l]). Overall serum lactate levels ≥2.5 mmol/l, defining hyperlactatemia were observed in 39 of the 292 infants who had at least two serum lactate measurements, 13.4%, 95% confidence Interval [9.6–17.8%]. The three-month period prevalence of hyperlactatemia did not differ between the exposed group (13.1%) and the control group (14.3%) (p=0.84). All serum lactate levels returned to normal values in all subsequent samples No case of symptomatic hyperlactatemia was detected during the study period. Conclusion Increased lactate levels were identified equally in infants whose mother received a short-term of nucleoside analogues or NVPsd for PMTCT. Although not rare, hyperlactatemia was not related to short-term exposure to nucleoside analogue ARVs PMID:16950945

  18. Effect of HIV-1 envelope cytoplasmic tail on adenovirus primed virus encoded virus-like particle immunizations

    DEFF Research Database (Denmark)

    Andersson, Anne Marie C; Ragonnaud, Emeline; Seaton, Kelly E.

    2016-01-01

    were found between the different priming regimens as both induced high titered tier 1 neutralizing antibodies, but no tier 2 antibodies, possibly reflecting the similar presentation of trimer specific antibody epitopes. The described vaccine regimens provide insight into the effects of the HIV-1 Env......The low number of envelope (Env) spikes presented on native HIV-1 particles is a major impediment for HIV-1 prophylactic vaccine development. We designed virus-like particle encoding adenoviral vectors utilizing SIVmac239 Gag as an anchor for full length and truncated HIV-1 M consensus Env...

  19. Pneumocystis jirovecii colonisation in HIV-positive and HIV-negative subjects in Cameroon.

    Science.gov (United States)

    Riebold, D; Enoh, D O; Kinge, T N; Akam, W; Bumah, M K; Russow, K; Klammt, S; Loebermann, M; Fritzsche, C; Eyong, J E; Eppel, G; Kundt, G; Hemmer, C J; Reisinger, E C

    2014-06-01

    To determine the prevalence of Pneumocystis pneumonia (PCP), a major opportunistic infection in AIDS patients in Europe and the USA, in Cameroon. Induced sputum samples from 237 patients without pulmonary symptoms (126 HIV-positive and 111 HIV-negative outpatients) treated at a regional hospital in Cameroon were examined for the prevalence of Pneumocystis jirovecii by specific nested polymerase chain reaction (nPCR) and staining methods. CD 4 counts and the history of antiretroviral therapy of the subjects were obtained through the ESOPE database system. Seventy-five of 237 study participants (31.6%) were colonised with Pneumocystis, but none showed active PCP. The Pneumocystis colonisation rate in HIV-positive subjects was more than double that of HIV-negative subjects (42.9% vs. 18.9%, P 500 cells/μl were colonised at a rate of 20.0%, subjects with CD 4 counts between 200 and 500 cells/μl of 42.5%, and subjects with CD 4 counts <200 cells/μl of 57.1%. Colonisation with Pneumocystis in Cameroon seems to be comparable to rates found in Western Europe. Prophylactic and therapeutic measures against Pneumocystis should be taken into account in HIV care in western Africa. © 2014 John Wiley & Sons Ltd.

  20. Association of pol diversity with antiretroviral treatment outcomes among HIV-infected African children.

    Directory of Open Access Journals (Sweden)

    Iris Chen

    Full Text Available In HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART. We measured HIV diversity in African children (ages 6-36 months enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial. Children in this cohort were exposed to single dose nevirapine (sdNVP at birth.HIV diversity was measured retrospectively using a high resolution melting (HRM diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in pol, and three in env. A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions.In multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity in pol (P = 0.005 and with higher mean (P = 0.014 and median (P<0.001 HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pre-treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016 and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P<0.001 for all measures.In this cohort of sdNVP-exposed, ART-naïve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes.

  1. Computer-Automated Approach for Scoring Short Essays in an Introductory Statistics Course

    Science.gov (United States)

    Zimmerman, Whitney Alicia; Kang, Hyun Bin; Kim, Kyung; Gao, Mengzhao; Johnson, Glenn; Clariana, Roy; Zhang, Fan

    2018-01-01

    Over two semesters short essay prompts were developed for use with the Graphical Interface for Knowledge Structure (GIKS), an automated essay scoring system. Participants were students in an undergraduate-level online introductory statistics course. The GIKS compares students' writing samples with an expert's to produce keyword occurrence and…

  2. Efficacy and safety of short course adjuvant trastuzumab combination chemotherapy in breast cancer

    Directory of Open Access Journals (Sweden)

    Sachin S Hingmire

    2017-01-01

    Full Text Available Background: The adjuvant short course 9-week trastuzumab combination therapy for human epidermal receptor 2 positive breast cancer patients may often be considered as a cost-effective and safe option and has important implications for the Indian subcontinent as well as other developing countries. However, such regimens of shorter duration trastuzumab therapy like FinHer, offered in view of economic constraints, may not be able to achieve globally comparable cure rates in early breast cancer especially with high-risk women with more than 3 lymph node positive. Methods and Material: Outcome of 21 patients with HER2 positive breast cancer was treated with short course trastuzumab combination chemotherapy in the adjuvant setting was studied. Results: Out of 21 patients 15 are alive and disease free with a follow up of up to 73 months (median follow up 42 months.

  3. An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors.

    Science.gov (United States)

    Pagano, Nicholas; Teriete, Peter; Mattmann, Margrith E; Yang, Li; Snyder, Beth A; Cai, Zhaohui; Heil, Marintha L; Cosford, Nicholas D P

    2017-12-01

    Continuous flow (microfluidic) chemistry was employed to prepare a small focused library of dihydropyrimidinone (DHPM) derivatives. Compounds in this class have been reported to exhibit activity against the human immunodeficiency virus (HIV), but their molecular target had not been identified. We tested the initial set of DHPMs in phenotypic assays providing a hit (1i) that inhibited the replication of the human immunodeficiency virus HIV in cells. Flow chemistry-driven optimization of 1i led to the identification of HIV replication inhibitors such as 1l with cellular potency comparable with the clinical drug nevirapine (NVP). Mechanism of action (MOA) studies using cellular and biochemical assays coupled with 3D fingerprinting and in silico modeling demonstrated that these drug-like probe compounds exert their effects by inhibiting the viral reverse transcriptase polymerase (RT). This led to the design and synthesis of the novel DHPM 1at that inhibits the replication of drug resistant strains of HIV. Our work demonstrates that combining flow chemistry-driven analogue refinement with phenotypic assays, in silico modeling and MOA studies is a highly effective strategy for hit-to-lead optimization applicable to the discovery of future therapeutic agents. Copyright © 2017. Published by Elsevier Ltd.

  4. Prophylactic treatment of vestibular migraine

    Directory of Open Access Journals (Sweden)

    Márcio Cavalcante Salmito

    Full Text Available Abstract Introduction: Vestibular migraine (VM is now accepted as a common cause of episodic vertigo. Treatment of VM involves two situations: the vestibular symptom attacks and the period between attacks. For the latter, some prophylaxis methods can be used. The current recommendation is to use the same prophylactic drugs used for migraines, including β-blockers, antidepressants and anticonvulsants. The recent diagnostic definition of vestibular migraine makes the number of studies on its treatment scarce. Objective: To evaluate the efficacy of prophylactic treatment used in patients from a VM outpatient clinic. Methods: Review of medical records from patients with VM according to the criteria of the Bárány Society/International Headache Society of 2012 criteria. The drugs used in the treatment and treatment response obtained through the visual analog scale (VAS for dizziness and headache were assessed. The pre and post-treatment VAS scores were compared (the improvement was evaluated together and individually, per drug used. Associations with clinical subgroups of patients were also assessed. Results: Of the 88 assessed records, 47 were eligible. We included patients that met the diagnostic criteria for VM and excluded those whose medical records were illegible and those of patients with other disorders causing dizziness and/or headache that did not meet the 2012 criteria for VM. 80.9% of the patients showed improvement with prophylaxis (p < 0.001. Amitriptyline, Flunarizine, Propranolol and Topiramate improved vestibular symptoms (p < 0.001 and headache (p < 0.015. The four drugs were effective in a statistically significant manner. There was a positive statistical association between the time of vestibular symptoms and clinical improvement. There was no additional benefit in hypertensive patients who used antihypertensive drugs as prophylaxis or depressed patients who used antidepressants in relation to other prophylactic drugs. Drug

  5. Cutaneous manifestations of HIV/AIDS: Part I | Dlova | Southern ...

    African Journals Online (AJOL)

    Human immunodeficiency virus (HIV) infection can lead to a variety of clinical cutaneous manifestations. These cutaneous disorders occur universally during the course of HIV infection. Cutaneous manifestations of HIV are very diverse. The course and clinical presentation of HIV in individuals who have access to highly ...

  6. Ultra-short-course booster is effective in recurrent grass pollen-induced allergic rhinoconjunctivitis.

    Science.gov (United States)

    Pfaar, O; Lang, S; Pieper-Fürst, U; Astvatsatourov, A; Gerich, F; Klimek, L; Kramer, M F; Reydelet, Y; Shah-Hosseini, K; Mösges, R

    2018-01-01

    A relevant proportion of allergic rhinoconjunctivitis (ARC) patients experience recurrent symptoms after successfully completing allergen immunotherapy (AIT). This prospective, controlled, noninterventional study used internationally standardized instruments to determine the clinical effects of a preseasonal, ultra-short-course booster AIT on clinical outcome parameters. This two-arm study included patients aged ≥12 years with recurrent grass pollen-induced seasonal AR who had completed a successful course of any grass pollen AIT at least 5 years before enrolment. Overall, 56 patients received one preseasonal short-course booster AIT using tyrosine-absorbed grass pollen allergoids containing the adjuvant monophosphoryl lipid A (MPL ® ); 51 control patients received symptomatic medication. The combined symptom and medication score (CSMS) was recorded in the (peak) grass pollen season. Furthermore, concomitant (antiallergic) medication use, the patients' state of health, Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) results and safety/tolerability of the treatment were assessed. The CSMS in the peak grass pollen season was significantly lower in the booster AIT group (Δ=38.4%, Pallergoids containing the adjuvant MPL ® effectively prevents re-occurrence of symptoms in patients with grass pollen-induced ARC. © 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.

  7. Advancing Sexuality Studies: A Short Course on Sexuality Theory and Research Methodologies

    Science.gov (United States)

    Fletcher, Gillian; Dowsett, Gary W.; Duncan, Duane; Slavin, Sean; Corboz, Julienne

    2013-01-01

    Critical Sexuality Studies is an emerging field of academic enquiry linked to an international network of advocacy agencies, activists, and political issues. This paper reports on the development of an advanced short course in sexuality theory and research, drawing on Critical Sexuality Studies and aiming directly at academics in developing…

  8. Exclusive breastfeeding, diarrhoeal morbidity and all-cause mortality in infants of HIV-infected and HIV uninfected mothers: an intervention cohort study in KwaZulu Natal, South Africa.

    Directory of Open Access Journals (Sweden)

    Nigel C Rollins

    Full Text Available INTRODUCTION: Antiretroviral drug interventions significantly reduce the risk of HIV transmission to infants through breastfeeding. We report diarrhoea prevalence and all-cause mortality at 12 months of age according to infant feeding practices, among infants born to HIV-infected and uninfected mothers in South Africa. METHODS: A non-randomised intervention cohort study that followed both HIV-infected and HIV-uninfected mothers and their infants until 18 months of age. Mothers were supported in their infant feeding choice. Detailed morbidity and vital status data were collected over the first year. At the time, only single dose nevirapine was available to prevent mother-to-child transmission of HIV. RESULTS: Among 2,589 infants, detailed feeding data and vital status were available for 1,082 HIV-exposed infants and 1,155 HIV non-exposed infants. Among exclusively breastfed (EBF infants there were 9.4 diarrhoeal days per 1,000 child days (95%CI. 9.12-9.82 while among infants who were never breastfed there were 15.6 diarrhoeal days per 1,000 child days (95%CI. 14.62-16.59. Exclusive breastfeeding was associated with fewer acute, persistent and total diarrhoeal events than mixed or no breastfeeding in both HIV-exposed infants and also infants of HIV uninfected mothers. In an adjusted cox regression analysis, the risk of death among all infants by 12 months of age was significantly greater in those who were never breastfed (aHR 3.5, p<0.001 or mixed fed (aHR 2.65, p<0.001 compared with those who were EBF. In separate multivariable analyses, infants who were EBF for shorter durations had an increased risk of death compared to those EBF for 5-6 months [aHR 2.18 (95% CI, 1.56-3.01; p<0.001]. DISCUSSION: In the context of antiretroviral drugs being scaled-up to eliminate new HIV infections among children, there is strong justification for financial and human resource investment to promote and support exclusive breastfeeding to improve HIV-free survival

  9. Long-term prophylactic insulin treatment can prevent spontaneous diabetes and thyroiditis development in the diabetes-prone bio-breeding rat, while short-term treatment is ineffective

    NARCIS (Netherlands)

    Visser, J.; Klatter, F; Vis, L; Groen, Harry; Strubbe, J.H.; Rozing, Nico

    Objective: Prophylactic insulin treatment has been demonstrated to reduce diabetes development in the diabetes-prone bio-breeding (DP-BB) rat. These prophylactic insulin treatments were given from 50 to 150 days of age. However, several data indicate that the diabetogenic process in DP-BB rats

  10. Synthesis and evaluation of "AZT-HEPT", "AZT-pyridinone", and "ddC-HEPT" conjugates as inhibitors of HIV reverse transcriptase.

    Science.gov (United States)

    Pontikis, R; Dollé, V; Guillaumel, J; Dechaux, E; Note, R; Nguyen, C H; Legraverend, M; Bisagni, E; Aubertin, A M; Grierson, D S; Monneret, C

    2000-05-18

    To test the concept that HIV reverse transcriptase could be effectively inhibited by "mixed site inhibitors", a series of seven conjugates containing both a nucleoside analogue component (AZT 1, ddC 2) and a nonnucleoside type inhibitor (HEPT analogue 12, pyridinone 27) were synthesized and evaluated for their ability to block HIV replication. The (N-3 and C-5)AZT-HEPT conjugates 15, 22, and 23 displayed 2-5 microM anti-HIV activity, but they had no effect on the replication of HIV-2 or the HIV-1 strain with the Y181C mutation. The (C-5)AZT-pyridinone conjugates 34-37 were found to be inactive. In marked contrast, the ddC-HEPT molecule 26 displayed the same potency (EC(50) = 0.45 microM) against HIV-1 (wild type and the Y181C nevirapine-resistant strain) and HIV-2 in cell culture. No synergistic effect was observed for these bis-substrate inhibitors, suggesting that the two individual inhibitor components in these molecules do not bind simultaneously in their respective sites. Interestingly, however, the results indicate that the AZT-HEPT conjugates and the ddC-HEPT derivative 26 inhibit reverse transcriptase (RT) in an opposite manner. One explanation for this difference is that the former compounds interact preferentially with the hydrophobic pocket in RT, whereas 26 (after supposed triphosphorylation) inhibits RT through binding in the catalytic site.

  11. A comparison of the long-term durability of nevirapine, efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study

    DEFF Research Database (Denmark)

    Reekie, J; Reiss, P; Ledergerber, B

    2011-01-01

    The durability of combination antiretroviral therapy (cART) regimens can be measured as time to discontinuation because of toxicity or treatment failure, development of clinical disease or serious long-term adverse events. The aim of this analysis was to compare the durability of nevirapine, efav...

  12. Economic evaluation of 3-drug antiretroviral regimens for the prevention of mother-to-child HIV transmission in Thailand.

    Science.gov (United States)

    Werayingyong, Pitsaphun; Phanuphak, Nittaya; Chokephaibulkit, Kulkunya; Tantivess, Sripen; Kullert, Nareeluk; Tosanguan, Kakanang; Butchon, Rukmanee; Voramongkol, Nipunporn; Boonsuk, Sarawut; Pilasant, Songyot; Kulpeng, Wantanee; Teerawattananon, Yot

    2015-03-01

    The current program for prevention of mother-to-child HIV transmission in Thailand recommends a 2-drugs regimen for HIV-infected pregnant women with a CD4 count >200 cells/mm(3). This study assesses the value for money of 3 antiretroviral drugs compared with zidovudine (AZT)+single-dose nevirapine (sd-NVP). A decision tree was constructed to predict costs and outcomes using the governmental perspective for assessing cost-effectiveness of 3-drug regimens: (1) AZT, lamivudine, and efavirenz and (2) AZT, 3TC, and lopinavir/ritonavir, in comparison with the current protocol, AZT+sd-NVP. The 3-drug antiretroviral regimens yield lower costs and better health outcomes compared with AZT+sd-NVP. Although these 3-drug regimens offer higher program costs and health care costs for premature birth, they save money significantly in regard to pediatric HIV treatment and treatment costs for drug resistance in mothers. The 3-drug regimens are cost-saving interventions. The findings from this study were used to support a policy change in the national recommendation. © 2013 APJPH.

  13. Prophylactic ibuprofed administration during pelvic irradiation

    International Nuclear Information System (INIS)

    Stryker, J.A.; Demers, L.M.; Mortel, R.

    1979-01-01

    Thirty-five patients who were to begin pelvic irradiation for malignant disease were randomized to receive ibuprofen 400 mg P.O. q.i.d. during their radiotherapy or standard therapy for radiation-induced gastrointestinal symptoms. Seventeen of 19 patients in the ibuprofen group completed the protocol. There was no significant difference in the daily stool frequency between the ibuprofen and control patients during the 5 to 6 week course of pelvic irradiation; the incidence and severity of diarrhea was the same. There was no significant difference in the incidence of nausea reported by the patients but the severity of nausea was less in the ibuprofen group; none of the 17 patients in the ibuprofen group reported vomiting at any time, whereas, 27% of the patients in the control group reported vomiting. The difference was statistically significant (p < 0.05). The data suggest that prophylactic ibuprofen administration may be beneficial in reducing the severity of nausea and preventing radiation-induced vomiting in patients who receive pelvic irradiation

  14. Brief Report: Decentralizing ART Supply for Stable HIV Patients to Community-Based Distribution Centers: Program Outcomes From an Urban Context in Kinshasa, DRC.

    Science.gov (United States)

    Vogt, Florian; Kalenga, Lucien; Lukela, Jean; Salumu, Freddy; Diallo, Ibrahim; Nico, Elena; Lampart, Emmanuel; Van den Bergh, Rafael; Shah, Safieh; Ogundahunsi, Olumide; Zachariah, Rony; Van Griensven, Johan

    2017-03-01

    Facility-based antiretroviral therapy (ART) provision for stable patients with HIV congests health services in resource-limited countries. We assessed outcomes and risk factors for attrition after decentralization to community-based ART refill centers among 2603 patients with HIV in Kinshasa, Democratic Republic of Congo, using a multilevel Poisson regression model. Death, loss to follow-up, and transfer out were 0.3%, 9.0%, and 0.7%, respectively, at 24 months. Overall attrition was 5.66/100 person-years. Patients with >3 years on ART, >500 cluster of differentiation type-4 count, body mass index >18.5, and receiving nevirapine but not stavudine showed reduced attrition. ART refill centers are a promising task-shifting model in low-prevalence urban settings with high levels of stigma and poor ART coverage.

  15. HIV-1-negative female sex workers sustain high cervical IFNɛ, low immune activation, and low expression of HIV-1-required host genes.

    Science.gov (United States)

    Abdulhaqq, S A; Zorrilla, C; Kang, G; Yin, X; Tamayo, V; Seaton, K E; Joseph, J; Garced, S; Tomaras, G D; Linn, K A; Foulkes, A S; Azzoni, L; VerMilyea, M; Coutifaris, C; Kossenkov, A V; Showe, L; Kraiselburd, E N; Li, Q; Montaner, L J

    2016-07-01

    Sex workers practicing in high HIV endemic areas have been extensively targeted to test anti-HIV prophylactic strategies. We hypothesize that in women with high levels of genital exposure to semen changes in cervico-vaginal mucosal and/or systemic immune activation will contribute to a decreased susceptibility to HIV-1 infection. To address this question, we assessed sexual activity and immune activation status (in peripheral blood), as well as cellular infiltrates and gene expression in ectocervical mucosa biopsies in female sex workers (FSWs; n=50), as compared with control women (CG; n=32). FSWs had low-to-absent HIV-1-specific immune responses with significantly lower CD38 expression on circulating CD4(+) or CD8(+) T-cells (both: PHIV-1 integration and replication. A correlative relationship between semen exposure and elevated type-1 IFN expression in FSWs was also established. Overall, our data suggest that long-term condomless sex work can result in multiple changes within the cervico-vaginal compartment that would contribute to sustaining a lower susceptibility for HIV-1 infection in the absence of HIV-specific responses.

  16. A model of directional selection applied to the evolution of drug resistance in HIV-1.

    Science.gov (United States)

    Seoighe, Cathal; Ketwaroo, Farahnaz; Pillay, Visva; Scheffler, Konrad; Wood, Natasha; Duffet, Rodger; Zvelebil, Marketa; Martinson, Neil; McIntyre, James; Morris, Lynn; Hide, Winston

    2007-04-01

    Understanding how pathogens acquire resistance to drugs is important for the design of treatment strategies, particularly for rapidly evolving viruses such as HIV-1. Drug treatment can exert strong selective pressures and sites within targeted genes that confer resistance frequently evolve far more rapidly than the neutral rate. Rapid evolution at sites that confer resistance to drugs can be used to help elucidate the mechanisms of evolution of drug resistance and to discover or corroborate novel resistance mutations. We have implemented standard maximum likelihood methods that are used to detect diversifying selection and adapted them for use with serially sampled reverse transcriptase (RT) coding sequences isolated from a group of 300 HIV-1 subtype C-infected women before and after single-dose nevirapine (sdNVP) to prevent mother-to-child transmission. We have also extended the standard models of codon evolution for application to the detection of directional selection. Through simulation, we show that the directional selection model can provide a substantial improvement in sensitivity over models of diversifying selection. Five of the sites within the RT gene that are known to harbor mutations that confer resistance to nevirapine (NVP) strongly supported the directional selection model. There was no evidence that other mutations that are known to confer NVP resistance were selected in this cohort. The directional selection model, applied to serially sampled sequences, also had more power than the diversifying selection model to detect selection resulting from factors other than drug resistance. Because inference of selection from serial samples is unlikely to be adversely affected by recombination, the methods we describe may have general applicability to the analysis of positive selection affecting recombining coding sequences when serially sampled data are available.

  17. Mother-to-child transmission of HIV-1 in sub-Saharan Africa: past, present and future challenges.

    Science.gov (United States)

    Taha, Taha E

    2011-05-23

    HIV prevalence continues to be high among women of reproductive age in sub-Saharan Africa. In 2007 the HIV prevalence among pregnant women attending antenatal clinics was >20% in the southern African counties of Botswana, Swaziland, South Africa and Lesotho. Mother-to-child transmission (MTCT) of HIV can occur in-utero, intrapartum or postnatally. Without any preventive measure the overall rate of the MTCT of HIV in breastfeeding women could be 25-45%. Prior to the discovery of successful antiretroviral interventions to prevent the MTCT of HIV in sub-Saharan Africa (before 1999), innovative research determined the magnitude of the problem, the impact of the HIV epidemic on mothers and children, and the main risk factors associated with MTCT. Non-antiretroviral interventions conducted before 1999 such as washing the birth canal with antiseptics and antenatal supplementation with vitamin A did not reduce the MTCT of HIV. However, during the period 1999 to present, major successes were made in the prevention of the MTCT of HIV. The use of single-dose nevirapine prophylaxis to the mother and infant reduced the MTCT of HIV to ~12%. Subsequently, longer prophylaxis and combined antiretroviral regimens were shown to be highly effective and very low HIV transmission rates comparable to those in developed countries were reported in some clinical trial settings in sub-Saharan Africa. The future is promising but challenges remain. The current successful intervention modalities are entirely dependent on antiretrovirals and breastfeeding continues to be vital for the survival of the child in the African setting. Reviewing past and present achievements assists in focusing future research and development of prevention programs. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

    Science.gov (United States)

    Pakker, N G; Kroon, E D; Roos, M T; Otto, S A; Hall, D; Wit, F W; Hamann, D; van der Ende, M E; Claessen, F A; Kauffmann, R H; Koopmans, P P; Kroon, F P; ten Napel, C H; Sprenger, H G; Weigel, H M; Montaner, J S; Lange, J M; Reiss, P; Schellekens, P T; Miedema, F

    1999-02-04

    Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported

  19. Fused heterocyclic compounds bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 1: design, synthesis and biological evaluation of novel 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives.

    Science.gov (United States)

    Tian, Ye; Du, Deping; Rai, Diwakar; Wang, Liu; Liu, Huiqing; Zhan, Peng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

    2014-04-01

    In our continuous efforts to identify novel potent HIV-1 NNRTIs, a novel class of 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities in MT4 cell cultures. Biological results showed that most of the tested compounds displayed excellent activity against wild-type HIV-1 with a wide range of EC50 values from 5.98 to 0.07μM. Among the active compounds, 5a was found to be the most promising analogue with an EC50 of 0.07μM against wild-type HIV-1 and very high selectivity index (SI, 3999). Compound 5a was more effective than the reference drugs nevirapine (by 2-fold) and delavirdine (by 2-fold). In order to further confirm their binding target, an HIV-1 RT inhibitory assay was also performed. Furthermore, SAR analysis among the newly synthesized compounds was discussed and the binding mode of the active compound 5a was rationalized by molecular modeling studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. High pregnancy intentions and missed opportunities for patient-provider communication about fertility in a South African cohort of HIV-positive women on antiretroviral therapy.

    Science.gov (United States)

    Schwartz, Sheree R; Mehta, Shruti H; Taha, Taha E; Rees, Helen V; Venter, Francois; Black, Vivian

    2012-01-01

    High fertility intentions amongst HIV-positive women have been reported elsewhere. Less is known about how clinical and HIV treatment characteristics correlate with fertility intentions. We use cross-sectional baseline data from a prospective cohort study to assess pregnancy intentions and patient-provider communication around fertility. Non-pregnant, HIV-positive women aged 18-35 on ART were recruited through convenience sampling at Johannesburg antiretroviral (ART) treatment facilities. Among the 850 women in this analysis, those on efavirenz had similar fertility intentions over the next year as women on nevirapine-based regimens (33% vs. 38%). In multivariate analysis, recent ART initiation was associated with higher current fertility intentions; there was no association with CD4 cell count. Forty-one percent of women had communicated with providers about future pregnancy options. Women on ART may choose to conceive at times that are sub-optimal for maternal, child and partner health outcomes and should be routinely counseled around safer pregnancy options.

  1. Open study of short course Fleroxacin for Typhoid and Paratyphoid Fever

    Directory of Open Access Journals (Sweden)

    R. H.H. Nelwan

    2002-03-01

    Full Text Available The objective of this study was to evaluate clinical and bacteriological effect of short course fleroxacin in uncomplicated typhoid and paratyphoid fever patients. Four hundred mg of fleroxacin was given oraly once daily for a period of 3 to 5 days. The diagnosis of typhoid and paratyphoid fever was established by clinical picture as well as blood culture or Widal serology test. Thirty patients in whom the clinical picture was confirmed as a typhoid or paratyphoid infection were eligible for this investigation. They consisted of 15 males and 15 females ranging in age from 18-38 years average 27.5 years of whom 18 were diagnosed by blood culture consisting of 16 S.typhi positive cases and two S.paratyphi A, while 12 other cases were positively confirmed by serial Widal agglutination serology. These cases suffered from fever between 3-14 days with a minimum recorded body temperature elevation of 38.5 degrees Celsius. Clinical response with defervescence of fever was obtained in the positive blood culture group within 3 days (8 patients including 2 cases positive for S.paratyphi A and within two additional days (5 days in the remaining 10 cases. In the twelve cases with a positive serology for typhoid fever a clinical response was obtained for defervescence within 3 days (6 cases with 4 of these cases were on 3 days of fleroxacin and 2 cases on 5 days of fleroxacin. In the remaining 6 serologic positive cases fever resolved after 4-6 days with an average of 5 days with one on 3 days of fleroxacin and the rest (5 cases on 5 days of fleroxacin. All positive blood culture cases reverted to negative after the fleroxacin course. No relapse or carrier state was recorded in this serie. It may be concluded that a 3 to 5 days closely monitored course of fleroxacin has excellent clinical as well as bacteriological efficacy in noncomplicated typhoid and paratyphoid fever. (Med J Indones 2002; 11: 41-7Keywords: fluoroquinolones, enteric infections, short

  2. Barriers to access prevention of mother-to-child transmission for HIV positive women in a well-resourced setting in Vietnam

    Directory of Open Access Journals (Sweden)

    Wright Pamela

    2008-04-01

    Full Text Available Abstract Background According to Vietnamese policy, HIV-infected women should have access at least to HIV testing and Nevirapine prophylaxis, or where available, to adequate counselling, HIV infection staging, ARV prophylaxis, and infant formula. Many studies in high HIV prevalence settings have reported low coverage of PMTCT services, but there have been few reports from low HIV prevalence settings, such as Asian countries. We investigated the access of HIV-infected pregnant women to PMTCT services in the well-resourced setting of the capital city, Hanoi. Methods Fifty-two HIV positive women enrolled in a self-help group in Hanoi were consulted, through in-depth interviews and bi-weekly meetings, about their experiences in accessing PMTCT services. Results Only 44% and 20% of the women had received minimal and comprehensive PMTCT services, respectively. Nine women did not receive any services. Twenty-two women received no counselling. The women reported being limited by lack of knowledge and information due to poor counselling, gaps in PMTCT services, and fear of stigma and discrimination. HIV testing was done too late for optimal interventions and poor quality of care by health staff was frequently mentioned. Conclusion In a setting where PMTCT is available, HIV-infected women and children did not receive adequate care because of barriers to accessing those services. The results suggest key improvements would be improving quality of counselling and making PMTCT guidelines available to health services. Women should receive early HIV testing with adequate counselling, safe care and prophylaxis in a positive atmosphere towards HIV-infected women.

  3. Strengthening capacity for monitoring and evaluation through short course training in Kenya

    Directory of Open Access Journals (Sweden)

    Hesborn Wao

    2017-04-01

    Conclusions: This study provides preliminary evidence of potential of the use of short course training as an approach to strengthening capacity in M&E in less-developed countries such as Kenya. It underscores the importance of participants’ self-stated objective(s as an element to be considered in the enhancement of knowledge, attitudes and skills needed for acceptable capacity building in M&E.

  4. High Rates of All-cause and Gastroenteritis-related Hospitalization Morbidity and Mortality among HIV-exposed Indian Infants

    Directory of Open Access Journals (Sweden)

    Tripathy Srikanth

    2011-07-01

    Full Text Available Abstract Background HIV-infected and HIV-exposed, uninfected infants experience a high burden of infectious morbidity and mortality. Hospitalization is an important metric for morbidity and is associated with high mortality, yet, little is known about rates and causes of hospitalization among these infants in the first 12 months of life. Methods Using data from a prevention of mother-to-child transmission (PMTCT trial (India SWEN, where HIV-exposed breastfed infants were given extended nevirapine, we measured 12-month infant all-cause and cause-specific hospitalization rates and hospitalization risk factors. Results Among 737 HIV-exposed Indian infants, 93 (13% were HIV-infected, 15 (16% were on HAART, and 260 (35% were hospitalized 381 times by 12 months of life. Fifty-six percent of the hospitalizations were attributed to infections; gastroenteritis was most common accounting for 31% of infectious hospitalizations. Gastrointestinal-related hospitalizations steadily increased over time, peaking around 9 months. The 12-month all-cause hospitalization, gastroenteritis-related hospitalization, and in-hospital mortality rates were 906/1000 PY, 229/1000 PY, and 35/1000 PY respectively among HIV-infected infants and 497/1000 PY, 107/1000 PY, and 3/1000 PY respectively among HIV-exposed, uninfected infants. Advanced maternal age, infant HIV infection, gestational age, and male sex were associated with higher all-cause hospitalization risk while shorter duration of breastfeeding and abrupt weaning were associated with gastroenteritis-related hospitalization. Conclusions HIV-exposed Indian infants experience high rates of all-cause and infectious hospitalization (particularly gastroenteritis and in-hospital mortality. HIV-infected infants are nearly 2-fold more likely to experience hospitalization and 10-fold more likely to die compared to HIV-exposed, uninfected infants. The combination of scaling up HIV PMTCT programs and implementing proven health

  5. Collision Avoidance Short Course: Conjunction Assessment Risk Analysis - NASA Robotic CARA. Part I: ; Theory

    Science.gov (United States)

    Hejduk, M. D.; Frigm, Ryan C.

    2015-01-01

    Satellite conjunction assessment is perhaps the fastest growing area in space situational awareness and protection with military, civil and commercial satellite owner-operators embracing more and more sophisticated processes to avoid the avoidable - namely collisions between high value space assets and orbital debris. NASA and Centre National d'Etudes Spatiales (CNES) have collaborated to offer an introductory short course on all the major aspects of the conjunctions assessment problem. This half-day course will cover satellite conjunction dynamics and theory. Joint Space Operations Center (JsPOC) conjunction data products, major risk assessment parameters and plots, conjunction remediation decision support, and present and future challenges. This briefing represents the NASA portion of the course.

  6. Benefit of brain prophylactic irradiation in patients suffering from a small-cell bronchial cancer: retrospective study on 289 cases

    International Nuclear Information System (INIS)

    Assouline, A.; Tai, P.; Jancewicz, M.; Joseph, K.; Krzisch, C.; Yu, E.

    2011-01-01

    The authors report a study which aimed at determining the benefit of a brain prophylactic irradiation for patients suffering from a localized small-cell bronchial cancer and in partial response to the local-regional treatment of their disease. A retrospective analysis has been performed on a set of 289 patients who had been treated by chemo-radiotherapy with or without brain prophylactic irradiation between 1981 and 2007. Data are discussed in terms of remission level, survival with respect to the level of response to the local-regional treatment. Depending on this response level the irradiation increases or not the probability of global survival, or the probability of specific survival. Short communication

  7. Progress towards Elimination of HIV Mother-to-Child Transmission in the Dominican Republic from 1999 to 2011

    Directory of Open Access Journals (Sweden)

    Osvaldo Lorenzo

    2012-01-01

    Full Text Available In 1999, prevention of mother-to-child transmission (pMTCT using antiretrovirals was introduced in the Dominican Republic (DR. Highly active antiretroviral therapy (HAART was introduced for immunosuppressed persons in 2004 and for pMTCT in 2008. To assess progress towards MTCT elimination, data from requisitions for HIV nucleic acid amplification tests for diagnosis of HIV infection in perinatally exposed infants born in the DR from 1999 to 2011 were analyzed. The MTCT rate was 142/1,274 (11.1% in 1999–2008 and 12/302 (4.0% in 2009–2011 (P<.001, with a rate of 154/1,576 (9.8% for both periods combined. This decline was associated with significant increases in the proportions of women who received prenatal HAART (from 12.3% to 67.9% and infants who received exclusive formula feeding (from 76.3% to 86.1% and declines in proportions of women who received no prenatal antiretrovirals (from 31.9% to 12.2% or received only single-dose nevirapine (from 39.5% to 19.5%. In 2007, over 95% of DR pregnant women received prenatal care, HIV testing, and professionally attended delivery. However, only 58% of women in underserved sugarcane plantation communities (2007 and 76% in HIV sentinel surveillance hospitals (2003–2005 received their HIV test results. HIV-MTCT elimination is feasible but persistent lack of access to critical pMTCT measures must be addressed.

  8. Current perspectives in HIV post-exposure prophylaxis

    Directory of Open Access Journals (Sweden)

    Sultan B

    2014-10-01

    Full Text Available Binta Sultan,1,2 Paul Benn,1 Laura Waters1 1Department of Genitourinary Medicine, Mortimer Market Centre, Central and North West London NHS Foundation Trust, London, UK; 2Centre for Sexual Health and HIV Research, University College London, London, UK Abstract: The incidence of human immunodeficiency virus (HIV infection continues to rise among core groups and efforts to reduce the numbers of new infections are being redoubled. Post-exposure prophylaxis (PEP is the use of short-term antiretroviral therapy (ART to reduce the risk of acquisition of HIV infection following exposure. Current guidelines recommend a 28-day course of ART within 36–72 hours of exposure to HIV. As long as individuals continue to be exposed to HIV there will be a role for PEP in the foreseeable future. Nonoccupational PEP, the vast majority of which is for sexual exposure (PEPSE, has a significant role to play in HIV prevention efforts. Awareness of PEP and its availability for both clinicians and those who are eligible to receive it are crucial to ensure that PEP is used to its full potential in any HIV prevention strategy. In this review, we provide current evidence for the use of PEPSE, assessment of the risk of HIV transmission, indications for PEP, drug regimens, and management of patients started on PEP. We summarize national and international guidelines for the use of PEPSE. We explore the place of PEP within the wider strategy of reducing HIV incidence rates in the era of treatment as prevention and pre-exposure prophylaxis. We also consider the implications of recent data from interventional and observational studies demonstrating significant reductions in the risk of HIV transmission within a serodiscordant relationship if the HIV-positive partner is taking effective ART upon PEP guidelines. Keywords: post-exposure prophylaxis, pre-exposure prophylaxis, treatment as prevention, human immunodeficiency virus

  9. A Multicultural, Multidisciplinary Short Course to Introduce Recently Graduated Engineers to the Global Nature of Professional Practice

    Science.gov (United States)

    Hazelton, Pam; Malone, Molly; Gardner, Anne

    2009-01-01

    Since 2001, the International Institute of Women in Engineering (IIWE) at EPF, Ecole d'ingenieurs generaliste, Sceaux, France, has conducted a 3 week short course for culturally and discipline diverse, recently graduated and final year engineering students. The aim of this course is to introduce young engineers to broad global concepts and issues…

  10. original article socio-demographic characteristics of patients

    African Journals Online (AJOL)

    boaz

    Human Immunodeficiency Virus (HIV) is RNA virus that causes Acquired Immune Deficiency ... blood of an HIV infected person. ... immune system has taken place as seen by the presence .... education are mostly affected with the disease due to .... retroviral drug) Nevirapine. ... interventions together in a broad attack on the.

  11. Performance of Clinical Criteria for Screening of Possible Antiretroviral Related Mitochondrial Toxicity in HIV-Infected Children in Accra.

    Science.gov (United States)

    Langs-Barlow, Allison; Renner, Lorna; Katz, Karol; Northrup, Veronika; Paintsil, Elijah

    2013-01-01

    Mitochondrial damage is implicated in highly active antiretroviral therapy (HAART) toxicity. HIV infection also causes mitochondrial toxicity (MT). Differentiating between the two is critical for HIV management. Our objective was to test the utility of the Mitochondrial Disease Criteria (MDC) and the Enquête Périnatale Française (EPF) to screen for possible HAART related MT in HIV-infected children in Ghana. The EPF and MDC are compilations of clinical symptoms, or criteria, of MT: a (+) score indicates possible MT. We applied these criteria retrospectively to 403 charts of HIV-infected children. Of those studied, 331/403 received HAART. Comparing HAART exposed and HAART naïve children, the difference in EPF score, but not MDC, approached significance (P = 0.1). Young age at HIV diagnosis or at HAART initiation was associated with (+) EPF (P ≤ 0.01). Adherence to HAART trended toward an association with (+) EPF (P = 0.09). Exposure to nevirapine, abacavir, or didanosine increased risk of (+) EPF (OR = 3.55 (CI = 1.99-6.33), 4.76 (2.39-9.43), 4.93 (1.29-18.87)). Neither EPF nor MDC identified a significant difference between HAART exposed or naïve children regarding possible MT. However, as indicators of HAART exposure are associated with (+) EPF, it may be a candidate for prospective study of possible HAART related MT in resource-poor settings.

  12. Performance of Clinical Criteria for Screening of Possible Antiretroviral Related Mitochondrial Toxicity in HIV-Infected Children in Accra

    Directory of Open Access Journals (Sweden)

    Allison Langs-Barlow

    2013-01-01

    Full Text Available Mitochondrial damage is implicated in highly active antiretroviral therapy (HAART toxicity. HIV infection also causes mitochondrial toxicity (MT. Differentiating between the two is critical for HIV management. Our objective was to test the utility of the Mitochondrial Disease Criteria (MDC and the Enquête Périnatale Française (EPF to screen for possible HAART related MT in HIV-infected children in Ghana. The EPF and MDC are compilations of clinical symptoms, or criteria, of MT: a (+ score indicates possible MT. We applied these criteria retrospectively to 403 charts of HIV-infected children. Of those studied, 331/403 received HAART. Comparing HAART exposed and HAART naïve children, the difference in EPF score, but not MDC, approached significance (. Young age at HIV diagnosis or at HAART initiation was associated with (+ EPF (. Adherence to HAART trended toward an association with (+ EPF (. Exposure to nevirapine, abacavir, or didanosine increased risk of (+ EPF (OR = 3.55 (CI = 1.99–6.33, 4.76 (2.39–9.43, 4.93 (1.29–18.87. Neither EPF nor MDC identified a significant difference between HAART exposed or naïve children regarding possible MT. However, as indicators of HAART exposure are associated with (+ EPF, it may be a candidate for prospective study of possible HAART related MT in resource-poor settings.

  13. University of New Mexico short course in nuclear criticality safety: Training for new NCS [nuclear criticality safety] specialists

    International Nuclear Information System (INIS)

    Busch, R.D.

    1990-01-01

    Since 1973, the University of New Mexico (UNM) has given ten short courses in nuclear criticality safety (NCS). Generally, thee have been given every other year, although in 1989 it was decided to offer the course on an annual basis. This decision was primarily based on the large demand for NCS specialists and a large turnover rate in the industry. The purpose of the course is to provide a 1-week overview of NCS. The typical student has been involved in NCS for <1 yr, although it many cases they have been associated with the nuclear industry in other capacities for many years. The short course is conducted at several levels. Carefully prepared lectures provide the information framework for selected topics. The following topics are covered in the course: basic reactor theory, criticality accidents and consequences, hand calculations, administration of a criticality safety program, regulators and their processes, computer methods and applications, experimental methods and correlations, overview of some process operations, and transportation and storage issues in NCS

  14. Forest and grassland carbon in North America: A short course for land managers

    Science.gov (United States)

    Chris Swanston; Michael J. Furniss; Kristen Schmitt; Jeffrey Guntle; Maria Janowiak; Sarah Hines

    2012-01-01

    This multimedia short-course presents a range of information on the science, management and policy of forest and grassland carbon. Forests and grasslands worldwide play a critical role in storing carbon and sequestering greenhouse gases from the atmosphere. The U.S. Forest Service, which manages 193 million acres of forests and grasslands, emphasizes the need for...

  15. Conditional live virus as a novel approach towards a safe live attenuated HIV vaccine

    NARCIS (Netherlands)

    Das, Atze T.; Zhou, Xue; Vink, Monique; Klaver, Bep; Berkhout, Ben

    2002-01-01

    To control the worldwide spread of HIV, a safe and effective prophylactic vaccine is urgently needed. Studies with the simian immunodeficiency virus demonstrated that a live attenuated virus can be effective as a vaccine, but serious concerns about the safety of such a vaccine virus have arisen. We

  16. Prophylactic antibiotic treatment in severe acute ischemic stroke: the Antimicrobial chemopRrophylaxis for Ischemic STrokE In MaceDonIa-Thrace Study (ARISTEIDIS).

    Science.gov (United States)

    Tziomalos, Konstantinos; Ntaios, George; Miyakis, Spiros; Papanas, Nikolaos; Xanthis, Andreas; Agapakis, Dimitrios; Milionis, Haralampos; Savopoulos, Christos; Maltezos, Efstratios; Hatzitolios, Apostolos I

    2016-10-01

    Infections represent a leading cause of mortality in patients with acute ischemic stroke, but it is unclear whether prophylactic antibiotic treatment improves the outcome. We aimed to evaluate the effects of this treatment on infection incidence and short-term mortality. This was a pragmatic, prospective multicenter real-world analysis of previously independent consecutive patients with acute ischemic stroke who were >18 years, and who had at admission National Institutes of Health Stroke Scale (NIHSS) >11. Patients with infection at admission or during the preceding month, with axillary temperature at admission >37 °C, with chronic inflammatory diseases or under treatment with corticosteroids were excluded from the study. Among 110 patients (44.5 % males, 80.2 ± 6.8 years), 31 (28.2 %) received prophylactic antibiotic treatment, mostly cefuroxime (n = 21). Prophylactic antibiotic treatment was administered to 51.4 % of patients who developed infection, and to 16.4 % of patients who did not (p antibiotic treatment (RR 5.84, 95 % CI 2.03-16.79, p antibiotic treatment did not differ between patients who died during hospitalization and those discharged, or between patients who died during hospitalization or during follow-up and those who were alive 3 months after discharge. Prophylactic administration of antibiotics in patients with severe acute ischemic stroke is associated with an increased risk of infection during hospitalization, and does not affect short-term mortality risk.

  17. CCL28 induces mucosal homing of HIV-1-specific IgA-secreting plasma cells in mice immunized with HIV-1 virus-like particles.

    Directory of Open Access Journals (Sweden)

    Veronica Rainone

    Full Text Available Mucosae-associated epithelial chemokine (MEC or CCL28 binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASCs in the mucosal lamina propria. The ability of this chemokine to enhance migration of IgA-ASCs to mucosal sites was assessed in a mouse immunization model using HIV-1(IIIB Virus-like particles (VLPs. Mice receiving either HIV-1(IIIB VLPs alone, CCL28 alone, or the irrelevant CCL19 chemokine were used as controls. Results showed a significantly increased CCR3 and CCR10 expression on CD19(+ splenocytes of HIV-1(IIIB VPL-CCL28-treated mice. HIV-1 Env-specific IFN-γ, IL-4 and IL-5 production, total IgA, anti-Env IgA as well as gastro-intestinal mucosal IgA-secreting plasma cells were also significantly augmented in these mice. Notably, sera and vaginal secretions from HIV-1(IIIB VLP-CCL28-treated mice exhibited an enhanced neutralizing activity against both a HIV-1/B-subtype laboratory strain and a heterologous HIV-1/C-subtype primary isolate. These data suggest that CCL28 could be useful in enhancing the IgA immune response that will likely play a pivotal role in prophylactic HIV vaccines.

  18. A Conserved Target Site in HIV-1 Gag RNA is Accessible to Inhibition by Both an HDV Ribozyme and a Short Hairpin RNA

    Directory of Open Access Journals (Sweden)

    Robert J Scarborough

    2014-01-01

    Full Text Available Antisense-based molecules targeting HIV-1 RNA have the potential to be used as part of gene or drug therapy to treat HIV-1 infection. In this study, HIV-1 RNA was screened to identify more conserved and accessible target sites for ribozymes based on the hepatitis delta virus motif. Using a quantitative screen for effects on HIV-1 production, we identified a ribozyme targeting a highly conserved site in the Gag coding sequence with improved inhibitory potential compared to our previously described candidates targeting the overlapping Tat/Rev coding sequence. We also demonstrate that this target site is highly accessible to short hairpin directed RNA interference, suggesting that it may be available for the binding of antisense RNAs with different modes of action. We provide evidence that this target site is structurally conserved in diverse viral strains and that it is sufficiently different from the human transcriptome to limit off-target effects from antisense therapies. We also show that the modified hepatitis delta virus ribozyme is more sensitive to a mismatch in its target site compared to the short hairpin RNA. Overall, our results validate the potential of a new target site in HIV-1 RNA to be used for the development of antisense therapies.

  19. Assessing missed opportunities for the prevention of mother-to-child HIV transmission in an Eastern Cape local service area.

    Science.gov (United States)

    Rispel, L C; Peltzer, K; Phaswana-Mafuya, N; Metcalf, C A; Treger, L

    2009-03-01

    Prevention of new HIV infections is a critical imperative for South Africa; the prevention of mother-to-child transmission (PMTCT) is one of the most efficacious HIV prevention interventions. Assessment of a PMTCT programme to determine missed opportunities. The Kouga local service area (LSA), bordering Nelson Mandela Bay Municipality (Port Elizabeth) in the Eastern Cape. An assessment was conducted in 2007 before implementing technical support for strengthening the PMTCT programme, including: interviews with 20 PMTCT managers, 4 maternity staff and 27 other health workers on service provision, management, infrastructure, human resources and the health information system; 296 antenatal clinic users on their service perceptions; 70 HIV-positive women on HIV knowledge, infant feeding, coping, support and service perceptions; 8 representatives from community organisations and 101 traditional health practitioners (THPs). Observations were conducted during site visits to health facilities, and the District Health Information System (DHIS) data were reviewed. Staff had high levels of awareness of HIV policies and most had received some relevant training. Nevirapine uptake varied by clinic, with an average of 56%. There were many missed opportunities for PMTCT, with 67% of pregnant women tested for HIV and only 43% of antenatal care attendees tested during a previous pregnancy. Only 6% of HIV-positive women reported support group participation. Reducing missed opportunities for PMTCT requires strengthening of the formal health sector, intersectoral liaison, and greater community support. Priority areas that require strengthening in the formal health sector include HIV counselling and testing; family planning and nutrition counselling; infant follow-up; human resources; and monitoring and evaluation.

  20. Building partnerships to address the HIV epidemic.

    Science.gov (United States)

    Chua, A C; Leo, Y S; Lee, C C

    2008-05-01

    Batam is one of the islands comprising the Riau Province in Indonesia, and is closest to Singapore. It is a popular destination of many Singaporeans. Surveillance reports among commercial sex workers conducted in Batam showed the prevalence rate of human immunodeficiency virus (HIV) is 16.2 percent. At the end of 2006, the total number of HIV-infected Singaporeans was 3,060, the majority being infected via heterosexual transmission. The aim of the Indonesian government is to rapidly scale up HIV treatment to those needing it. One of the factors critical to the rapid scale-up is healthcare worker training. An intersectoral collaboration addressing the issue of HIV care and treatment with a hospital in Batam was created. The first activity of the collaboration was a two-day HIV training course conducted in February 2007. The aim of the course was to provide a basic understanding of HIV, as well as knowledge on common opportunistic infections that may present to a general hospital or clinical setting. 34 doctors from 23 institutions in Batam and three doctors from two hospitals in the Riau Islands attended the two-day HIV training course. The participants found the training very useful and highly relevant. This first HIV training provided a foundation to build on further HIV education. It is our belief that through the HIV training programme, there will be more awareness of HIV among the various medical institutions in Batam. As the HIV epidemic knows no borders, working with neighbouring countries is one strategy that deserves attention.

  1. Body image and psychological distress after prophylactic mastectomy and breast reconstruction in genetically predisposed women: A prospective long-term follow-up study

    NARCIS (Netherlands)

    den Heijer, M.; Seynaeve, C.; Timman, R.; Duivenvoorden, H.J.; Vanheusden, K.; Tilanus-Linthorst, M.; Menke-Pluijmers, M.B.E.; Tibben, A.

    2012-01-01

    Purpose: To explore the course of psychological distress and body image at long-term follow-up (6-9 years) after prophylactic mastectomy and breast reconstruction (PM/BR) in women at risk for hereditary breast cancer, and to identify pre-PM risk factors for poor body image on the long-term. Methods:

  2. Body image and psychological distress after prophylactic mastectomy and breast reconstruction in genetically predisposed women: a prospective long-term follow-up study.

    NARCIS (Netherlands)

    Heijer, M. den; Seynaeve, C.; Timman, R.; Duivenvoorden, H.J.; Vanheusden, K.; Tilanus-Linthorst, M.; Menke-Pluijmers, M.B.; Tibben, A.

    2012-01-01

    PURPOSE: To explore the course of psychological distress and body image at long-term follow-up (6-9 years) after prophylactic mastectomy and breast reconstruction (PM/BR) in women at risk for hereditary breast cancer, and to identify pre-PM risk factors for poor body image on the long-term. METHODS:

  3. Prevention of mother-to-child transmission of HIV: cost-effectiveness of antiretroviral regimens and feeding options in Rwanda.

    Directory of Open Access Journals (Sweden)

    Agnes Binagwaho

    Full Text Available Rwanda's National PMTCT program aims to achieve elimination of new HIV infections in children by 2015. In November 2010, Rwanda adopted the WHO 2010 ARV guidelines for PMTCT recommending Option B (HAART for all HIV-positive pregnant women extended throughout breastfeeding and discontinued (short course-HAART only for those not eligible for life treatment. The current study aims to assess the cost-effectiveness of this policy choice.Based on a cohort of HIV-infected pregnant women in Rwanda, we modelled the cost-effectiveness of six regimens: dual ARV prophylaxis with either 12 months breastfeeding or replacement feeding; short course HAART (Sc-HAART prophylaxis with either 6 months breastfeeding, 12 months breastfeeding, or 18 months breastfeeding; and Sc-HAART prophylaxis with replacement feeding. Direct costs were modelled based on all inputs in each scenario and related unit costs. Effectiveness was evaluated by measuring HIV-free survival at 18 months. Savings correspond to the lifetime costs of HIV treatment and care avoided as a result of all vertical HIV infections averted.All PMTCT scenarios considered are cost saving compared to "no intervention." Sc-HAART with 12 months breastfeeding or 6 months breastfeeding dominate all other scenarios. Sc-HAART with 12 months breastfeeding allows for more children to be alive and HIV-uninfected by 18 months than Sc-HAART with 6 months breastfeeding for an incremental cost per child alive and uninfected of 11,882 USD. This conclusion is sensitive to changes in the relative risk of mortality by 18 months for exposed HIV-uninfected children on replacement feeding from birth and those who were breastfed for only 6 months compared to those breastfeeding for 12 months or more.Our findings support the earlier decision by Rwanda to adopt WHO Option B and could inform alternatives for breastfeeding duration. Local contexts and existing care delivery models should be part of national policy decisions.

  4. The Angelina Jolie Effect in Jewish Law: Prophylactic Mastectomy and Oophorectomy in BRCA Carriers

    Directory of Open Access Journals (Sweden)

    Sharon Galper Grossman

    2015-10-01

    Full Text Available Background: Following the announcement of actress Angelina Jolie’s prophylactic bilateral mastectomies and subsequent prophylactic oophorectomy, there has been a dramatic increase in interest in BRCA testing and prophylactic surgery. Objective: To review current medical literature on the benefits of prophylactic mastectomy and oophorectomy among BRCA-positive women and its permissibility under Jewish law. Results: Recent literature suggests that in BRCA-positive women who undergo prophylactic oophorectomy the risk of dying of breast cancer is reduced by 90%, the risk of dying of ovarian cancer is reduced by 95%, and the risk of dying of any cause is reduced by 77%. The risk of breast cancer is further reduced by prophylactic mastectomy. Prophylactic oophorectomy and prophylactic mastectomy pose several challenges within Jewish law that call into question the permissibility of surgery, including mutilation of a healthy organ, termination of fertility, self-wounding, and castration. A growing number of Jewish legal scholars have found grounds to permit prophylactic surgery among BRCA carriers, with some even obligating prophylactic mastectomy and oophorectomy. Conclusion: Current data suggest a significant reduction in mortality from prophylactic mastectomy and oophorectomy in BRCA carriers. While mutilation of healthy organs is intrinsically forbidden in Jewish law, the ability to preserve human life may contravene and even mandate prophylactic surgery.

  5. The role of prophylactic cranial irradiation in small cell lung cancer

    International Nuclear Information System (INIS)

    Kiricuta, I.C.; Bohndorf, W.

    1996-01-01

    To analyse if prophylactic cranial irradiation is small cell lung cancer for improved survival is indicated; if adjuvant irradiation could cure the microscopic disease; if and how late effects could be minimized. Data from randomized trials and retrospective studies are critically analysed related to the incidence of central nervous system (CNS) metastases in limited disease patients in complete remission with or without prophylactic cranial irradiation. The mechanisms of late effects on CNS of prophylactic cranial irradiation and combined treatment are presented. Prophylactic cranial irradiation could decrease the incidence of CNS metastases but could not improve survival. A subgroup of patients (9 to 14%) most likely to benefit from prophylactic cranial irradiation includes patients who are likely to have an isolated CNS failure. The actual used total dose in the range 30 to 40 Gy could only conditionally decrease the CNS failure. Higher total and/or daily doses and combined treatment are related with potentially devastating neurologic and intellectual disabilities. No prospective randomized trial has demonstrated a significant survival advantage for patients treated with prophylactic cranial irradiation. Prophylactic cranial irradiation is capable of reducing the incidence of cerebral metastases and delays CNS failure. A subgroup of patients most likely to benefit from prophylactic cranial irradiation (9 to 14%) includes patients who are likely to have an isolated CNS failure, but this had yet to be demonstrated. The toxicity of treatment is difficult to be influenced. Prophylactic cranial irradiation should not be given concurrently with chemotherapy, a larger interval after chemotherapy is indicated. The total dose should be in the range 30 to 36 Gy and the daily fraction size not larger than 2 Gy. (orig.) [de

  6. Assessing appearance-related disturbances in HIV-infected men who have sex with men (MSM): psychometrics of the body change and distress questionnaire-short form (ABCD-SF).

    Science.gov (United States)

    Blashill, Aaron J; Wilson, Johannes M; Baker, Joshua S; Mayer, Kenneth H; Safren, Steven A

    2014-06-01

    Appearance-related disturbances are common among HIV-infected MSM; however, to date, there have been limited options in the valid assessment of this construct. The aim of the current study was to assess the structural, internal, and convergent validity of the assessment of body change distress questionnaire (ABCD) and its short version. Exploratory and confirmatory factor analyses indicated that both versions fit the data well. Four subfactors were revealed measuring the following body disturbance constructs: (1) negative affect about appearance, (2) HIV health-related outcomes and stigma, (3) eating and exercise confusion, and (4) ART non-adherence. The subfactors and total scores revealed bivariate associations with salient health outcomes, including depressive symptoms, HIV sexual transmission risk behaviors, and ART non-adherence. The ABCD and its short form, offer valid means to assess varied aspects of body image disturbance among HIV-infected MSM, and require modest participant burden.

  7. Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum.

    Science.gov (United States)

    Ellis, Giovanina M; Huang, Sharon; Hitti, Jane; Frenkel, Lisa M

    2011-11-01

    Compare the risk of HIV drug resistance in women stopping suppressive nelfinavir (NFV)-based or Nevirapine (NVP)-based antiretroviral therapy (ART) after pregnancy. Specimens collected after stopping ART were tested for drug resistance by an oligonucleotide ligation assay and consensus sequencing. When postpartum drug resistance was detected, specimens obtained at study entry and during ART were evaluated. Sixteen of 38 women with ART-induced suppression of viral replication suspended ART postpartum. Resistance mutations were detected in 75% who stopped NFV-ART and in 50% who stopped NVP-ART. M184V, associated with Lamivudine resistance, was more frequent among those randomized to NFV-ART compared with NVP-ART (6 of 8 versus 1 of 8; P = 0.04), and nonnucleoside reverse transcriptase inhibitor resistance was detected in 4 of 8 stopping NVP-ART. HIV drug resistance was frequently observed among women who stopped suppressive NVP-ART or NFV-ART postpartum. This suggests that NFV-ART may have suboptimal potency, that staggering discontinuation of NVP-ART may be warranted, and/or ART adherence may be lax in women who choose to stop ART postpartum.

  8. Pregnancy loss and role of infant HIV status on perinatal mortality among HIV-infected women

    Directory of Open Access Journals (Sweden)

    Kim Hae-Young

    2012-08-01

    Full Text Available Abstract Background HIV-infected women, particularly those with advanced disease, may have higher rates of pregnancy loss (miscarriage and stillbirth and neonatal mortality than uninfected women. Here we examine risk factors for these adverse pregnancy outcomes in a cohort of HIV-infected women in Zambia considering the impact of infant HIV status. Methods A total of 1229 HIV-infected pregnant women were enrolled (2001–2004 in Lusaka, Zambia and followed to pregnancy outcome. Live-born infants were tested for HIV by PCR at birth, 1 week and 5 weeks. Obstetric and neonatal data were collected after delivery and the rates of neonatal ( Results The ratio of miscarriage and stillbirth per 100 live-births were 3.1 and 2.6, respectively. Higher maternal plasma viral load (adjusted odds ratio [AOR] for each log10 increase in HIV RNA copies/ml = 1.90; 95% confidence interval [CI] 1.10–3.27 and being symptomatic were associated with an increased risk of stillbirth (AOR = 3.19; 95% CI 1.46–6.97, and decreasing maternal CD4 count by 100 cells/mm3 with an increased risk of miscarriage (OR = 1.25; 95% CI 1.02–1.54. The neonatal mortality rate was 4.3 per 100 increasing to 6.3 by 70 days. Intrauterine HIV infection was not associated with neonatal morality but became associated with mortality through 70 days (adjusted hazard ratio = 2.76; 95% CI 1.25–6.08. Low birth weight and cessation of breastfeeding were significant risk factors for both neonatal and early mortality independent of infant HIV infection. Conclusions More advanced maternal HIV disease was associated with adverse pregnancy outcomes. Excess neonatal mortality in HIV-infected women was not primarily explained by infant HIV infection but was strongly associated with low birth weight and prematurity. Intrauterine HIV infection contributed to mortality as early as 70 days of infant age. Interventions to improve pregnancy outcomes for HIV-infected women are needed to

  9. Short message service reminder intervention doubles sexually transmitted infection/HIV re-testing rates among men who have sex with men.

    Science.gov (United States)

    Bourne, C; Knight, V; Guy, R; Wand, H; Lu, H; McNulty, A

    2011-04-01

    To evaluate the impact of a short message service (SMS) reminder system on HIV/sexually transmitted infection (STI) re-testing rates among men who have sex with men (MSM). The SMS reminder programme started in late 2008 at a large Australian sexual health clinic. SMS reminders were recommended 3-6 monthly for MSM considered high-risk based on self-reported sexual behaviour. The evaluation compared HIV negative MSM who had a HIV/STI test between 1 January and 31 August 2010 and received a SMS reminder (SMS group) with those tested in the same time period (comparison group) and pre-SMS period (pre-SMS group, 1 January 2008 and 31 August 2008) who did not receive the SMS. HIV/STI re-testing rates were measured within 9 months for each group. Baseline characteristics were compared between study groups and multivariate logistic regression used to assess the association between SMS and re-testing and control for any imbalances in the study groups. There were 714 HIV negative MSM in the SMS group, 1084 in the comparison group and 1753 in the pre-SMS group. In the SMS group, 64% were re-tested within 9 months compared to 30% in the comparison group (preminders increased HIV/STI re-testing among HIV negative MSM. SMS offers a cheap, efficient system to increase HIV/STI re-testing in a busy clinical setting.

  10. Sexual behavior, risk perception, and HIV transmission can respond to HIV antiviral drugs and vaccines through multiple pathways

    Science.gov (United States)

    Tully, Stephen; Cojocaru, Monica; Bauch, Chris T.

    2015-01-01

    There has been growing use of highly active antiretroviral treatment (HAART) for HIV and significant progress in developing prophylactic HIV vaccines. The simplest theories of counterproductive behavioral responses to such interventions tend to focus on single feedback mechanisms: for instance, HAART optimism makes infection less scary and thus promotes risky sexual behavior. Here, we develop an agent based, age-structured model of HIV transmission, risk perception, and partner selection in a core group to explore behavioral responses to interventions. We find that interventions can activate not one, but several feedback mechanisms that could potentially influence decision-making and HIV prevalence. In the model, HAART increases the attractiveness of unprotected sex, but it also increases perceived risk of infection and, on longer timescales, causes demographic impacts that partially counteract HAART optimism. Both HAART and vaccination usually lead to lower rates of unprotected sex on the whole, but intervention effectiveness depends strongly on whether individuals over- or under-estimate intervention coverage. Age-specific effects cause sexual behavior and HIV prevalence to change in opposite ways in old and young age groups. For complex infections like HIV—where interventions influence transmission, demography, sexual behavior and risk perception—we conclude that evaluations of behavioral responses should consider multiple feedback mechanisms. PMID:26507957

  11. Surgical site infection and timing of prophylactic antibiotics for appendectomy.

    Science.gov (United States)

    Wu, Wan-Ting; Tai, Feng-Chuan; Wang, Pa-Chun; Tsai, Ming-Lin

    2014-12-01

    Pre-operative prophylactic antibiotics may decrease the frequency of surgical site infection after appendectomy. However, the optimal timing for administration of pre-operative prophylactic antibiotics is unknown. The purpose of this study was to evaluate the effect of timing of prophylactic antibiotics on the frequency of surgical site infection after appendectomy. Medical records were reviewed retrospectively for 577 consecutive patients who had appendectomy for acute appendicitis from 2006 to 2009. Quality assurance guidelines for timing of prophylactic antibiotics before the skin incision were changed from 0 to 30 min before the skin incision (before June 2008) to 30 to 60 min before the skin incision (after June 2008). Surgical site infection occurred in 28 patients (4.9%). There was no difference in frequency of surgical site infection with different timing of pre-operative prophylactic antibiotic (pre-operative time 0 to 30 min: 9 infections [3.6%]; 31 to 60 min: 13 infections [5.4%]; 61 to 120 min: 5 infections [7.0%]; >120 min: 1 infection [6.6%]). Multivariable analysis showed that surgical site infection was associated significantly with medical comorbidity but not perforated appendicitis. The frequency of surgical site infection was independent of timing of preoperative prophylactic antibiotics but was associated with the presence of medical comorbidity.

  12. Short-course chemotherapy for paediatric respiratory tuberculosis: 5-year report.

    Science.gov (United States)

    Swaminathan, S; Raghavan, A; Duraipandian, M; Kripasankar, A S; Ramachandran, P

    2005-06-01

    This report presents the 5-year follow-up of 137 children with respiratory tuberculosis enrolled in a randomised clinical trial of two different anti-tuberculosis regimens 9HR and 2HRZ3/4RH2. Both regimens had similar cure rates, with low relapse rates and mortality. Of 134 children followed up to 5 years, 86% had normal radiographs, with more sequelae in the 9HR group (15% vs. 1.5%, P < 0.01). One patient relapsed and there was one accidental death. Short-course chemotherapy in children is safe, effective and well tolerated, and leads to excellent long-term results, with a small proportion of children left with radiological sequelae.

  13. The influence of ART on the treatment of Trichomonas vaginalis among HIV-infected women.

    Science.gov (United States)

    Adamski, Alys; Clark, Rebecca A; Mena, Leandro; Henderson, Harold; Levison, Judy; Schmidt, Norine; Gebrekristos, Hirut T; Martin, David H; Kissinger, Patricia

    2014-09-15

    Among women who are human immunodeficiency virus positive (HIV+), both prevalent and persistent infections with Trichomonas vaginalis (TV) are common. TV has been shown to increase vaginal shedding of HIV, which may influence HIV sexual and perinatal transmission, making prevention important. In 1 cohort of HIV+ women in Kenya, antiretroviral therapy (ART) use, mostly nevirapine based, was associated with lower cure rates of TV for single-dose therapy. Our goal was to repeat this study in a US-based cohort of HIV+/TV+ women and compare outcomes to those with multidose therapy. A secondary data analysis was performed on a multicentered cohort of HIV+/TV+ women who were randomized to single-dose (2 grams) or 7-day (500 mg twice daily) multidose metronidazole (MTZ) treatment. Test of cure visit, via culture, occurred 6-12 days after treatment completion. Information was collected on sex partner treatment and sexual exposures. Persistent TV infection rates were compared for women on ART at baseline vs not on ART. Of the 226 women included, those on ART had more treatment failures than women not on ART (24/146 [16.4%] vs 5/80 [6.3%]; P = .03). When stratified by treatment arm, more treatment failures were seen in the single-dose arm (17/73 [23.3%] vs 3/39 [7.7%]; P = .05) than in the multidose arm (7/73 [9.6%] vs 2/41 [4.8%]; P = .39). ART usage was associated with a higher TV persistent infection rate among those receiving the single-dose treatment, but not the multidose, providing more evidence that multidose should be the preferred treatment for HIV+ women. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

    Science.gov (United States)

    Eshleman, Susan H; Laeyendecker, Oliver; Parkin, Neil; Huang, Wei; Chappey, Colombe; Paquet, Agnes C; Serwadda, David; Reynolds, Steven J; Kiwanuka, Noah; Quinn, Thomas C; Gray, Ronald; Wawer, Maria

    2009-04-27

    To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment. Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA). Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hypersusceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase. Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B

  15. Synthesis and biological properties of novel 2-aminopyrimidin-4(3H)-ones highly potent against HIV-1 mutant strains.

    Science.gov (United States)

    Mai, Antonello; Artico, Marino; Rotili, Dante; Tarantino, Domenico; Clotet-Codina, Imma; Armand-Ugón, Mercedes; Ragno, Rino; Simeoni, Silvia; Sbardella, Gianluca; Nawrozkij, Maxim B; Samuele, Alberta; Maga, Giovanni; Esté, José A

    2007-11-01

    Following the disclosure of dihydro-alkoxy-, dihydro-alkylthio-, and dihydro-alkylamino-benzyl-oxopyrimidines (DABOs, S-DABOs, and NH-DABOs) as potent and selective anti-HIV-1 agents belonging to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, we report here the synthesis and biological evaluation of a novel series of DABOs bearing a N,N-disubstituted amino group or a cyclic amine at the pyrimidine-C2 position, a hydrogen atom or a small alkyl group at C5 and/or at the benzylic position, and the favorable 2,6-difluorobenzyl moiety at the C6 position (F2-N,N-DABOs). The new compounds were highly active up to the subnanomolar level against both wt HIV-1 and the Y181C mutant and at the submicromolar to nanomolar range against the K103N and Y188L mutant strains. Such derivatives were more potent than S-DABOs, NH-DABOs, and nevirapine and efavirenz were chosen as reference drugs. The higher inhibitor adaptability to the HIV-1 RT non-nucleoside binding site (NNBS) may account for the higher inhibitory effect exerted by the new molecules against the mutated RTs.

  16. Prophylactic antibiotics versus post- operative antibiotics in herniorraphy

    Directory of Open Access Journals (Sweden)

    Abedulla Khan Kayamkani

    2015-07-01

    Full Text Available Postoperative surgical site infections are a major source of illness.  Infection results in longer hospital stay and higher costs.  Uses of preoperative antibiotics have been standardized and are being used routinely in most clinical surgeries and include controversial areas like breast surgery and herniorraphy. Objective of the study is to find out the benefit of prophylactic use of antibiotics in the management of herniorraphy.This project was carried out in a multispeciality tertiary care teaching hospital from 1st-30th April in 2002. Group 1 patients were treated prophylactically half an hour before surgery with single dose of I.V. antibiotics (injection.  Ampicillin 1gm + injection.  Gentamicin 80mg. Group 2 patients were treated post surgery with capsule. Ampicillin 500mg 4 times a day for 7 days and injection. Gentamicin twice a day for first 4 days. In case of group 1 patients only one out of 20 patients (5% was infected.  Whereas in-group 2 patients 5 out of 20 patients (25% were infected. The cost of prophylactic antibiotic treatment was Rs. 25.56 per patient.  The postoperative antibiotic treatment cost was Rs. 220.4 per patient.  That means postoperative treatment is around 8.62 times costlier than prophylactic treatment.             From this study it is evident that prophylactic (preoperative treatment is better than postoperative treatment with antibiotics.

  17. The natural history of HIV infection

    DEFF Research Database (Denmark)

    Sabin, C.A.; Lundgren, J.D.

    2013-01-01

    PURPOSE OF REVIEW: To review recent published literature around three areas: long-term nonprogression/viral control; predictors of viral load set point/disease progression; and the potential impact of antiretroviral therapy (ART) in early HIV infection. RECENT FINDINGS: The natural course...... of untreated HIV infection varies widely with some HIV-positive individuals able to maintain high CD4 cell counts and/or suppressed viral load in the absence of ART. Although similar, the underlying mechanistic processes leading to long-term nonprogression and viral control are likely to differ. Concerted...... the immunological deterioration which would otherwise be seen in untreated HIV infection, recent studies do not address the longer term clinical benefits of ART at this very early stage. SUMMARY: A better understanding of the relative influences of viral, host, and environmental factors on the natural course of HIV...

  18. Do prophylactic antibiotics in gynecologic surgery prevent postoperative inflammatory complications? A systematic review.

    Science.gov (United States)

    Boesch, Cedric Emanuel; Pronk, Roderick Franziskus; Medved, Fabian; Hentschel, Pascal; Schaller, Hans-Eberhard; Umek, Wolfgang

    2017-06-01

    The aim of this study was to systematically review the literature on antibiotic prophylaxis in gynaecologic surgeries to prevent inflammatory complications after gynaecological operations. The study was carried out as a systematic review. Only randomised controlled trials of women undergoing gynaecological surgery were included. The Medline and the Cochrane library databases were searched from 1966 to 2016. The trials must have investigated an antibiotic intervention to prevent an inflammatory complication after gynaecological surgery. Trials were excluded if they were not randomised, uncontrolled or included obstetrical surgery. Prophylactic antibiotics prevent inflammatory complications after gynaecological surgery. Prophylactic antibiotics are more effective in surgery requiring access to the peritoneal cavity or the vagina. Cefotetan appears to be more capable in preventing the overall inflammatory complication rate than cefoxitin or cefazolin. No benefit has been shown for the combination of antibiotics as prophylaxis. No difference has been shown between the long-term and short-term use of antibiotics. There is no need for the primary use of an anaerobic antibacterial agent. Antibiotics help to prevent postoperative inflammatory complications after major gynecologic surgeries.

  19. Integration of prevention of mother-to-child transmission of HIV (PMTCT postpartum services with other HIV care and treatment services within the maternal and child health setting in Zimbabwe, 2012.

    Directory of Open Access Journals (Sweden)

    Katherine Wiegert

    Full Text Available We assessed the integration of PMTCT services during the postpartum period including early infant diagnosis of HIV (EID and adult and pediatric antiretroviral therapy (ART in maternal and child health (MCH facilities in Zimbabwe.From August to December 2012 we conducted a cross-sectional survey of a nationally representative sample of 151 MCH facilities. A questionnaire was used to survey each site about staff training, dried blood spot sample (DBS collection, turnaround time (TAT for test results, PMTCT services, and HIV care and treatment linkages for HIV-infected mothers and children and HIV-exposed infants. Descriptive analyses were used. Of the facilities surveyed, all facilities were trained on DBS collection and 92% responded. Approximately, 99% of responding facilities reported providing DBS collection and a basic HIV-exposed infant service package including EID, extended nevirapine prophylaxis, and use of cotrimoxazole. DBS collection was integrated with immunisations at 83% of facilities, CD4 testing with point-of-care machines was available at 37% of facilities, and ART for both mothers and children was provided at 27% of facilities. More than 80% of facilities reported that DBS test results take >4 weeks to return; TAT did not have a direct association with any specific type of transport, distance to the lab, or intermediate stops for data to travel.Zimbabwe has successfully scaled up and integrated the national EID and PMTCT programs into the existing MCH setting. The long TAT of infant DBS test results and the lack of integrated ART programs in the MCH setting could reduce effectiveness of the national PMTCT and ART programs. Addressing these important gaps will support successful implementation of the 2014 Zimbabwe's PMTCT guidelines under which all HIV-infected pregnant and breastfeeding women will be offered life-long ART and decentralized ART care.

  20. Evaluating the impact of tuberculosis control: number of deaths prevented by short-course chemotherapy in China

    CSIR Research Space (South Africa)

    Dye, C

    2000-06-01

    Full Text Available Tuberculosis (TB) is still amongst the most important causes of human morbidity and mortality killing approximately two million people each year. Standard short-course chemotherapy (SSCC) can rapidly control illness and dramatically reduce...

  1. Estimating effectiveness in HIV prevention trials with a Bayesian hierarchical compound Poisson frailty model

    Science.gov (United States)

    Coley, Rebecca Yates; Browna, Elizabeth R.

    2016-01-01

    Inconsistent results in recent HIV prevention trials of pre-exposure prophylactic interventions may be due to heterogeneity in risk among study participants. Intervention effectiveness is most commonly estimated with the Cox model, which compares event times between populations. When heterogeneity is present, this population-level measure underestimates intervention effectiveness for individuals who are at risk. We propose a likelihood-based Bayesian hierarchical model that estimates the individual-level effectiveness of candidate interventions by accounting for heterogeneity in risk with a compound Poisson-distributed frailty term. This model reflects the mechanisms of HIV risk and allows that some participants are not exposed to HIV and, therefore, have no risk of seroconversion during the study. We assess model performance via simulation and apply the model to data from an HIV prevention trial. PMID:26869051

  2. Palliative Short-Course Radiation Therapy in Rectal Cancer: A Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Picardi, Vincenzo; Deodato, Francesco [Department of Radiotherapy, Fondazione di Ricerca e Cura “Giovanni Paolo II,” Campobasso (Italy); Guido, Alessandra; Giaccherini, Lucia [Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna (Italy); Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it [Department of Radiotherapy, Fondazione di Ricerca e Cura “Giovanni Paolo II,” Campobasso (Italy); Frazzoni, Leonardo; Farioli, Andrea; Cuicchi, Dajana [Department of Medical and Surgical Sciences, University of Bologna, Bologna (Italy); Cilla, Savino [Department of Radiotherapy, Fondazione di Ricerca e Cura “Giovanni Paolo II,” Campobasso (Italy); Cellini, Francesco [Radiation Oncology Department, Policlinico Universitario Campus Bio-Medico, Rome (Italy); Uddin, A.F.M. Kamal [Department of Radiation Oncology, United Hospital Limited, Dhaka (Bangladesh); Gambacorta, Maria Antonietta [Department of Radiotherapy, Policlinico Universitario “A. Gemelli,” Università Cattolica del Sacro Cuore, Rome (Italy); Buwenge, Milly [Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna (Italy); Ardizzoni, Andrea [Medical Oncology Unit, Azienda Ospedaliera Universitaria, Policlinico S. Orsola-Malpighi, Bologna (Italy); Poggioli, Gilberto [Department of Medical and Surgical Sciences, University of Bologna, Bologna (Italy); Valentini, Vincenzo [Department of Radiotherapy, Policlinico Universitario “A. Gemelli,” Università Cattolica del Sacro Cuore, Rome (Italy); and others

    2016-07-15

    Purpose: The management of patients with symptomatic rectal cancer not amenable to curative treatment may be challenging. The aim of this phase 2 study was to evaluate the efficacy of short-course radiation therapy in patients with obstructing rectal cancer. Methods and Materials: Patients who were not candidates for surgical resection because of synchronous metastases, age, and/or comorbidities were considered eligible. The sample size was calculated based on the 2-stage design of Simon. Short-course radiation therapy was delivered with an isocentric 4-field box technique (total, 25 Gy; 5 fractions in 5 days). Chemotherapy was suspended during radiation treatment. Clinical outcome measures were symptomatic response rate, toxicity, colostomy-free survival, and overall survival. Results: From October 2003 to November 2012, 18 patients (median age, 77.5 years) were enrolled. The median follow-up was 11.5 months (range, 3-36 months). Four weeks after treatment, a complete response (ie, complete symptom resolution) was observed in 38.9% of patients and a partial response in 50.0% cases, whereas 11.1% had no response. The rates of reduction or resolution of pain and bleeding were 87.5% and 100%, respectively. The 1-, 2-, and 3-year colostomy-free survival rates were 100%, 71.4%, and 47.6%, respectively (median, 30 months). The 1-, 2-, and 3-year cumulative overall survival rates were 85.2%, 53%, and 39.8%, respectively (median, 25 months). No patients stopped treatment because of gastrointestinal or genitourinary toxicities: 38.9% of patients had grade 1 to 2 toxicity, and 16.7% had grade 3 toxicity. Only 1 patient had hematologic grade 2 toxicity, and 2 patients had grade 2 skin toxicity. Conclusions: Short-course radiation therapy may represent a safe and effective alternative treatment option in patients with obstructing rectal cancer not eligible for curative treatment, allowing colostomy to be avoided in a substantial proportion of patients.

  3. "They call our children 'Nevirapine Babies'"

    DEFF Research Database (Denmark)

    Østergaard, Lise Rosendal; Bula, Agatha

    2010-01-01

    Infant feeding is estimated to be responsible for 5%-20% of the burden of HIV transmission from mother to child. HIV positive women who cannot afford safe formula feeding are advised to practise exclusive breastfeeding (EBF) followed by prompt weaning. We conducted a qualitative study using...... as well as on EBF but much less knowledge on basic facts about breastfeeding. Despite their inten-tions less than half of the interviewed women managed to practice EBF and the barriers were explained by perceived lack of milk, lack of control over the feeding situation, felt and enacted stigma as well...

  4. Safety and adverse events of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) for rectal cancer

    International Nuclear Information System (INIS)

    Doi, Hiroshi; Kamikonya, Norihiko; Hirota, Shozo; Beppu, Naohito; Yanagi, Hidenori

    2014-01-01

    We presented good tolerability and short-term outcomes of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART; 25 Gy in 10 fractions for 5 days) combined with chemotherapy in a total of 73 patients with lower rectal cancer. Age, gender, tumor differentiation, and the type of surgery seemed to have no apparent effects on toxicity of SC-HART. SC-HART appeared to have a good feasibility for use in further clinical trials. (author)

  5. High HIV-1 Diversity and Prevalence of Transmitted Drug Resistance Among Antiretroviral-Naive HIV-Infected Pregnant Women from Rio de Janeiro, Brazil.

    Science.gov (United States)

    Delatorre, Edson; Silva-de-Jesus, Carlos; Couto-Fernandez, José Carlos; Pilotto, Jose H; Morgado, Mariza G

    2017-01-01

    Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infection may reduce the efficacy of prophylactic therapy to prevent mother-to-child transmission (PMTCT) and future treatment options. This study evaluated the diversity and the prevalence of transmitted drug resistance (TDR) in protease (PR) and reverse transcriptase (RT) regions of HIV-1 pol gene among 87 ARV-naive HIV-1-infected pregnant women from Rio de Janeiro, Brazil, between 2012 and 2015. The viral diversity comprised HIV-1 subtypes B (67.8%), F1 (17.2%), and C (4.6%); the circulating recombinant forms 12_BF (2.3%), 28/29_BF, 39_BF, 02_AG (1.1% each) and unique recombinants forms (4.5%). The overall prevalence of any TDR was 17.2%, of which 5.7% for nucleoside RT inhibitors, 5.7% for non-nucleoside RT inhibitors, and 8% for PR inhibitors. The TDR prevalence found in this population may affect the virological outcome of the standard PMTCT ARV-regimens, reinforcing the importance of continuous monitoring.

  6. Prophylactic versus therapeutic amnioinfusion for oligohydramnios in labour.

    Science.gov (United States)

    Novikova, Natalia; Hofmeyr, G Justus; Essilfie-Appiah, George

    2012-09-12

    Amnioinfusion aims to relieve umbilical cord compression during labour by infusing a liquid into the uterine cavity. The objective of this review was to assess the effects of prophylactic amnioinfusion for women in labour with oligohydramnios, but not fetal heart deceleration, compared with therapeutic amnioinfusion only if fetal heart rate decelerations or thick meconium-staining of the liquor occur. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2012). Randomised trials comparing prophylactic amnioinfusion in women in labour with oligohydramnios but not fetal heart rate deceleration in labour with therapeutic amnioinfusion. The authors assessed trial quality and extracted data. One randomized trial of 116 women was included. No differences were found in the rate of caesarean section (risk ratio 1.29, 95% confidence interval 0.60 to 2.74). There were no differences in cord arterial pH, oxytocin augmentation, neonatal pneumonia or postpartum endometritis. Prophylactic amnioinfusion was associated with increased intrapartum fever (risk ratio 3.48, 95% confidence interval 1.21 to 10.05). There appears to be no advantage of prophylactic amnioinfusion over therapeutic amnioinfusion carried out only when fetal heart rate decelerations or thick meconium-staining of the liquor occur.

  7. Estimating PMTCT's Impact on Heterosexual HIV Transmission: A Mathematical Modeling Analysis.

    Directory of Open Access Journals (Sweden)

    Aditya S Khanna

    Full Text Available Prevention of mother-to-child HIV transmission (PMTCT strategies include combined short-course antiretrovirals during pregnancy (Option A, triple-drug antiretroviral treament (ART during pregnancy and breastfeeding (Option B, or lifelong ART (Option B+. The WHO also recommends ART for HIV treatment and prevention of sexual transmission of HIV. The impact of PMTCT strategies on prevention of sexual HIV transmission of HIV is not known. We estimated the population-level impact of PMTCT interventions on heterosexual HIV transmission in southwestern Uganda and KwaZulu-Natal, South Africa, two regions with different HIV prevalence and fertility rates.We constructed and validated dynamic, stochastic, network-based HIV transmission models for each region. PMTCT Options A, B, and B+ were simulated over ten years under three scenarios: 1 current ART and PMTCT coverage, 2 current ART and high PMTCT coverage, and 3 high ART and PMTCT coverage. We compared adult HIV incidence after ten years of each intervention to Option A (and current ART at current coverage.At current coverage, Options B and B+ reduced heterosexual HIV incidence by about 5% and 15%, respectively, in both countries. With current ART and high PMTCT coverage, Option B+ reduced HIV incidence by 35% in Uganda and 19% in South Africa, while Option B had smaller, but meaningful, reductions. The greatest reductions in HIV incidence were achieved with high ART and PMTCT coverage. In this scenario, all PMTCT strategies yielded similar results.Implementation of Options B/B+ reduces adult HIV incidence, with greater effect (relative to Option A at current levels in Uganda than South Africa. These results are likely driven by Uganda's higher fertility rates.

  8. HIV vaccines: new frontiers in vaccine development.

    Science.gov (United States)

    Duerr, Ann; Wasserheit, Judith N; Corey, Lawrence

    2006-08-15

    A human immunodeficiency virus (HIV) vaccine is the most promising and feasible strategy to prevent the events during acute infection that simultaneously set the course of the epidemic in the community and the course of the disease for the individual. Because safety concerns limit the use of live, attenuated HIV and inactivated HIV, a variety of alternate approaches is being investigated. Traditional antibody-mediated approaches using recombinant HIV envelope proteins have shown no efficacy in 2 phase III trials. Current HIV vaccine trials are focusing primarily on cytotoxic T lymphocyte-mediated products that use viral vectors, either alone or as boosts to DNA plasmids that contain viral genes. The most immunogenic of these products appear to be the recombinant adenovirus vector vaccines, 2 of which are now in advanced clinical development.

  9. Theoretical domains: a heuristic for teaching behavioral theory in HIV/STD prevention courses.

    Science.gov (United States)

    Dolcini, M Margaret; Canin, Lisa; Gandelman, Alice; Skolnik, Heidi

    2004-10-01

    The HIV/STD epidemics have broadened the need for better behavioral intervention programs and highlighted the importance of providing training in behavioral theory to frontline program practitioners. However, there is a lack of effective methods for teaching theoretical concepts to people who may not have a background in behavioral science. This article presents a solution to this challenge by introducing a new heuristic for teaching theory and for placing individual theories/models in a broader context. Using a broad framework, we identify five domains that influence behavior: risk appraisal, self-perceptions, emotions and arousal, relationships and social influence, and environmental and structural factors. Each domain is described, and a brief overview of supporting literature is provided. Following the presentation of domains, we discuss course structure and activities.

  10. A prospective randomized evaluation of the prophylactic use of low-dose dopamine in cancer patients receiving interleukin-2.

    Science.gov (United States)

    Cormier, J N; Hurst, R; Vasselli, J; Lee, D; Kim, C J; McKee, M; Venzon, D; White, D; Marincola, F M; Rosenberg, S A

    1997-07-01

    The administration of high-dose interleukin-2 (IL-2) causes tumor regression in 17-25% of patients with metastatic melanoma or renal cell carcinoma. Renal dysfunction is a common dose-limiting toxicity of IL-2 administration, limiting 26% of treatment cycles. We have conducted a prospective randomized trial to evaluate whether the prophylactic administration of low-dose dopamine (2 mg/kg/min) can minimize renal toxicity and thus affect the amount of IL-2 administered. Forty-two patients were randomly assigned to receive systemic high-dose IL-2 with standard supportive measures (group A = 21 patients) or with the addition of prophylactic dopamine (group B = 21 patients) at 2 mg/kg/min. For patients in group B, dopamine was instituted 1 h before the initiation of IL-2 administration and was discontinued 6-12 h after the maximum number of doses of IL-2 were given. There was no difference in the amount of IL-2 administered for each course of therapy for groups A and B. Despite differences in urine flow (milliliters per kilogram per day), fluid balance (liters per day), and overall weight gain, prophylactic low-dose dopamine did not significantly alter maximum plasma urea or creatinine levels in group B when compared with the control group (group A). The overall toxicity profile considering all grade 3 and 4 toxicities for patients in groups A and B was comparable. Thus, there is no evidence to support the routine use of prophylactic low-dose dopamine in patients receiving high-dose IL-2.

  11. Prophylactic and thermovision measurements of electric machines and equipment

    Energy Technology Data Exchange (ETDEWEB)

    Jedlicka, R; Brestovansky, L [Atomova Elektraren Bohunice, Jaslovske Bohunice (Slovakia)

    1997-12-31

    High-voltage measurements of generators, unit and service transformers and some significant motor drives used at a nuclear power plant are described in this paper. Thermovision measurements of electric machines and distribution systems are dealt with in the second part of the paper. Power electric equipment represent one of the most significant components of a nuclear power plant. Turbine mechanical energy is converted into the electrical energy within these equipment. Power generated by generators is transformed by transformers so that it can achieve appropriate parameters for both the transmission over the distribution system and the power plant service power supply. The service power supply switchboards and cables provide supply to motors and other consumers necessary for the nuclear power plant technological process. The whole complex of equipment has to be maintained in good technical conditions. It is necessary to make thermovision and prophylactic measurements to identify and verify the electric equipment technical condition. The mentioned measurements warn the operation staff in advance against both gradual deterioration of power connection contact resistances, i.e. power connections overheating, and the machine insulation systems condition deterioration. The operation staff try to prevent the electric equipment operation accidents by early removing the detected failures, thus, improving the nuclear safety. In order to provide the above-mentioned activities a special prophylactic measurement group was established at the NPP Bohunice in 1983. The group specialists make following types of measurements. 1. Prophylactic measurements of electric machines. Prophylactics of 220 MW generators and 6 MW service power generators; Prophylactics of both unit and service transformers and VHV bushings; Prophylactics of major 6 kV motor drives. 2. Thermovision measurements of current connections. (Abstract Truncated)

  12. Dynamic HIV-1 genetic recombination and genotypic drug resistance among treatment-experienced adults in northern Ghana.

    Science.gov (United States)

    Nii-Trebi, Nicholas Israel; Brandful, James Ashun Mensah; Ibe, Shiro; Sugiura, Wataru; Barnor, Jacob Samson; Bampoh, Patrick Owiredu; Yamaoka, Shoji; Matano, Tetsuro; Yoshimura, Kazuhisa; Ishikawa, Koichi; Ampofo, William Kwabena

    2017-11-01

    There have been hardly any reports on the human immunodeficiency virus type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral therapy (ART) was introduced over a decade ago. This study investigated prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART-experienced patients in Tamale, the capital of the Northern Region of Ghana. A cross-sectional study was carried out on HIV-infected adult patients receiving first-line ART. HIV viral load (VL) and CD4 + T-cell counts were measured. The pol gene sequences were analysed for genotypic resistance by an in-house HIV-1 drug-resistance test; the prevailing HIV-1 subtypes were analysed in detail.Results/Key findings. A total of 33 subjects were studied. Participants comprised 11 males (33.3 %) and 22 (66.7 %) females, with a median age of 34.5 years [interquartile range (IQR) 30.0-40.3]. The median duration on ART was 12 months (IQR 8.0-24). Of the 24 subjects successfully genotyped, 10 (41.7 %) viruses possessed at least one mutation conferring resistance to nucleoside or non-nucleoside reverse-transcriptase inhibitors (NRTIs/NNRTIs). Two-class drug resistance to NRTI and NNRTI was mostly detected (25 %, 6/24). The most frequent mutations were lamivudine-resistance M184V and efavirenz/nevirapine-resistance K103N. HIV-1 subtype CRF02_AG was predominant (79.2 %). Other HIV-1 subtypes detected were G (8.3 %), A3 (4.2 %) and importantly two (8.3 %) unique HIV-1 recombinant forms with CRF02_AG/A3 mosaic. HIV-1 shows high genetic diversity and on-going viral genetic recombination in the study region. Nearly 42 % of the patients studied harboured a drug-resistant virus. The study underscores the need for continued surveillance of HIV-1 subtype diversity; and of drug-resistance patterns to guide selection of second-line regimens in northern Ghana.

  13. Prophylactic use of octreotide for asparaginase-induced acute pancreatitis.

    Science.gov (United States)

    Sakaguchi, Sachi; Higa, Takeshi; Suzuki, Mitsuyoshi; Fujimura, Junya; Shimizu, Toshiaki

    2017-08-01

    In the present study, we sought to evaluate the prophylactic use of octreotide for asparaginase-induced acute pancreatitis. We reviewed the medical records of seven patients in two institutions who received prophylactic octreotide for re-administration of asparaginase after asparaginase-induced acute pancreatitis. Three patients completed asparaginase treatment without developing pancreatitis, and four experienced recurrence of pancreatitis. A literature search using PubMed identified four additional patients in whom asparaginase was successfully re-administered with octreotide. Prophylactic use of octreotide may, thus, be warranted for patients who would benefit from re-administration of asparaginase for cancer treatment; however, careful observation is needed to monitor for breakthrough recurrence of pancreatitis.

  14. Concomitant contraceptive implant and efavirenz use in women living with HIV: perspectives on current evidence and policy implications for family planning and HIV treatment guidelines.

    Science.gov (United States)

    Patel, Rena C; Morroni, Chelsea; Scarsi, Kimberly K; Sripipatana, Tabitha; Kiarie, James; Cohen, Craig R

    2017-05-11

    Preventing unintended pregnancies is important among all women, including those living with HIV. Increasing numbers of women, including HIV-positive women, choose progestin-containing subdermal implants, which are one of the most effective forms of contraception. However, drug-drug interactions between contraceptive hormones and efavirenz-based antiretroviral therapy (ART) may reduce implant effectiveness. We present four inter-related perspectives on this issue. First, as a case study, we discuss how limited data prompted country-level guidance against the use of implants among women concomitantly using efavirenz in South Africa and its subsequent negative effects on the use of implants in general. Second, we discuss the existing clinical data on this topic, including the observational study from Kenya showing women using implants plus efavirenz-based ART had three-fold higher rates of pregnancy than women using implants plus nevirapine-based ART. However, the higher rates of pregnancy in the implant plus efavirenz group were still lower than the pregnancy rates among women using common alternative contraceptive methods, such as injectables. Third, we discuss the four pharmacokinetic studies that show 50-70% reductions in plasma progestin concentrations in women concurrently using efavirenz-based ART as compared to women not on any ART. These pharmacokinetic studies provide the biologic basis for the clinical findings. Fourth, we discuss how data on this topic have marked implications for both family planning and HIV programmes and policies globally. This controversy underlines the importance of integrating family planning services into routine HIV care, counselling women appropriately on increased risk of pregnancy with concomitant implant and efavirenz use, and expanding contraceptive method mix for all women. As global access to ART expands, greater research is needed to explore implant effectiveness when used concomitantly with newer ART regimens. Data on how

  15. The prophylactic effect of valproate on glyceryltrinitrate induced migraine

    DEFF Research Database (Denmark)

    Tvedskov, Jesper Filtenborg; Thomsen, L L; Iversen, H K

    2004-01-01

    In this study the human glyceryltrinitrate (GTN) model of migraine was for the first time used to test the effect of a prophylactic drug. We chose to test valproate due to its well documented effect as a migraine prophylactic drug. Efficacy of this compound would support the usefulness of the mod...

  16. Prophylactic Interventions in Neonatology: How Do They Fare in Real Life?

    Science.gov (United States)

    Rolnitsky, Asaph; Lee, Shoo K; Piedbouf, Bruno; Harrison, Adele; Shah, Prakesh S

    2015-10-01

    This study aims to evaluate the association of prophylactic antenatal steroids, indomethacin, and phototherapy with extremely preterm infant outcomes in a pragmatic setting. Retrospective study of infants born at <28 weeks gestation and admitted to 26 Canadian Neonatal Network neonatal intensive care units between 2010 and 2012. Mortality, severe neurological injury, retinopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, nosocomial infection, and patent ductus arteriosus ligation rates were compared between infants who received antenatal steroids, prophylactic indomethacin, and/or prophylactic phototherapy and those who did not. Of 3,465 eligible infants, 2,900 (84%) received antenatal steroids, 269 (8%) prophylactic indomethacin, and 403 (12%) prophylactic phototherapy. Associations were observed between antenatal steroids and mortality (adjusted odds ration [aOR] 0.47 [0.33-0.66]) and severe neurological injury (aOR 0.60 [0.46-0.77]), indomethacin and ductus arteriosus ligations (aOR 0.52 [0.31-0.87]), but not severe neurological injury (aOR 1.12 [0.81-1.54]), but phototherapy was not associated with any of the neonatal outcomes despite reductions in bilirubin. Antenatal steroids were associated with reduced mortality and neurological injury, prophylactic indomethacin was not associated with reduction in neurological injury and phototherapy was not associated with any improvement in neonatal outcomes. In a pragmatic setting, outside randomized controlled trials, the effectiveness and safety of prophylactic interventions in extremely preterm neonates vary; ongoing monitoring is warranted. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Impact of a short biostatistics course on knowledge and performance of postgraduate scholars: Implications for training of African doctors and biomedical researchers.

    Science.gov (United States)

    Chima, S C; Nkwanyana, N M; Esterhuizen, T M

    2015-12-01

    This study was designed to evaluate the impact of a short biostatistics course on knowledge and performance of statistical analysis by biomedical researchers in Africa. It is recognized that knowledge of biostatistics is essential for understanding and interpretation of modern scientific literature and active participation in the global research enterprise. Unfortunately, it has been observed that basic education of African scholars may be deficient in applied mathematics including biostatistics. Forty university affiliated biomedical researchers from South Africa volunteered for a 4-day short-course where participants were exposed to lectures on descriptive and inferential biostatistics and practical training on using a statistical software package for data analysis. A quantitative questionnaire was used to evaluate participants' statistical knowledge and performance pre- and post-course. Changes in knowledge and performance were measured using objective and subjective criteria. Data from completed questionnaires were captured and analyzed using Statistical Package for Social Sciences. Participants' pre- and post-course data were compared using nonparametric Wilcoxon signed ranks tests for nonnormally distributed variables. A P researchers in this cohort and highlights the potential benefits of short-courses in biostatistics to improve the knowledge and skills of biomedical researchers and scholars in Africa.

  18. Short-course thrombolysis as the first line of therapy for cardiac valve thrombosis.

    Science.gov (United States)

    Manteiga, R; Carlos Souto, J; Altès, A; Mateo, J; Arís, A; Dominguez, J M; Borrás, X; Carreras, F; Fontcuberta, J

    1998-04-01

    To retrospectively evaluate the clinical and echocardiographic criteria of thrombolytic therapy for mechanical heart valve thrombosis. Nineteen consecutive patients with 22 instances of prosthetic heart valve thrombosis (14 mitral, 2 aortic, 3 tricuspid, and 3 pulmonary) were treated with short-course thrombolytic therapy as first option of treatment in absence of contraindications. The thrombolytic therapy protocol consisted of streptokinase (1,500,000 IU in 90 minutes) (n = 18) in one (n = 7) or two (n = 11) cycles or recombinant tissue-type plasminogen activator (100 mg in 90 minutes) (n = 4). Overall success was seen in 82%, immediate complete success in 59%, and partial success in 23%. Six patients without total response to thrombolytic therapy underwent surgery, and pannus was observed in 83%. Six patients showed complications: allergy, stroke, transient ischemic attack, coronary embolism, minor bleeding, and one death. At diagnosis, 10 patients evidenced atrial thrombus by transesophageal echocardiography, 3 of whom experienced peripheral embolism during thrombolysis. Four episodes of rethrombosis were observed (16%). The survivorship was 84% with a mean follow-up of 42.6 months. A short-course of thrombolytic therapy may be considered first-line therapy for prosthetic heart valve thrombosis. The risk of peripheral embolism may be evaluated for the presence of atrial thrombus by transesophageal echocardiography at diagnosis.

  19. Efficacy of prophylactic splenectomy for proximal advanced gastric cancer invading greater curvature.

    Science.gov (United States)

    Ohkura, Yu; Haruta, Shusuke; Shindoh, Junichi; Tanaka, Tsuyoshi; Ueno, Masaki; Udagawa, Harushi

    2017-05-25

    For proximal gastric cancer invading the greater curvature, concomitant splenectomy is frequently performed to secure the clearance of lymph node metastases. However, prognostic impact of prophylactic splenectomy remains unclear. The aim of this study was to clarify the oncological significance of prophylactic splenectomy for advanced proximal gastric cancer invading the greater curvature. Retrospective review of 108 patients who underwent total or subtotal gastrectomy for advanced proximal gastric cancer involving the greater curvature was performed. Short-term and long-term outcomes were compared between the patients who underwent splenectomy (n = 63) and those who did not (n = 45). Patients who underwent splenectomy showed higher amount of blood loss (538 vs. 450 mL, p = 0.016) and morbidity rate (30.2 vs. 13.3, p = 0.041) compared with those who did not undergo splenectomy. In particular, pancreas-related complications were frequently observed among patients who received splenectomy (17.4 vs. 0%, p = 0.003). However, no significant improvement of long-term outcomes were confirmed in the cases with splenectomy (5-year recurrence-free rate, 60.2 vs. 67.3%; p = 0.609 and 5-year overall survival rates, 63.7 vs. 73.6%; p = 0.769). On the other hand, splenectomy was correlated with marginally better survival in patients with Borrmann type 1 or 2 gastric cancer (p = 0.072). For advanced proximal gastric cancer involving the greater curvature, prophylactic splenectomy may have no significant prognostic impact despite the increased morbidity rate after surgery. Such surgical procedure should be avoided as long as lymph node involvement is not evident.

  20. Innovative Training of In-Service Teachers for Active Learning: A Short Teacher Development Course Based on Physics Education Research

    Science.gov (United States)

    Zavala, Genaro; Alarcon, Hugo; Benegas, Julio

    2007-01-01

    In this contribution we describe a short development course for in-service physics teachers. The course structure and materials are based on the results of educational research, and its main objective is to provide in-service teachers with a first contact with the active learning strategy "Tutorials in Introductory Physics," developed by…

  1. Cost analysis of prophylactic intraoperative cystoscopic ureteral stents in gynecologic surgery.

    Science.gov (United States)

    Fanning, James; Fenton, Bradford; Jean, Geraldine Marie; Chae, Clara

    2011-12-01

    Prophylactic intraoperative ureteral stent placement is performed to decrease operative ureteric injury, though few data are available on the effectiveness of this procedure, and no data are available on its cost. To analyze the cost of prophylactic intraoperative cystoscopic ureteral stents in gynecologic surgery. All cases of prophylactic ureteral stent placement performed in gynecologic surgery during a 1-year period were identified and retrospectively reviewed through the electronic medical records database of Summa Health System. Costs were obtained through the Healthcare Cost Accounting System. The principles of cost-effective analysis were used (ie, explicit and detailed descriptions of costs and cost-effectiveness statistics). Importantly, we evaluated cost and not charges or financial model estimates. In addition, we obtained the contribution margins (ie, the hospital's net profit or loss) for prophylactic ureteral stent placement. Other gynecologic procedures were also analyzed. Among 792 major inpatient gynecologic procedures, 18 cases of prophylactic intraoperative ureteral stents were identified. Median costs were as follows: additional cost of prophylactic intraoperative ureteral stenting, $1580; additional cost of surgical resources, $770; cost of ureteral catheters, $427; cost of surgeons, $383. The contribution margins per case for various gynecologic surgical procedures were as follows: oophorectomy, $2804 profit; abdominal hysterectomy, $2649 profit; laparoscopically assisted vaginal hysterectomy (LAVH), $1760 profit. When intraoperative ureteral stenting was added, the contribution margins changed to the following: oophorectomy, $782 profit; abdominal hysterectomy, $627 profit; LAVH, $262 loss. Overall, the contribution margin profit was decreased by about 85%, from $2400 to $380. Prophylactic intraoperative ureteral stenting in gynecologic surgery decreases a hospital's contribution margin. Because of the expense of this procedure, as well as

  2. In vitro assessment of competitive and time-dependent inhibition of the nevirapine metabolism by nortriptyline in rats.

    Science.gov (United States)

    Usach, Iris; Ferrer, José-Maria; Peris, José-Esteban

    2018-04-17

    Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) widely used as a component of High Active Antiretroviral Therapy (HAART) since it is inexpensive, readily absorbed after oral administration and non-teratogenic. In the present work, the mechanism of a previously described pharmacokinetic interaction between NVP and the antidepressant drug nortriptyline (NT) was studied using rat hepatic microsomes. The obtained results showed a competitive inhibition of the NVP metabolism by NT. The three main NVP metabolites (2-OH-NVP, 3-OH-NVP and 12-OH-NVP) where competitively inhibited with similar inhibitory constant values (K i  = 4.01, 3.97 and 4.40 μM, respectively). Time-dependent inhibition of the NVP metabolism was also detected, with a 2.5-fold reduction in the IC 50 values of NT for 2-, 3-, and 12-OH-NVP formation when NT was preincubated with the microsomal suspension in the presence of an NADPH-generating system. A concentration-dependent inhibition of the formation of NVP metabolites by the main NT metabolite (10-OH-NT) was also observed, however, the inhibitory potency of 10-OH-NT was much lower than that of the parent drug. The apparent hepatic intrinsic clearance of NVP determined in these in vitro experiments was used to predict the in vivo clearance of NVP using the "well-stirred" and the "parallel-tube" models, resulting in values close to those previously observed in vivo clearance. Finally, a good prediction of the increase in the plasma concentrations of NVP when co-administered with NT was obtained employing the inhibitory constant of NT determined in vitro and the estimated plasma concentration of NT entering the liver. Copyright © 2018. Published by Elsevier Inc.

  3. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer – the RAPIDO trial

    International Nuclear Information System (INIS)

    Nilsson, Per J; Marijnen, Corrie AM; Nagtegaal, Iris D; Wiggers, Theo; Glimelius, Bengt; Etten, Boudewijn van; Hospers, Geke AP; Påhlman, Lars; Velde, Cornelis JH van de; Beets-Tan, Regina GH; Blomqvist, Lennart; Beukema, Jannet C; Kapiteijn, Ellen

    2013-01-01

    Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer. Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life. Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative

  4. Prophylactic treatment of migraine; the patient's view, a qualitative study

    NARCIS (Netherlands)

    Dekker, F.; Knuistingh Neven, A.; Andriesse, B.; Kernick, D.; Reis, R.; Ferrari, M.D.; Assendelft, W.J.J.

    2012-01-01

    BACKGROUND: Prophylactic treatment is an important but under-utilised option for the management of migraine. Patients and physicians appear to have reservations about initiating this treatment option. This paper explores the opinions, motives and expectations of patients regarding prophylactic

  5. CERN Technical Training 2004: New Short Courses (SC) on Microsoft Outlook

    CERN Multimedia

    Monique Duval

    2004-01-01

    The CERN Technical Training programme is now proposing a new format for courses on Microsoft Outlook. Three two-hours Short Courses (SC) will cover basic and advanced functionalities of the recommended mail client for email at CERN. Each module can be followed independently. The next scheduled sessions will take place as follows: Outlook (SC I): E-mail. Next session: 22.10.2004 (9h00-11h00) Outlook (SC II): Calendar, Tasks and Notes. Next session: 22.10.2004 (14h00-16h00) Outlook (SC III): Meetings and Delegation. Next session: 9.11.2004 (14h00-16h00) In particular, SC I will cover how to open, create and send email, work with attachments, use stationery, organise mail, and work with the address book, SC II will show how to work with the calendar, tasks and notes, and SC III will cover how to organise and manage meetings, work with meeting requests, share tasks, and use email and calendar delegation. The number of participants to each session is limited to 8. The instructor is English-French bilingual, and...

  6. Prophylactic and thermovision measurements of electric machines and equipment

    International Nuclear Information System (INIS)

    Jedlicka, R.; Brestovansky, L.

    1996-01-01

    High-voltage measurements of generators, unit and service transformers and some significant motor drives used at a nuclear power plant are described in this paper. Thermovision measurements of electric machines and distribution systems are dealt with in the second part of the paper. Power electric equipment represent one of the most significant components of a nuclear power plant. Turbine mechanical energy is converted into the electrical energy within these equipment. Power generated by generators is transformed by transformers so that it can achieve appropriate parameters for both the transmission over the distribution system and the power plant service power supply. The service power supply switchboards and cables provide supply to motors and other consumers necessary for the nuclear power plant technological process. The whole complex of equipment has to be maintained in good technical conditions. It is necessary to make thermovision and prophylactic measurements to identify and verify the electric equipment technical condition. The mentioned measurements warn the operation staff in advance against both gradual deterioration of power connection contact resistances, i.e. power connections overheating, and the machine insulation systems condition deterioration. The operation staff try to prevent the electric equipment operation accidents by early removing the detected failures, thus, improving the nuclear safety. In order to provide the above-mentioned activities a special prophylactic measurement group was established at the NPP Bohunice in 1983. The group specialists make following types of measurements. 1. Prophylactic measurements of electric machines. Prophylactics of 220 MW generators and 6 MW service power generators; Prophylactics of both unit and service transformers and VHV bushings; Prophylactics of major 6 kV motor drives. 2. Thermovision measurements of current connections. Measurements enumarated in paragraph 1 are made on disconnected electric

  7. Fostering Psychiatry in Ghana: The Impact of a Short Review Course through an International Collaboration

    Science.gov (United States)

    Laugharne, Jonathan; Appiah-Poku, John; Laugharne, Richard; Stanley, Susanne

    2011-01-01

    Objective: The aim of the current study was to evaluate a short review course in psychiatry conducted at the Kwame Nkrumah University of Science and Technology medical school and any change in student interest in a career in psychiatry. Method: Students were asked to complete a general psychiatric knowledge questionnaire before and immediately…

  8. In vitro resistance profile of the candidate HIV-1 microbicide drug dapivirine.

    Science.gov (United States)

    Schader, Susan M; Oliveira, Maureen; Ibanescu, Ruxandra-Ilinca; Moisi, Daniela; Colby-Germinario, Susan P; Wainberg, Mark A

    2012-02-01

    Antiretroviral-based microbicides may offer a means to reduce the sexual transmission of HIV-1. Suboptimal use of a microbicide may, however, lead to the development of drug resistance in users that are already, or become, infected with HIV-1. In such cases, the efficacy of treatments may be compromised since the same (or similar) antiretrovirals used in treatments are being developed as microbicides. To help predict which drug resistance mutations may develop in the context of suboptimal use, HIV-1 primary isolates of different subtypes and different baseline resistance profiles were used to infect primary cells in vitro in the presence of increasing suboptimal concentrations of the two candidate microbicide antiretrovirals dapivirine (DAP) and tenofovir (TFV) alone or in combination. Infections were ongoing for 25 weeks, after which reverse transcriptase genotypes were determined and scrutinized for the presence of any clinically recognized reverse transcriptase drug resistance mutations. Results indicated that suboptimal concentrations of DAP alone facilitated the emergence of common nonnucleoside reverse transcriptase inhibitor resistance mutations, while suboptimal concentrations of DAP plus TFV gave rise to fewer mutations. Suboptimal concentrations of TFV alone did not frequently result in the development of resistance mutations. Sensitivity evaluations for stavudine (d4T), nevirapine (NVP), and lamivudine (3TC) revealed that the selection of resistance as a consequence of suboptimal concentrations of DAP may compromise the potential for NVP to be used in treatment, a finding of potential relevance in developing countries.

  9. Feline immunodeficiency virus model for designing HIV/AIDS vaccines.

    Science.gov (United States)

    Yamamoto, Janet K; Sanou, Missa P; Abbott, Jeffrey R; Coleman, James K

    2010-01-01

    Feline immunodeficiency virus (FIV) discovered in 1986 is a lentivirus that causes AIDS in domestic cats. FIV is classified into five subtypes (A-E), and all subtypes and circulating intersubtype recombinants have been identified throughout the world. A commercial FIV vaccine, consisting of inactivated subtype-A and -D viruses (Fel-O-Vax FIV, Fort Dodge Animal Health), was released in the United States in 2002. The United States Department of Agriculture approved the commercial release of Fel-O-Vax FIV based on two efficacy trials using 105 laboratory cats and a major safety trial performed on 689 pet cats. The prototype and commercial FIV vaccines had broad prophylactic efficacy against global FIV subtypes and circulating intersubtype recombinants. The mechanisms of cross-subtype efficacy are attributed to FIV-specific T-cell immunity. Findings from these studies are being used to define the prophylactic epitopes needed for an HIV-1 vaccine for humans.

  10. In patients with a tumour invading the phrenic nerve does prophylactic diaphragm plication improve postoperative lung function?

    Science.gov (United States)

    Beattie, Gwyn W; Dunn, William G; Asif, Mohammed

    2016-09-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients with tumours involving the phrenic nerve, does prophylactic diaphragm plication improve lung function following tumour resection?' Using the reported search, 258 papers were found of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Three case reports and one case series represent 37 patients in the literature along with two relevant animal studies. Patients treated with prophylactic plication at the time of injury or sacrifice of the phrenic nerve had reduced radiological evidence of diaphragm paralysis, lower reported shortness of breath and reduced requirement for ventilatory support. In patients with prophylactic diaphragm plication and a concurrent pulmonary resection, the predicted postoperative lung function correlated closely with the postoperative measured FEV1, FVC and gas transfer. The postoperative measured FEV1 was reported as 86-98%, the FVC 82-89% and gas transfer 97% of the predicted values. Two animal models investigate the mechanics of respiration, spirometry and gas exchange following diaphragmatic plication. A randomized control study in four dogs measured a 50% reduction in tidal volume and respiratory rate, a 40% decrease in arterial PO2 and a 43% increase in arterial CO2 when the phrenic nerve was crushed in animals with a pneumonectomy but without prophylactic diaphragm plication. A further randomized control animal study with 28 dogs found that plicating the diaphragm after unilateral phrenic nerve transection resulted in a significant increase in tidal volume and lung compliance and a significant decrease in respiratory frequency and the work of breathing. Prophylactic diaphragm plication may preserve lung function, reduce the risk of

  11. A short course in quantum information theory. An approach from theoretical physics

    International Nuclear Information System (INIS)

    Diosi, L.

    2007-01-01

    This short and concise primer takes the vantage point of theoretical physics and the unity of physics. It sets out to strip the burgeoning field of quantum information science to its basics by linking it to universal concepts in physics. An extensive lecture rather than a comprehensive textbook, this volume is based on courses delivered over several years to advanced undergraduate and beginning graduate students, but essentially it addresses anyone with a working knowledge of basic quantum physics. Readers will find these lectures a most adequate entry point for theoretical studies in this field. (orig.)

  12. Short course on system safety analysis

    International Nuclear Information System (INIS)

    Sudmann, R.H.

    1992-01-01

    This course provides and introduction to methods generally used in safety analysis and accident investigation. It is a non-mathematical approach, directed toward a casual user. The participant will learn techniques allowing them to dissect a system or incident in order identify real or potential safety problems. These techniques will be applied to analyze events which have occurred within DOE facilities. As a manager or staff person with general oversight responsibilities, the participant should gain an awareness of the big picture and not just ''dig for facts.'' This can be accomplished by being alert and responsive to the atmosphere and condition of the plant; mood and impression of the worker and the behavioral climate. The techniques taught in the course can be used to identify critical areas or indicators. These indicators will signal problems before the ''facts'' will. Analysis techniques taught are used to gauge the breadth of the ''forest'' and not necessarily to identify the trees. For this course includes a technical background with experience in a chemical processing operations and a knowledge of basic chemistry and engineering is desirable. The course should help in a present or future assignment in an oversight role

  13. Maternal ability to take care of children exposed to HIV

    Directory of Open Access Journals (Sweden)

    Julyana Gomes Freitas

    2013-07-01

    Full Text Available OBJECTIVE: to assess the ability of mothers to take care of children exposed to HIV, using the Assessment Scale of Care Skills for Children Exposed to HIV at Birth and to check the association between the scale dimensions and maternal characteristics. METHOD: this cross-sectional study involved 62 HIV+ mothers whose children of up to one year old had been exposed to the virus at birth. The Assessment Scale of Care Skills for Children Exposed to HIV at Birth consists of 52 items and five dimensions, indicating high, moderate or low care ability. RESULTS: 72.7% of the mothers appropriately offered zidovudine syrup; 86.0% were highly skilled to prepare and administer milk formula; 44.4% were moderately able to prepare and administer complementary feeding; 76.5% revealed high ability to administer prophylactic treatment against pneumonia and 95.3% demonstrated high abilities for clinical monitoring and immunization. Significant associations were found between some maternal variables and the scale dimensions. CONCLUSION: the scale permits the assessment of maternal care delivery to these children and the accomplishment of specific child health interventions.

  14. Short course of radiation therapy in elderly patients with multiform glioblastoma

    International Nuclear Information System (INIS)

    Idbaih, A.; Taillibert, S.; Simon, J.M.; Lopez, S.; Lang, P.; Toubiana, T.; Feuvret, L.; Mazeron, J.J.; Idbaih, A.; Taillibert, S.; Psimaras, D.; Delattre, J.Y.; Schneble, H.M.

    2008-01-01

    Purpose: The optimal schedule of irradiation in elderly patients suffering from glioblastoma multiform (G.B.M.) is unsettled. Materials and methods: This study reviewed the charts of 28 consecutive G.B.M. patients aged 70 years or more with a Karnofsky Performance Status (K.P.S.) greater than or equal to 70 who received a short course of radiotherapy (40 grays in 15 fractions over three weeks). Results: The median age at surgery was 74.6 years (range, 70.1 - 85.7). No patient received prior or concomitant chemotherapy. The median progression-free survival and overall survival were 21.6 weeks (95% CI, 17.0 - 39.9) and 50.6 weeks (95% CI, 26.3 - 62.0), respectively. Even within a narrow range (< 90 or = 90), K.P.S. remained a prognostic factor (p = 0.03). Tolerance appeared acceptable in terms of K.P.S. changes and corticosteroid use during radiation therapy. Conclusion: These results support the efficacy of short schedule radiotherapy for G.B.M. in elderly patients with a good K.P.S.. (authors)

  15. Cardiac disturbances after pneumonectomy--the value of prophylactic digitalization.

    Science.gov (United States)

    Järvinen, A; Mattila, T; Appelqvist, P; Meurala, H; Mattila, S

    1978-01-01

    The incidence of postoperative cardiac disturbances and the value of prophylactic digitalization were studied retrospectively in 143 patients undergoing pneumonectomy for carcinoma of the lung. Cardiac arrhythmias occurred in 29% and tachycardia episodes in 30% of the patients. The incidence of myocardial infarction was 2%. Operative mortality was 4%. The cardiac disturbances developed more often after left than after right pneumonectomy. The age of the patients, a history of angina pectoris or hypertension did not markedly increase the incidence of cardiac disturbances, neither did operative factors, such as pericardiotomy, left atrial resection, major bleeding nor postoperative empyema. Prophylactic digitalization significantly reduced postoperative cardiac disorders, their frequency being 33% in the group of patients who received prophylactic digitalis compared with 65% in the group that did not.

  16. Course and Short-Term Outcomes of Separation Anxiety Disorder in a Community Sample of Twins.

    Science.gov (United States)

    Foley, Debra L.; Pickles, Andrew; Maes, Hermine M.; Silberg, Judy L.; Eaves, Lindon J.

    2004-01-01

    Objective: To assess the course and short-term outcomes associated with separation anxiety disorder (SAD) in a community setting. Method: The subjects were 161 of 2,061 8- to 17-year-old twins with SAD from a community-based twin study. Subjects were born between 1974 and 1983. Subjects and parents were personally interviewed about the subject's…

  17. Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy

    DEFF Research Database (Denmark)

    Filteau, Suzanne; PrayGod, George; Kasonka, Lackson

    2015-01-01

    BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study...... was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI)

  18. HIV prevalence and trends among pregnant women in Abuja, Nigeria

    African Journals Online (AJOL)

    HIV prevalence and trends among pregnant women in Abuja, Nigeria: a 5-year ... trends in HIV prevalence to ascertain the current course of the HIV epidemic in ... Objective: The aim of this study was to determine the prevalence of HIV and its ...

  19. [Prophylactic treatments of migraine].

    Science.gov (United States)

    Massiou, H

    2000-01-01

    Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks. It is usually proposed to patients who suffer from two or more attacks per month. It should also be considered in patients who suffer from less frequent, but prolonged, disabling attacks with a poor response to abortive treatment, and who consider that their quality of life is reduced between attacks. Excessive intake of acute medication, more than twice a week, is a strong indication for prophylactic treatment. In order to obtain a good compliance to treatment, the patient must be informed of the expected efficacy of the drugs, and of their most frequent side effects. Thus, the choice of a prophylactic drug is made together with the patient. Based on the results of published controlled trials, the main prophylactic drugs are some betablockers, methysergide, pizotifene, oxetorone, flunarizine, amitriptyline, NSAIDs, and sodium valproate. Some less evaluated drugs such as aspirin, DHE, indoramine, verapamil, may be useful. Other substances such as riboflavin and new antiepileptic dugs are being evaluated. The choice of the drug to start with depends on several considerations. The first step is to make sure that there are no contra indications, and no possible interaction with the abortive medications. Then, possible side effects will be taken into account, for example, weight gain is a problem for most young women and patients who practice sports may not tolerate betablockers. Associated pathologies have to be checked. For example, a hypertensive migraine sufferers may benefit from betablockers; in a patient who suffers both from migraine and tension type headaches or from depression, amitriptyline is the first choice drug. The type of migraine should also be considered; for instance, in frequent attacks with aura, aspirin is recommended and betablockers avoided. In most cases, prophylaxis should be given as monotherapy, and it is often necessary to try successively several drugs

  20. HIV/AIDS programmes should focus on improved access.

    Science.gov (United States)

    Manning, A

    2000-10-14

    This paper discusses the need for HIV/AIDS programs in sub-Saharan countries to focus more on improved access to information to empower poor people living in remote areas. It is noted that despite Glaxo Wellcome's move to reduce the cost of antiretroviral therapy, it is unlikely to have an impact on most of those infected with or affected by HIV/AIDS, since concerns regarding lack of sustainability, bureaucratic administration, and communication difficulties predominate in the country. In this regard, it is therefore recommended that national HIV/AIDS programs be balanced with the needs of both the community and the individual and in prevention and care. Health workers should be explicit in confronting traditional beliefs, such as those about gender roles and traditional medicine, in prevention campaigns. Moreover, there is also an urgent need to improve access to condoms; strengthen health programs such as directly observed treatment short-term (DOTS) courses for tuberculosis and the syndromic approach to sexually transmitted disease treatment; and improve practical support to communities caring for those who are sick and the orphans. Lastly, all partners working with prevention programs should use the more positive community attitudes towards HIV/AIDS issues seen in many sub-Saharan countries to develop evidence-based programs that focus more on improved access and less on sustainability.

  1. Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Markus Hecht

    Full Text Available Cancer prevention and therapy in HIV-1-infected patients will play an important role in future. The non-nucleoside reverse transcriptase inhibitors (NNRTI Efavirenz and Nevirapine are cytotoxic against cancer cells in vitro. As other NNRTIs have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo.Cytotoxicity was studied by Annexin-V-APC/7AAD staining and flow cytometry in the pancreatic cancer cell lines BxPC-3 and Panc-1 and confirmed by colony formation assays. The 50% effective cytotoxic concentrations (EC50 were calculated and compared to the blood levels in our patients and published data.The in vitro EC50 of the different drugs in the BxPC-3 pancreatic cancer cells were: Efavirenz 31.5 μmol/l (= 9944 ng/ml, Nevirapine 239 μmol/l (= 63,786 ng/ml, Etravirine 89.0 μmol/l (= 38,740 ng/ml, Lersivirine 543 μmol/l (= 168,523 ng/ml, Delavirdine 171 μmol/l (= 78,072 ng/ml, Rilpivirine 24.4 μmol/l (= 8941 ng/ml. As Efavirenz and Rilpivirine had the highest cytotoxic potential and Nevirapine is frequently used in HIV-1 positive patients, the results of these three drugs were further studied in Panc-1 pancreatic cancer cells and confirmed with colony formation assays. 205 patient blood levels of Efavirenz, 127 of Rilpivirine and 31 of Nevirapine were analyzed. The mean blood level of Efavirenz was 3587 ng/ml (range 162-15,363 ng/ml, of Rilpivirine 144 ng/ml (range 0-572 ng/ml and of Nevirapine 4955 ng/ml (range 1856-8697 ng/ml. Blood levels from our patients and from published data had comparable Efavirenz levels to the in vitro toxic EC50 in about 1 to 5% of all patients.All studied NNRTIs were toxic against cancer cells. A low percentage of patients taking Efavirenz reached in vitro cytotoxic blood levels. It can be speculated that in HIV-1 positive patients having high Efavirenz blood levels pancreatic

  2. Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

    Science.gov (United States)

    Parisi, Saverio Giuseppe; Basso, Monica; Mengoli, Carlo; Scaggiante, Renzo; Andreis, Samantha; Franzetti, Marzia Maria; Cattelan, Anna Maria; Zago, Daniela; Cruciani, Mario; Andreoni, Massimo; Piovesan, Sara; Palù, Giorgio; Alberti, Alfredo

    2017-01-01

    Background Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients. PMID:28845109

  3. CERN Technical Training 2004: New Short Courses (SC) on Microsoft Outlook

    CERN Multimedia

    Monique Duval

    2004-01-01

    The CERN Technical Training programme is now proposing a new format for courses on Microsoft Outlook. Three two-hours Short Courses (SC) will cover basic and advanced functionalities of the recommended mail client for email at CERN. Each module can be followed independently. The next scheduled sessions will take place as follows: Outlook (SC I): E-mail. Next session: 31.8.2004 (9h00-11h00) Outlook (SC II): Calendar, Tasks and Notes. Next session: 31.8.2004 (14h00-16h00) Outlook (SC III): Meetings and Delegation. Next session: 7.9.2004 (14h00-16h00) In particular, SC I will cover how to open, create and send email, work with attachments, use stationery, organise mail, and work with the address book, SC II will show how to work with the calendar, tasks and notes, and SC III will cover how to organise and manage meetings, work with meeting requests, share tasks, and use email and calendar delegation. The number of participants to each session is limited to 8. The instructor is English-French bilingual, and she...

  4. How to use sequence analysis for life course epidemiology? An example on HIV-positive Sub-Saharan migrants in France.

    Science.gov (United States)

    Gosselin, Anne; Desgrées du Loû, Annabel; Lelièvre, Eva

    2018-06-01

    Life course epidemiology is now an established field in social epidemiology; in sociodemography, the quantitative analysis of biographies recently experienced significant trend from event history analysis to sequence analysis. The purpose of this article is to introduce and adapt this methodology to a social epidemiology question, taking the example of the impact of HIV diagnosis on Sub-Saharan migrants' residential trajectories in the Paris region. The sample consists of 640 migrants born in Sub-Saharan Africa receiving HIV care. They were interviewed in healthcare facilities in the Paris region within the PARCOURS project, conducted from 2012 to 2013, using life event history calendars, which recorded year by year their health, family and residential histories. We introduce a two-step methodological approach consisting of (1) sequence analysis by optimal matching to build a typology of migrants' residential pathways before and after diagnosis, and (2) a Cox model of the probability to experience changes in the residential situation. The seven-clusters typology shows that for a majority, the HIV diagnosis did not entail changes in residential situation. However 30% of the migrants experienced a change in their residential situation at time of diagnosis. The Cox model analysis reveals that this residential change was in fact moving in with one's partner (HR 2.99, P<0.000) rather than network rejection. This original combination of sequence analysis and Cox models is a powerful process that could be applied to other themes and constitutes a new approach in the life course epidemiology toolbox. NCT02566148. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Prophylactic Antibiotics and Wound Infection

    OpenAIRE

    Elbur, Abubaker Ibrahim; M.A., Yousif; El-Sayed, Ahmed S.A.; Abdel-Rahman, Manar E.

    2013-01-01

    Introduction: Surgical site infections account for 14%-25% of all nosocomial infections. The main aims of this study were to audit the use of prophylactic antibiotic, to quantify the rate of post-operative wound infection, and to identify risk factors for its occurrence in general surgery.

  6. Engineering HIV-1-resistant T-cells from short-hairpin RNA-expressing hematopoietic stem/progenitor cells in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Gene-Errol E Ringpis

    Full Text Available Down-regulation of the HIV-1 coreceptor CCR5 holds significant potential for long-term protection against HIV-1 in patients. Using the humanized bone marrow/liver/thymus (hu-BLT mouse model which allows investigation of human hematopoietic stem/progenitor cell (HSPC transplant and immune system reconstitution as well as HIV-1 infection, we previously demonstrated stable inhibition of CCR5 expression in systemic lymphoid tissues via transplantation of HSPCs genetically modified by lentiviral vector transduction to express short hairpin RNA (shRNA. However, CCR5 down-regulation will not be effective against existing CXCR4-tropic HIV-1 and emergence of resistant viral strains. As such, combination approaches targeting additional steps in the virus lifecycle are required. We screened a panel of previously published shRNAs targeting highly conserved regions and identified a potent shRNA targeting the R-region of the HIV-1 long terminal repeat (LTR. Here, we report that human CD4(+ T-cells derived from transplanted HSPC engineered to co-express shRNAs targeting CCR5 and HIV-1 LTR are resistant to CCR5- and CXCR4- tropic HIV-1-mediated depletion in vivo. Transduction with the combination vector suppressed CXCR4- and CCR5- tropic viral replication in cell lines and peripheral blood mononuclear cells in vitro. No obvious cytotoxicity or interferon response was observed. Transplantation of combination vector-transduced HSPC into hu-BLT mice resulted in efficient engraftment and subsequent stable gene marking and CCR5 down-regulation in human CD4(+ T-cells within peripheral blood and systemic lymphoid tissues, including gut-associated lymphoid tissue, a major site of robust viral replication, for over twelve weeks. CXCR4- and CCR5- tropic HIV-1 infection was effectively inhibited in hu-BLT mouse spleen-derived human CD4(+ T-cells ex vivo. Furthermore, levels of gene-marked CD4(+ T-cells in peripheral blood increased despite systemic infection with either

  7. Impact of a five-day short course on integration of health promotion into practice in north Queensland.

    Science.gov (United States)

    Devine, Susan G; Llewellyn-Jones, Lorraine; Lloyd, Jacqui

    2009-04-01

    Workforce development is one element of health promotion capacity building. This paper describes the extent to which participants in a five-day short course in health promotion, delivered three times in north Queensland during 2007, reported greater adoption of health promotion within their work roles, and the factors that affected the level of adoption. Out of 54 course attendees, 39 completed a post-course survey five to nine months after completing the course (72% response rate). Additionally, 11 course attendees participated in a focus group or phone interview to explore survey findings. The courses succeeded in providing knowledge, skills, confidence and enthusiasm to undertake health promotion work. Eighty per cent of participants stated they had incorporated health promotion into their work frequently or all of the time since undertaking the course. Lack of understanding of health promotion from co-workers and managers, lack of organisational support and commitment, lack of resources, competing clinical priorities, and lack of time were cited as the main barriers for undertaking health promotion. The course met participant training needs. However, similar training across all levels of staff including management may help to develop organisational capacity, thereby building a more knowledgeable workforce that is supported to undertake health promotion as a core part of an organisation's business.

  8. Adaptation and validation of the short version WHOQOL-HIV in Ethiopia

    DEFF Research Database (Denmark)

    Tesfaye Woldeyohannes, Markos; Olsen, Mette Frahm; Medhin, Girmay

    2016-01-01

    BACKGROUND: Quality of life of patients is an important element in the evaluation of outcome of health care, social services and clinical trials. The WHOQOL instruments were originally developed for measurement of quality of life across cultures. However, there were concerns raised about the cross-cultural...... equivalence of the WHOQOL-HIV when used among people with HIV in Ethiopia. Therefore, this study aimed at adapting the WHOQOL-HIV bref for the Ethiopian setting. METHODS: A step-wise adaptation of the WHOQOL-HIV bref for use in Ethiopia was conducted to produce an Ethiopian version...... were recruited from HIV clinics. RESULTS: In the process of adaptation, new items of relevance to the context were added while seven items were deleted because of problems with acceptability and poor psychometric properties. The Cronbach's α for the final tool with twenty-seven items WHOQOL...

  9. CD41 T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa.

    Science.gov (United States)

    Geng, Elvin H; Neilands, Torsten B; Thièbaut, Rodolphe; Bwana, Mwebesa Bosco; Nash, Denis; Moore, Richard D; Wood, Robin; Zannou, Djimon Marcel; Althoff, Keri N; Lim, Poh Lian; Nachega, Jean B; Easterbrook, Philippa J; Kambugu, Andrew; Little, Francesca; Nakigozi, Gertrude; Nakanjako, Damalie; Kiggundu, Valerian; Ki Li, Patrick Chung; Bangsberg, David R; Fox, Matthew P; Prozesky, HansW; Hunt, Peter W; Davies, Mary-Ann; Reynolds, Steven J; Egger, Matthias; Yiannoutsos, Constantin T; Vittinghoff, Eric V; Deeks, Steven G; Martin, Jeffrey N

    2015-02-01

    Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/ml was 529/ml [95% confidence interval (CI): 517–541] in North America, 494/ml (95% CI: 429–559) in West Africa, 515/ml (95% CI: 508–522) in Southern Africa, 503/ml (95% CI: 478–528) in Asia and 437/ml (95% CI: 425–449) in East Africa. CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

  10. Inter-pregnancy interval and pregnancy outcomes among HIV ...

    African Journals Online (AJOL)

    owner

    Abstract Background: Both short and long inter-pregnancy intervals have been associated with higher risk of adverse pregnancy outcomes. More so, short inter- pregnancy interval among HIV- positive women implies higher birth rate and subsequently a higher number of neonates exposed to HIV and potentially at.

  11. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 4458 ... Vol 104, No 5 (2014), ABC – Advocates for Breast Cancer, Abstract PDF ... thinking in Souh African medical students - An empirical study, Abstract PDF ... of voluntary HIV testing and nevirapine to reduce mother-to-child ...

  12. Gene Therapy Targeting HIV Entry

    Directory of Open Access Journals (Sweden)

    Chuka Didigu

    2014-03-01

    Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

  13. Structural Insights into the Mechanisms of Action of Short-Peptide HIV-1 Fusion Inhibitors Targeting the Gp41 Pocket

    Directory of Open Access Journals (Sweden)

    Xiujuan Zhang

    2018-02-01

    Full Text Available The deep hydrophobic pocket of HIV-1 gp41 has been considered a drug target, but short-peptides targeting this site usually lack potent antiviral activity. By applying the M-T hook structure, we previously generated highly potent short-peptide fusion inhibitors that specifically targeted the pocket site, such as MT-SC22EK, HP23L, and LP-11. Here, the crystal structures of HP23L and LP-11 bound to the target mimic peptide N36 demonstrated the critical intrahelical and interhelical interactions, especially verifying that the hook-like conformation was finely adopted while the methionine residue was replaced by the oxidation-less prone residue leucine, and that addition of an extra glutamic acid significantly enhanced the binding and inhibitory activities. The structure of HP23L bound to N36 with two mutations (E49K and L57R revealed the critical residues and motifs mediating drug resistance and provided new insights into the mechanism of action of inhibitors. Therefore, the present data help our understanding for the structure-activity relationship (SAR of HIV-1 fusion inhibitors and facilitate the development of novel antiviral drugs.

  14. CO2 Sequestration short course

    Energy Technology Data Exchange (ETDEWEB)

    DePaolo, Donald J. [Lawrence Berkeley National Laboratory; Cole, David R [The Ohio State University; Navrotsky, Alexandra [University of California-Davis; Bourg, Ian C [Lawrence Berkeley National Laboratory

    2014-12-08

    Given the public’s interest and concern over the impact of atmospheric greenhouse gases (GHGs) on global warming and related climate change patterns, the course is a timely discussion of the underlying geochemical and mineralogical processes associated with gas-water-mineral-interactions encountered during geological sequestration of CO2. The geochemical and mineralogical processes encountered in the subsurface during storage of CO2 will play an important role in facilitating the isolation of anthropogenic CO2 in the subsurface for thousands of years, thus moderating rapid increases in concentrations of atmospheric CO2 and mitigating global warming. Successful implementation of a variety of geological sequestration scenarios will be dependent on our ability to accurately predict, monitor and verify the behavior of CO2 in the subsurface. The course was proposed to and accepted by the Mineralogical Society of America (MSA) and The Geochemical Society (GS).

  15. Low risk of perioperative infection without prophylactic antibiotics for transperineal prostate brachytherapy

    International Nuclear Information System (INIS)

    Wallner, Kent; Roy, Jitendra; Harrison, Louis

    1996-01-01

    Purpose: To determine the incidence of postimplant infection in patients who are not given prophylactic antibiotics (ATBs). Methods and Materials: One hundred thirty-one patients had computerized tomography (CT)-planned transperineal 125 I implantation of the prostate from 1988 through 1995. One hundred fourteen of the patients did not receive prophylactic ATBs, 19 of whom required postimplant Foley catheter drainage for 1 day or more for acute urinary retention. Results: The incidence of postimplant febrile episodes within 2 weeks of surgery among the patients who had not received prophylactic ATBs was 2 of 114 (2%). One of the two patients who developed postimplantation febrile episodes was treated successfully with ATBs as an outpatient. The second patient, who had a history of chronic lymphocytic leukemia (CLL) and immune suppression, developed E. coli sepsis and required intravenous antibiotics. Of 17 patients who received prophylactic ATBs, none had a postoperative febrile episode. Conclusion: We continue to refrain from routinely prescribing prophylactic ATBs unless there is some compelling circumstance including rheumatic heart disease, prosthetic devices, immune compromise, or a previous history of prostatitis

  16. AIDS activists take South African government to court.

    Science.gov (United States)

    Baleta, A

    2000-08-26

    In South Africa, AIDS activists are taking legal action against their government because of its refusal to provide HIV-positive women with drugs to prevent mother-to-child transmission of HIV. The Treatment Action Campaign gave the health department an ultimatum to make moves to change policy on treating infected mothers; however, since the department had not responded, the legal process was set to begin. Mark Heywood, the Campaign's spokesman, said that the campaign is pushing for the implementation of programs on a phased basis to provide zidovudine or nevirapine at facilities where it is possible. It is noted that the government has remained steadfast in its opposition to an expansion of the program to all HIV-positive women attending state health services. Although Health Minister Mantho Tshabalala Msimang said that the drug regulatory authority is reviewing results of studies on nevirapine use, with a view to possible registration of the drug, Heywood argues that such an action continues to question the efficacy of antiretrovirals since these tests have already been done.

  17. A Directed Molecular Evolution Approach to Improved Immunogenicity of the HIV-1 Envelope Glycoprotein

    Science.gov (United States)

    Du, Sean X.; Xu, Li; Zhang, Wenge; Tang, Susan; Boenig, Rebecca I.; Chen, Helen; Mariano, Ellaine B.; Zwick, Michael B.; Parren, Paul W. H. I.; Burton, Dennis R.; Wrin, Terri; Petropoulos, Christos J.; Ballantyne, John A.; Chambers, Michael; Whalen, Robert G.

    2011-01-01

    A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences. PMID:21738594

  18. Tandem bispecific broadly neutralizing antibody - a novel approach to HIV-1 treatment.

    Science.gov (United States)

    Ferrari, Guido

    2018-04-23

    The last decade has led to a significant advance in our knowledge of HIV-1 latency and immunity. However, we are still not close to finding a cure for HIV-1. Although combination antiretroviral therapy (cART) has led to increased survival, almost close to that of the general population, it is still not curative. In the current issue of the JCI, Wu et al. studied the prophylactic and therapeutic potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb), BiIA-SG. This bnAb's breadth and potency were highly effective in protection and treatment settings, as measured by complete viremia control following direct infusion, as well as elimination of infected cells and delay in viral rebound when delivered with a recombinant vector. These observations underscore the need for the clinical development of BiIA-SG for the prevention of HIV-1.

  19. Pregnancy and HIV infection

    Directory of Open Access Journals (Sweden)

    Mete Sucu

    2016-12-01

    Full Text Available The management of Human Immunodeficiency Virus (HIV infection is progressing rapidly. In developed countries, the perinatal transmission rates have decreased from 20-30% to 1-2% with the use of antiretroviral therapy and cesarean section. Interventions for the prevention of prenatal transmission has made the prenatal care of pregnant patients with HIV infection more complex. Rapid development of standard care and continuing increase in the distribution of HIV infection has required clinicians taking care of pregnants to have current information. Therefore, in our review we aimed to summarize the prenatal course, treatment and preventive methods for perinatal transmission of HIV. [Archives Medical Review Journal 2016; 25(4.000: 522-535

  20. The metabolic profiles of HIV-infected and non-infected women in ...

    African Journals Online (AJOL)

    infected and HIV-uninfected women. Conclusions: The results indicate a possible impact of HIV infection on serum protein and serum albumin, which may adversely affect biochemical nutritional status and the course of HIV progression.

  1. Prophylactic antidepressant treatment following acute coronary syndrome

    DEFF Research Database (Denmark)

    Christiansen, Ole G; Madsen, Michael T; Simonsen, Erik

    2017-01-01

    Major depressive disorder is significantly increased in patients following acute coronary syndrome resulting in twofold increased mortality compared with patients without depression. The depression diagnosis is often missed leading to considerable undertreatment. This systematic review assesses...... the current evidence of primary prophylactic treatment of depression in patients after acute coronary syndrome. The study protocol was prospectively registered at PROSPERO (registration number CRD42015025587). A systematic review were conducted and reported according to Preferred Reporting Items...... for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, PsychINFO, CINAHL, and Cochran Library was searched. Two independent reviewers screened the records. The inclusion criteria were randomized controlled trials on adult patients with acute coronary syndrome treated prophylactically...

  2. Short-term Mobility and Increased Partnership Concurrency among Men in Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Susan Cassels

    Full Text Available Migration has long been understood as an underlying factor for HIV transmission, and sexual partner concurrency has been increasingly studied as an important component of HIV transmission dynamics. However, less work has examined the role of short-term mobility in sexual partner concurrency using a network approach. Short-term mobility may be a risk for HIV for the migrant's partner as well either through the partner's risk behaviors while the migrant is away, such as the partner having additional partners, or via exposure to the return migrant.Using data from the 2010-11 Zimbabwe Demographic and Health Survey, weighted generalized linear regression models were used to investigate the associations between short-term mobility and partnership concurrency at the individual and partnership levels.At the individual level, we find strong evidence of an association between short-term mobility and concurrency. Men who traveled were more likely to have concurrent partnerships compared to men who did not travel and the relationship was non-linear: each trip was associated with a 2% higher probability of concurrency, with a diminishing risk at 60 trips (p<0.001. At the partnership level, short-term mobility by the male only or both partners was associated with male concurrency. Couples in which the female only traveled exhibited less male concurrency.Short-term mobility has the ability to impact population-level transmission dynamics by facilitating partnership concurrency and thus onward HIV transmission. Short-term migrants may be an important population to target for HIV testing, treatment, or social and behavioral interventions to prevent the spread of HIV.

  3. Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing.

    Directory of Open Access Journals (Sweden)

    Dieter Hoffmann

    Full Text Available Simple and cost-effective approaches for HIV drug-resistance testing are highly desirable for managing increasingly expanding HIV-1 infected populations who initiate antiretroviral therapy (ART, particularly in resource-limited settings. Non-nucleoside reverse trancriptase inhibitor (NNRTI-based regimens with an NRTI backbone containing lamivudine (3TC or emtricitabine (FTC are preferred first ART regimens. Failure with these drug combinations typically involves the selection of NNRTI- and/or 3TC/FTC-resistant viruses. Therefore, the availability of simple assays to measure both types of drug resistance is critical. We have developed a high throughput screening test for assessing enzymatic resistance of the HIV-1 RT in plasma to 3TC/FTC and NNRTIs. The test uses the sensitive "Amp-RT" assay with a newly-developed real-time PCR format to screen biochemically for drug resistance in single reactions containing either 3TC-triphosphate (3TC-TP or nevirapine (NVP. Assay cut-offs were defined based on testing a large panel of subtype B and non-subtype B clinical samples with known genotypic profiles. Enzymatic 3TC resistance correlated well with the presence of M184I/V, and reduced NVP susceptibility was strongly associated with the presence of K103N, Y181C/I, Y188L, and G190A/Q. The sensitivity and specificity for detecting resistance were 97.0% and 96.0% in samples with M184V, and 97.4% and 96.2% for samples with NNRTI mutations, respectively. We further demonstrate the utility of an HIV capture method in plasma by using magnetic beads coated with CD44 antibody that eliminates the need for ultracentifugation. Thus our results support the use of this simple approach for distinguishing WT from NNRTI- or 3TC/FTC-resistant viruses in clinical samples. This enzymatic testing is subtype-independent and can assist in the clinical management of diverse populations particularly in resource-limited settings.

  4. A prophylactic amputation

    Directory of Open Access Journals (Sweden)

    Faria Afsana

    2010-10-01

    Full Text Available A case of amputation of the fourth toe is described in a diabetic patient. The patient had overlapping of third and fourth toes since her childhood and later she developed soft lipomas over the fourth toe and lateral aspect of the dorsum of the foot. The lipomas were excised without relief of pain. Subsequently, the fourth toe was disarticulated with relief of pain and healing of ulcers. The role of prophylactic amputations in such cases is described. Ibrahim Med. Coll. J. 2010; 4(2: 87-89

  5. mCME project V.2.0: randomised controlled trial of a revised SMS-based continuing medical education intervention among HIV clinicians in Vietnam.

    Science.gov (United States)

    Gill, Christopher J; Le, Ngoc Bao; Halim, Nafisa; Chi, Cao Thi Hue; Nguyen, Viet Ha; Bonawitz, Rachael; Hoang, Pham Vu; Nguyen, Hoang Long; Huong, Phan Thi Thu; Larson Williams, Anna; Le, Ngoc Anh; Sabin, Lora

    2018-01-01

    Continuing medical education (CME) is indispensable, but costs are a barrier. We tested the effectiveness of a novel mHealth intervention (mCME V.2.0) promoting CME among Vietnamese HIV clinicians. We enrolled HIV clinicians from three provinces near Hanoi. The 6-month intervention consisted of (1) daily short message service multiple-choice quiz questions, (2) daily linked readings, (3) links to online CME courses and (4) feedback messages describing the performance of the participant relative to the group. Control participants had equal access to the online CME courses. Our primary endpoint was utilisation of the online CME courses; secondary endpoints were self-study behaviour, performance on a standardised medical exam and job satisfaction. From 121 total HIV clinicians in the three provinces, 106 (87.6%) enrolled, and 48/53 intervention (90%) and 47/53 control (89%) participants completed the endline evaluations. Compared with controls, intervention participants were more likely to use the CME courses (risk ratio (RR) 2.3, 95% CI 1.4 to 3.8, accounting for 83% of course use (P<0.001)). Intervention participants increased self-study behaviours over controls in terms of use of medical textbooks (P<0.01), consulting with colleagues (P<0.01), searching on the internet (P<0.001), using specialist websites (P=0.02), consulting the Vietnam HIV/AIDS treatment guidelines (P=0.02) and searching the scientific literature (P=0.09). Intervention participants outperformed controls on the exam (+23% vs +12% score gains, P=0.05) and had higher job satisfaction. The mCME V.2.0 intervention improved self-study behaviour, medical knowledge and job satisfaction. This approach has potential for expansion in Vietnam and similar settings. NCT02381743.

  6. CERN Technical Training: available places in forthcoming courses

    CERN Multimedia

    HR Department

    2009-01-01

    The following course sessions are scheduled in the framework of the 2009 CERN Technical Training Programme and places are still available. You can find the full updated Technical Training course programme in our web catalogue (http://cta.cern.ch/cta2/f?p=110:9). OFFICE SOFTWARE Outlook 2007 (Short Course 1) – E-mail\t(Bilingual)\t25.05\t3 hours Outlook 2007 (Short Course II) – Calendar, Tasks and Notes (Bilingual)\t25.05\t3 hours Word 2007 (Short Course III) - Working with long documents: Styles and tables of content (Bilingual)\t28.05\t3 hours Excel 2007 (Short Course I) –HowTo…Work with formulae (Bilingual)\t11.06\t0.5 jour/day Excel 2007 (Short Course II) – HowTo…Format your worksheet for printing\t(Bilingual)\t11.06\t0.5 jour/day Excel 2007 (Short Course III) – HowTo…Pivot Tables\t(Bilingual)\t12.06\t0.5 jour/day Excel 2007 (Short Course IV) – HowTo…Link cells, worksheets and workbook\t(Bilingual)\t12.06\t0.5 jour/day Word 2007 – Level 1: ECDL\t(Français)\t15-...

  7. Prophylaxis and follow-up after possible exposure to HIV, hepatitis B virus, and hepatitis C virus outside hospital: evaluation of policy 2000-3

    NARCIS (Netherlands)

    Sonder, Gerard J. B.; Regez, Rosa M.; Brinkman, Kees; Prins, Jan M.; Mulder, Jan-Willem; Spaargaren, Joke; Coutinho, Roel A.; van den Hoek, Anneke

    2005-01-01

    Problem Prophylactic treatment and follow-up after exposure to HIV, hepatitis B, and hepatitis C outside hospital needs to be improved. Background and setting Until January 2000, people in Amsterdam Could report exposure outside hospital to either a hospital or the municipal health service. If they

  8. The Significance of Sexuality and Intimacy in the Lives of Older African Americans With HIV/AIDS

    Science.gov (United States)

    Nevedal, Andrea; Sankar, Andrea

    2016-01-01

    Purpose of the Study: Aging and HIV/AIDS research focuses primarily on standardized clinical, social, and behavioral measures, leaving unanswered questions about how this chronic and stigmatizing condition affects life course expectations and the meaning of aging with the disease. Utilizing Gaylene Becker’s (1997) life course disruption theory, we explored older African Americans’ experiences of living with HIV/AIDS. Design and Methods: A purposive sample (N = 43) of seropositive African Americans aged 50 and older was selected from a parent study. Thirteen participants completed one semi-structured in-depth interview on life course expectations and experiences of living with HIV/AIDS. Interview transcripts were analyzed using standard qualitative coding and thematic analysis. Results: Responding to broad, open-ended questions about the impact of HIV on life course expectations, participants emphasized how HIV limited their ability to experience sexuality and intimacy. Two major themes emerged, damaged sexuality and constrained intimacy. Implications: Older African Americans’ discussions of living with HIV focused on the importance of and the challenges to sexuality and intimacy. Researchers and clinicians should be attentive to significant and ongoing HIV-related challenges to sexuality and intimacy facing older African Americans living with HIV/AIDS. PMID:26035889

  9. Effect of exposure to clinic-based health education interventions on ...

    African Journals Online (AJOL)

    HIV and AIDS incidence among infants in South Africa is on the increase.The uptake of ..... error. 1. Behavioural belief. –.108 .051. –.119. –2.097 .037*. Normative belief .046 .069 .037 ..... explained by the wide social marketing nevirapine in.

  10. Disease severity, self-reported experience of workplace discrimination and employment loss during the course of chronic HIV disease: differences according to gender and education.

    Science.gov (United States)

    Dray-Spira, R; Gueguen, A; Lert, F

    2008-02-01

    Evidence for the existence of a harmful effect of chronic disease on employment status has been provided. Although this effect of chronic illness on employment has been reported to be higher among the groups with the lowest position on the labour market, the mechanisms of such inequalities are poorly understood. The present study aimed at investigating social inequalities in the chances of maintaining employment during the course of HIV infection and at examining the correlates of such inequalities. The authors used data from a national representative sample of people living with HIV in France (ANRS-EN12-VESPA survey). Retrospective information on social trajectory and disease characteristics from the time of HIV diagnosis was available. The risk of employment loss associated with indicators of disease severity and HIV-related workplace discrimination was computed over time since HIV diagnosis according to sociodemographic and occupational factors, using Cox proportional hazards models. Among the 478 working-age participants diagnosed as being HIV-infected in the era of multitherapies and employed at the time of HIV diagnosis, 149 experienced employment loss. After adjusting for sociodemographic and occupational factors, disease severity and self-reported HIV-related discrimination at work were significantly associated with the risk of employment loss in a socially-differentiated manner: advancement in HIV disease was associated with an increased risk of employment loss among women (HR 4.45, 95% CI 2.10 to 9.43) but not among men; self-reported experience of HIV-related discrimination at work was associated with an increased risk of employment loss among individuals with a primary/secondary educational level (HR 8.85, 95% CI 3.68 to 21.30) but not among those more educated. Chronic HIV disease affects the chances of maintaining employment in a socially-differentiated manner, resulting in increasing inequalities regarding workforce participation. Disease severity

  11. Influence of common mucosal co-factors on HIV infection in the female genital tract.

    Science.gov (United States)

    Ferreira, Victor H; Kafka, Jessica K; Kaushic, Charu

    2014-06-01

    Women constitute almost half of HIV-infected population globally, and the female genital tract (FGT) accounts for approximately 40% of all new HIV infections worldwide. The FGT is composed of upper and lower parts, distinct in their morphological and functional characteristics. Co-factors in the genital microenvironment, such as presence of hormones, semen, and other sexually transmitted infections, can facilitate or deter HIV infection and play a critical role in determining susceptibility to HIV. In this review, we examine some of these co-factors and their potential influence. Presence of physical and chemical barriers such as epithelial tight junctions, mucus, and anti-microbial peptides can actively block and inhibit viral replication, presenting a significant deterrent to HIV. Upon exposure, HIV and other pathogens first encounter the genital epithelium: cells that express a wide repertoire of pattern recognition receptors that can recognize and directly initiate innate immune responses. These and other interactions in the genital tract can lead to direct and indirect inflammation and enhance the number of local target cells, immune activation, and microbial translocation, all of which promote HIV infection and replication. Better understanding of the dynamics of HIV transmission in the female genital tract would be invaluable for improving the design of prophylactic strategies against HIV. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Human Paraoxonase-1 Activity Is Related to the Number of CD4+ T-Cells and Is Restored by Antiretroviral Therapy in HIV-1-Infected Individuals

    Directory of Open Access Journals (Sweden)

    Luciana Morganti Ferreira Maselli

    2014-01-01

    Full Text Available Background. Paraoxonase-1 (PON1 activity is suggested to be altered in individuals infected with human immunodeficiency virus type-1 (HIV-1. We investigated PON1 activity in individuals receiving different regimens of highly active antiretroviral therapy (HAART. Methods. PON1 activity was evaluated in 91 HIV-1 seronegative and 624 HIV-1 infected individuals (115 were not undergoing therapy (ART-naïve, and 509 were receiving HAART. HIV-1 infected individuals were treated with the following: efavirenz (EFV; n=195 or nevirapine (NVP; n=95 or lopinavir/ritonavir (LOP/r; n=219. Serum levels of total cholesterol (TC, HDL, and low-density lipoprotein (LDL fractions and the atherogenic indices (AI, TC : HDL, and LDL : HDL ratios were determined. Results. PON1 activity (U/L was lower in the ART-naïve group compared with the other groups. PON1 activity correlated with CD4+ T-cell number of ART-naïve group (r=0,121; P=0,014. The LOP/r group showed a reduction in HDL and an increase in AI (TC : HDL ratio in comparison with other groups. Conclusion. PON1 activity was reduced in untreated individuals, but not in individuals receiving HAART. PON1 activity correlated with the number of CD4+ T-cells. The findings suggest that the activity of PON1 is associated with the immune status of HIV-1 infected individuals.

  13. Using Short Videos in an Introductory Programming Course

    DEFF Research Database (Denmark)

    Nørmark, Kurt

    2014-01-01

    Video resources are gradually being introduced in a first year programming course. The course is about imperative programming in C. After each of the first two years with video lectures the students have been asked about their assessments and opinions. The main parts of the paper are based on evi...... experience we also carry out a discussion of future plans for using video resources in the course....

  14. SHORT COMMUNICATION High prevalence of Plasmodium ...

    African Journals Online (AJOL)

    Dell

    Volume 20, Number 1, January 2018. 1. SHORT COMMUNICATION ... This study was designed to establish the prevalence of Plasmodium falciparum malaria among HIV infected populations. ... The prevalence of P. falciparum was high among HIV seropositive individuals in the Lake Victoria Zone, which calls for additional ...

  15. Short Course Introduction to Quantitative Mineral Resource Assessments

    Science.gov (United States)

    Singer, Donald A.

    2007-01-01

    This is an abbreviated text supplementing the content of three sets of slides used in a short course that has been presented by the author at several workshops. The slides should be viewed in the order of (1) Introduction and models, (2) Delineation and estimation, and (3) Combining estimates and summary. References cited in the slides are listed at the end of this text. The purpose of the three-part form of mineral resource assessments discussed in the accompanying slides is to make unbiased quantitative assessments in a format needed in decision-support systems so that consequences of alternative courses of action can be examined. The three-part form of mineral resource assessments was developed to assist policy makers evaluate the consequences of alternative courses of action with respect to land use and mineral-resource development. The audience for three-part assessments is a governmental or industrial policy maker, a manager of exploration, a planner of regional development, or similar decision-maker. Some of the tools and models presented here will be useful for selection of exploration sites, but that is a side benefit, not the goal. To provide unbiased information, we recommend the three-part form of mineral resource assessments where general locations of undiscovered deposits are delineated from a deposit type's geologic setting, frequency distributions of tonnages and grades of well-explored deposits serve as models of grades and tonnages of undiscovered deposits, and number of undiscovered deposits are estimated probabilistically by type. The internally consistent descriptive, grade and tonnage, deposit density, and economic models used in the design of the three-part form of assessments reduce the chances of biased estimates of the undiscovered resources. What and why quantitative resource assessments: The kind of assessment recommended here is founded in decision analysis in order to provide a framework for making decisions concerning mineral

  16. Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals after First-Line Antiretroviral Therapy Failure in South Africa.

    Science.gov (United States)

    Penrose, Kerri J; Wallis, Carole L; Brumme, Chanson J; Hamanishi, Kristen A; Gordon, Kelley C; Viana, Raquel V; Harrigan, P Richard; Mellors, John W; Parikh, Urvi M

    2017-02-01

    A vaginal ring containing dapivirine (DPV) has shown moderate protective efficacy against HIV-1 acquisition, but the activity of DPV against efavirenz (EFV)- and nevirapine (NVP)-resistant viruses that could be transmitted is not well defined. We investigated DPV cross-resistance of subtype C HIV-1 from individuals on failing NVP- or EFV-containing antiretroviral therapy (ART) in South Africa. Plasma samples were obtained from individuals with >10,000 copies of HIV RNA/ml and with HIV-1 containing at least one non-nucleoside reverse transcriptase (NNRTI) mutation. Susceptibility to NVP, EFV, and DPV in TZM-bl cells was determined for recombinant HIV-1 LAI containing bulk-amplified, plasma-derived, full-length reverse transcriptase sequences. Fold change (FC) values were calculated compared with a composite 50% inhibitory concentration (IC 50 ) from 12 recombinant subtype C HIV-1 LAI plasma-derived viruses from treatment-naive individuals in South Africa. A total of 25/100 (25%) samples showed >500-FCs to DPV compared to treatment-naive samples with IC 50 s exceeding the maximum DPV concentration tested (132 ng/ml). A total of 66/100 (66%) samples displayed 3- to 306-FCs, with a median IC 50 of 17.6 ng/ml. Only 9/100 (9%) samples were susceptible to DPV (FC 500-fold resistance to DPV compared to samples with a ≤500-fold resistance. A total of 91% of samples with NNRTI-resistant HIV-1 from individuals on failing first-line ART in South Africa exhibited ≥3-fold cross-resistance to DPV. This level of resistance exceeds expected plasma concentrations, but very high genital tract DPV concentrations from DPV ring use could block viral replication. It is critically important to assess the frequency of transmitted and selected DPV resistance in individuals using the DPV ring. Copyright © 2017 American Society for Microbiology.

  17. CERN Technical Training: available Places in forthcoming Courses

    CERN Multimedia

    HR Department

    2009-01-01

    The following course sessions are scheduled in the framework of the 2009 CERN Technical Training Programme and places are still available. You can find the full updated Technical Training course programme in our web catalogue (http://cta.cern.ch/cta2/f?p=110:9). OFFICE SOFTWARE Outlook 2007 (Short Course 1) – E-mail\t(Bilingual)\t25.05\t3 hours Outlook 2007 (Short Course II) – Calendar, Tasks and Notes (Bilingual)\t25.05\t3 hours Word 2007 (Short Course III) - Working with long documents: Styles and tables of content\t(Bilingual)\t28.05\t3 hours Indico – Meeting Organization\t(English)\t05.06\t2 hours Indico – Conference Organization\t(Français)\t05.06\t3 hours Excel 2007 (Short Course I) –HowTo…Work with formulae (Bilingual)\t11.06\t0.5 jour/day Excel 2007 (Short Course II) – HowTo…Format your worksheet for printing\t(Bilingual)\t11.06\t0.5 jour/day Excel 2007 (Short Course III) – HowTo…Pivot Tables\t(Bilingual)\t12.06\t0.5 jour/day Excel 2007 (Short Course IV) – HowTo…Link cells, worksheets and workb...

  18. Impact on practice of a British Association for Sexual Health and HIV Sexually Transmitted Infections Foundation (STIF) course: an audit of the first four years in Ireland.

    Science.gov (United States)

    Calamai, A; Howard, R; Kelly, R; Lambert, J

    2013-02-01

    In order to investigate the overall impact of the British Association for Sexual Health and HIV (BASHH) Sexually Transmitted Infections Foundation (STIF) course taught in Ireland since 2007, attendees were sent two questionnaires to investigate the overall impact of the course, its effect on clinical practice and the need for further education. Response rate was 19.4%. The majority found the course beneficial and that it did cover their practice needs (96.4%), with 83.6% saying that their confidence and technique in sexual history taking had improved. There was a 3.7% increase in the provision of HIV testing from precourse levels, although only 80% did so routinely; a 12.7% increase in syphilis testing; a 5.4% increase in testing for Chlamydia and a 12.7% increase for gonorrhoea. Some confusion seems to persist in relation to sexually transmitted infection (STI) risk factors. The second questionnaire tested STI knowledge. Most respondents scored well (average 81% correct answers); however, respondents who attended four years previously scored, on average, 7% worse than the others, suggesting the need for a periodic update in the area of STI education.

  19. Decrease of vitamin D concentration in patients with HIV infection on a non nucleoside reverse transcriptase inhibitor-containing regimen

    Directory of Open Access Journals (Sweden)

    Colebunders Robert

    2010-11-01

    Full Text Available Abstract Background Vitamin D is an important determinant of bone health and also plays a major role in the regulation of the immune system. Interestingly, vitamin D status before the start of highly active antiretroviral therapy (HAART has been recently associated with HIV disease progression and overall mortality in HIV-positive pregnant women. We prospectively studied vitamin D status in HIV individuals on HAART in Belgium. We selected samples from HIV-positive adults starting HAART with a pre-HAART CD4 T-cell count >100 cells/mm3 followed up for at least 12 months without a treatment change. We compared 25-hydroxyvitamin D plasma [25-(OHD] concentration in paired samples before and after 12 months of HAART. 25-(OHD levels are presented using two different cut-offs: Results Vitamin D deficiency was common before HAART, the frequency of plasma 25-(OHD concentrations below 20 ng/ml and 30 below ng/ml was 43.7% and 70.1% respectively. After 12 months on HAART, the frequency increased to 47.1% and 81.6%. HAART for 12 months was associated with a significant decrease of plasma 25-(OHD concentration (p = 0.001. Decreasing plasma 25-(OHD concentration on HAART was associated in the multivariate model with NNRTI-based regimen (p = 0.001 and lower body weight (p = 0.008. Plasma 25-(OHD concentrations decreased significantly in both nevirapine and efavirenz-containing regimens but not in PI-treated patients. Conclusions Vitamin D deficiency is frequent in HIV-positive individuals and NNRTI therapy further decreases 25-(OHD concentrations. Consequently, vitamin D status need to be checked regularly in all HIV-infected patients and vitamin D supplementation should be given when needed.

  20. Effect of prophylactic CPAP in very low birth weight infants in South America.

    Science.gov (United States)

    Zubizarreta, J R; Lorch, S A; Marshall, G; D'Apremont, I; Tapia, J L

    2016-08-01

    The objective of this study was to examine the effect of prophylactic continuous positive airway pressure (CPAP) on infants born in 25 South American neonatal intensive care units affiliated with the Neocosur Neonatal Network using novel multivariate matching methods. A prospective cohort was constructed of infants with a birth weight 500 to 1500 g born between 2005 and 2011 who clinically were eligible for prophylactic CPAP. Patients who received prophylactic CPAP were matched to those who did not on 23 clinical and sociodemographic variables (N=1268). Outcomes were analyzed using the McNemar's test. Infants not receiving prophylactic CPAP had higher mortality rates (odds ratio (OR)=1.69, 95% confidence interval (CI) 1.17, 2.46), need for any mechanical ventilation (OR=1.68, 95% CI 1.33, 2.14) and death or bronchopulmonary dysplasia (BPD) (OR=1.47, 95% CI 1.09, 1.98). The benefit of prophylactic CPAP varied by birth weight and gender. The implementation of this process was associated with a significant improvement in survival and survival free of BPD.

  1. Is HIV-2- induced AIDS different from HIV-1-associated AIDS? Data from a West African clinic

    NARCIS (Netherlands)

    Martinez-Steele, Euridice; Awasana, Akum Aveika; Corrah, Tumani; Sabally, Saihou; van der Sande, Marianne; Jaye, Assan; Togun, Toyin; Sarge-Njie, Ramu; McConkey, Samuel J.; Whittle, Hilton; Schim van der Loeff, Maarten F.

    2007-01-01

    Although AIDS is less frequent following HIV-2 than HIV-1 infection, it is unclear whether the clinical picture and clinical course of AIDS are similar in the two infections. To compare the pattern of AIDS-defining events, CD4 cell count at the time of AIDS diagnosis, survival from time of AIDS, and

  2. Factors Associated With the Prophylactic Prescription of a Bowel Regimen to Prevent Opioid-Induced Constipation.

    Science.gov (United States)

    Chen, Nancy Y; Nguyen, Eugene; Schrager, Sheree M; Russell, Christopher J

    2016-11-01

    Identify factors associated with the prophylactic prescription of a bowel regimen with an inpatient opioid prescription. This was a retrospective cohort study from June 1, 2013, to October 31, 2014 of pediatric inpatients prescribed an oral or intravenous opioid on the general medical/surgical floors. We identified patients with or without a prophylactic prescription of a bowel regimen. We obtained patient demographics, prescriber training level and service and used multivariate logistic regression to analyze the factors associated with prophylactic bowel regimen and opioid prescription. Of the 6682 encounters that met study criteria, only 966 (14.5%) encounters had prophylactic prescriptions. Patient factors associated with prophylactic prescription include increasing age (per year; odds ratio [OR] = 1.06, 95% confidence interval [CI] 1.05-1.07) and sickle cell diagnosis (OR = 3.19, 95% CI 2.08-4.91). Medication factors associated with prophylactic prescription include a scheduled opioid prescription (OR = 1.75, 95% CI 1.46-2.1) and a prescription for oxycodone (OR = 3.59, 95% CI 2.57-5.00) or morphine (OR = 1.84, 95% CI 1.39-2.44), compared with acetaminophen-hydrocodone. Compared with medical providers, surgeons were less likely (OR = 0.43, 95% CI 0.35-0.53) and pain service providers were more likely to prescribe a prophylactic bowel regimen (OR = 4.12, 95% CI 3.13-5.43). More than 85% of inpatient opioid prescriptions did not receive a prophylactic bowel regimen. Future research should examine factors (eg, clinical decision support tools) to increase prophylactic prescription of bowel regimens with opioids for populations found to have lower rates. Copyright © 2016 by the American Academy of Pediatrics.

  3. What are the learning outcomes of a short postgraduate training course in dermatology for primary care doctors?

    Science.gov (United States)

    2011-01-01

    Background There are increasing expectations on primary care doctors to shoulder a bigger share of care for patients with common dermatological problems in the community. This study examined the learning outcomes of a short postgraduate course in dermatology for primary care doctors. Methods A self-reported questionnaire developed by the research team was sent to the Course graduates. A retrospective design was adopted to compare their clinical practice characteristics before and after the Course. Differences in the ratings were analysed using the nonparametric Wilcoxon signed rank test to evaluate the effectiveness of the Course in various aspects. Results Sixty-nine graduates replied with a response rate of 42.9% (69/161). Most were confident of diagnosing (91.2%) and managing (88.4%) common dermatological problems after the Course, compared to 61.8% and 58.0% respectively before the Course. Most had also modified their approach and increased their attention to patients with dermatological problems. The number of patients with dermatological problems seen by the graduates per day showed significant increase after the Course, while the average percentage of referrals to dermatologists dropped from 31.9% to 23.5%. The proportion of graduates interested in following up patients with chronic dermatological problems increased from 60.3% to 77.9%. Conclusions Graduates of the Course reported improved confidence, attitudes and skills in treating common dermatological problems. They also reported to handle more patients with common dermatological problems in their practice and refer fewer patients. PMID:21575191

  4. Immune activation and HIV-specific T cell responses are modulated by a cyclooxygenase-2 inhibitor in untreated HIV-infected individuals: An exploratory clinical trial.

    Directory of Open Access Journals (Sweden)

    Christian Prebensen

    Full Text Available Pathologically elevated immune activation and inflammation contribute to HIV disease progression and immunodeficiency, potentially mediated by elevated levels of prostaglandin E2, which suppress HIV-specific T cell responses. We have previously shown that a high dose of the cyclooxygenase-2 inhibitor celecoxib can reduce HIV-associated immune activation and improve IgG responses to T cell-dependent vaccines. In this follow-up study, we included 56 HIV-infected adults, 28 antiretroviral therapy (ART-naïve and 28 on ART with undetectable plasma viremia but CD4 counts below 500 cells/μL. Patients in each of the two study groups were randomized to receive 90 mg qd of the cyclooxygenase-2 inhibitor etoricoxib for six months, two weeks or to a control arm, respectively. T cell activation status, HIV Gag-specific T cell responses and plasma inflammatory markers, tryptophan metabolism and thrombin generation were analyzed at baseline and after four months. In addition, patients received tetanus toxoid, conjugated pneumococcal and seasonal influenza vaccines, to which IgG responses were determined after four weeks. In ART-naïve patients, etoricoxib reduced the density of the activation marker CD38 in multiple CD8+ T cell subsets, improved Gag-specific T cell responses, and reduced in vitro plasma thrombin generation, while no effects were seen on plasma markers of inflammation or tryptophan metabolism. No significant immunological effects of etoricoxib were observed in ART-treated patients. Patients receiving long-term etoricoxib treatment had poorer tetanus toxoid and conjugated pneumococcal vaccine responses than those receiving short-course etoricoxib. Cyclooxygenase-2 inhibitors may attenuate harmful immune activation in HIV-infected patients without access to ART.

  5. The Significance of Sexuality and Intimacy in the Lives of Older African Americans With HIV/AIDS.

    Science.gov (United States)

    Nevedal, Andrea; Sankar, Andrea

    2016-08-01

    Aging and HIV/AIDS research focuses primarily on standardized clinical, social, and behavioral measures, leaving unanswered questions about how this chronic and stigmatizing condition affects life course expectations and the meaning of aging with the disease. Utilizing Gaylene Becker's (1997) life course disruption theory, we explored older African Americans' experiences of living with HIV/AIDS. A purposive sample (N = 43) of seropositive African Americans aged 50 and older was selected from a parent study. Thirteen participants completed one semi-structured in-depth interview on life course expectations and experiences of living with HIV/AIDS. Interview transcripts were analyzed using standard qualitative coding and thematic analysis. Responding to broad, open-ended questions about the impact of HIV on life course expectations, participants emphasized how HIV limited their ability to experience sexuality and intimacy. Two major themes emerged, damaged sexuality and constrained intimacy. Older African Americans' discussions of living with HIV focused on the importance of and the challenges to sexuality and intimacy. Researchers and clinicians should be attentive to significant and ongoing HIV-related challenges to sexuality and intimacy facing older African Americans living with HIV/AIDS. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Impact of glutathione transferases genes polymorphisms in nevirapine adverse reactions: a possible role for GSTM1 in SJS/TEN susceptibility.

    Science.gov (United States)

    Ciccacci, Cinzia; Latini, Andrea; Politi, Cristina; Mancinelli, Sandro; Marazzi, Maria C; Novelli, Giuseppe; Palombi, Leonardo; Borgiani, Paola

    2017-10-01

    Nevirapine (NVP) is used in developing countries as first-line treatment of HIV infection. Unfortunately, its use is associated with common serious adverse drug reactions, such as liver toxicity and the most severe and rare Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). GSTT1 and GSTM1 genes code for enzymes involved in the metabolism of a wide range of drugs. We hypothesized that this gene variability could be implicated in NVP adverse reactions. We analyzed the GSTM1 and GSTT1 null genotypes by multiplex PCR in a population of 181 patients from Mozambique, treated with NVP. A case/control association study was performed. We also counted the number of risk alleles in SJS/TEN patients and in controls, including the GSTM1 null genotype and four previously identified risk alleles in CYP2B6, HCP5, and TRAF3IP2 genes. Among patients, 27 had developed SJS/TEN and 76 had developed hepatotoxicity during the treatment. The GSTM1 null genotype was more frequent in the cases with SJS/TEN than in the controls (OR = 2.94, P = 0.027). This association is also observed when other risk factors are taken into account, by a multivariate analysis (P = 0.024 and OR = 3.58). The risk allele counting analysis revealed a significantly higher risk for SJS/TEN in patients carrying three or four risk alleles. Moreover, all subjects with five or six risk alleles developed SJS/TEN, while subjects without any risk alleles were present only in the control group. We observed an association between GSTM1 and SJS/TEN susceptibility. Moreover, GSTM1 contributes to the definition of a genetic risk profile for SJS/TEN susceptibility.

  7. Environmental Shortcourse Final report [Joint US-EC Short Course on Environmental Biotechnology: Microbial Catalysts for the Environment

    Energy Technology Data Exchange (ETDEWEB)

    Zylstra, Gerben; van der Meer, Jan Roelof

    2013-03-05

    The Joint US-EC Short Course on Environmental Biotechnology is designed for several purposes. One of the central tenets is to bring together young scientists (at the late Ph.D. or early postdoctoral stages of their careers) in a forum that will set the groundwork for future overseas collaborative interactions. The course is also designed to give the scientists hands-on experience in modern, up-to-date biotechnological methods for the analysis of microbes and their activities pertinent to the remediation of pollutants in the environment. The 2011 course covered multiple theoretical and practical topics in environmental biotechnology. The practical part was centered around a full concise experiment to demonstrate the possibility for targeted remediation of contaminated soil. Experiments included chemical, microbiological, and molecular analyses of sediments and/or waters, contaminant bioavailability assessment, seeded bioremediation, gene probing, PCR amplification, microbial community analysis based on 16S rRNA gene diversity, and microarray analyses. Each of these topics is explained in detail. The practical part of the course was complemented with two lectures per day, given by distinguished scientists from the US and from Europe, covering a research area related to what the students are doing in the course.

  8. Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development.

    Science.gov (United States)

    Schiffer, Joshua T; Gottlieb, Sami L

    2017-09-25

    Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa. These cells are targets for HIV entry and replication. Prophylactic HSV-2 vaccines (to prevent infection) and therapeutic vaccines (to modify or treat existing infections) are currently under development. By preventing or modifying infection, an effective HSV-2 vaccine could limit HSV-associated genital mucosal inflammation and thus HIV risk. However, a vaccine might have competing effects on HIV risk depending on its mechanism of action and cell populations generated in the genital mucosa. In this article, we review biologic interactions between HSV-2 and HIV-1, consider HSV-2 vaccine development in the context of HIV risk, and discuss implications and research needs for future HSV vaccine development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Usage of prophylactic radiologically inserted gastrostomy in head and neck cancer patients

    International Nuclear Information System (INIS)

    Mallinson, P.I.; Tun, J. Kyaw; Byass, O.R.; Cast, J.E.I.

    2012-01-01

    Aim: To assess outcomes and usage rate of prophylactic radiologically inserted gastrostomy (RIG) in head and neck cancer (HNC) patients. Materials and methods: Outcome data of all HNC patients who underwent prophylactic RIG over a 22-month period (November 2007 to September 2009) in a tertiary referral centre were collected retrospectively. Thirty-day mortality, major and minor complication rates, and subsequent usage of the RIG were analysed. Results: Fifty-one HNC patients underwent prophylactic RIG. Three minor and no major immediate complications were identified. Sixteen minor and three major complications at 30-days were identified. Three (5.9%) major complications were identified. There was one death due to disease progression and not RIG insertion. The RIG was not used in 17.7% of patients post-procedure. Conclusion: Prophylactic RIG in HNC patients has a comparable mortality rate to RIG insertion in HNC patients with mixed indications. However, the number of cases where the gastrostomy is not used raises important concerns and warrants further investigation.

  10. Effectiveness of a short-course in improving knowledge and skills on evidence-based practice

    Directory of Open Access Journals (Sweden)

    Jiménez-Villa Josep

    2011-06-01

    Full Text Available Abstract Background To assess the effectiveness (change in knowledge and skills measured by the Fresno test of a short course in Evidence Based Practice (EBP carried out in a group of family medicine residents Methods Before-after study. Participants' were 152 Family Medicine residents in their second year of the training programme. Settings were Primary Care Teaching Units in Catalonia. Intervention was comprised of a four half-day training course designed to develop the knowledge and skills required to practice evidence-based care. The main outcome measure was change in EBP knowledge and skills, measured using the Spanish version of the Fresno test (score range, 0-212 Results The mean difference between pre-test and post-test was 47.7, a statistically significant result with 95% CI of 42.8-52.5 (p Conclusions The study provides evidence for responsiveness to changes in knowledge and skills in EBP after an educational intervention.

  11. Lipid profile of HIV-infected patients in relation to antiretroviral therapy: a review.

    Science.gov (United States)

    Souza, Suelen Jorge; Luzia, Liania Alves; Santos, Sigrid Sousa; Rondó, Patrícia Helen Carvalho

    2013-01-01

    This study reviewed the lipid profile of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in relation to use of antiretroviral therapy (ART), and its different classes of drugs. A total of 190 articles published in peer-reviewed journals were retrieved from PubMed and LILACS databases; 88 of them met the selection criteria and were included in the review. Patients with HIV/AIDS without ART presented an increase of triglycerides and decreases of total cholesterol, low density lipoprotein (LDL-c), and high density lipoprotein (HDL-c) levels. Distinct ART regimens appear to promote different alterations in lipid metabolism. Protease inhibitors, particularly indinavir and lopinavir, were commonly associated with hypercholesterolemia, high LDL-c, low HDL-c, and hypertriglyceridemia. The protease inhibitor atazanavir is apparently associated with a more advantageous lipid profile. Some nucleoside reverse-transcriptase inhibitors (didanosine, stavudine, and zidovudine) induced lipoatrophy and hypertriglyceridemia, whereas abacavir increased the risk of cardiovascular diseases even in the absence of apparent lipid disorders, and tenofovir resulted in lower levels of cholesterol and triglycerides. Although non-nucleoside reverse-transcriptase inhibitors predisposed to hypertriglyceridemia and hypercholesterolemia, nevirapine was particularly associated with high HDL-c levels, a protective factor against cardiovascular diseases. Therefore, the infection itself, different classes of drugs, and some drugs from the same class of ART appear to exert distinct alterations in lipid metabolism. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  12. Standard (60 Gy) or Short-Course (40 Gy) Irradiation Plus Concomitant and Adjuvant Temozolomide for Elderly Patients With Glioblastoma: A Propensity-Matched Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it [Radiation Oncology Unit, Sant' Andrea Hospital, University Sapienza, Rome (Italy); Scientific Institute for Research, Hospitalization and Health Care (IRCCS) Neuromed, Pozzilli (Italy); Scaringi, Claudia [Radiation Oncology Unit, Sant' Andrea Hospital, University Sapienza, Rome (Italy); Lanzetta, Gaetano [Scientific Institute for Research, Hospitalization and Health Care (IRCCS) Neuromed, Pozzilli (Italy); Terrenato, Irene [Biostatistic Unit, Regina Elena National Cancer Institute, Rome (Italy); Esposito, Vincenzo; Arcella, Antonella [Scientific Institute for Research, Hospitalization and Health Care (IRCCS) Neuromed, Pozzilli (Italy); Pace, Andrea [Neurology Unit, Regina Elena National Cancer Institute, Rome (Italy); Giangaspero, Felice [Scientific Institute for Research, Hospitalization and Health Care (IRCCS) Neuromed, Pozzilli (Italy); Bozzao, Alessandro [Neuroradiology Unit, Sant' Andrea Hospital, University Sapienza, Rome (Italy); Enrici, Riccardo Maurizi [Radiation Oncology Unit, Sant' Andrea Hospital, University Sapienza, Rome (Italy)

    2015-01-01

    Purpose: To evaluate 2 specific radiation schedules, each combined with temozolomide (TMZ), assessing their efficacy and safety in patients aged ≥65 years with newly diagnosed glioblastoma (GBM). Methods and Materials: Patients aged ≥65 years with Karnofsky performance status (KPS) ≥60 who received either standard (60 Gy) or short-course (40 Gy) radiation therapy (RT) with concomitant and adjuvant TMZ between June 2004 and October 2013 were retrospectively analyzed. A propensity score analysis was executed for a balanced comparison of treatment outcomes. Results: A total of 127 patients received standard RT-TMZ, whereas 116 patients underwent short-course RT-TMZ. Median overall survival and progression-free survival times were similar: 12 months and 5.6 months for the standard RT-TMZ group and 12.5 months and 6.7 months for the short-course RT-TMZ group, respectively. Radiation schedule was associated with similar survival outcomes in either unadjusted or adjusted analysis. O{sup 6}-methylguanine-DNA methyltransferase promoter methylation was the most favorable prognostic factor (P=.0001). Standard RT-TMZ therapy was associated with a significant rise in grade 2 and 3 neurologic toxicity (P=.01), lowering of KPS scores during the study (P=.01), and higher posttreatment dosing of corticosteroid (P=.02). Conclusions: In older adults with GBM, survival outcomes of standard and short-course RT-TMZ were similar. An abbreviated course of RT plus TMZ may represent a reasonable therapeutic approach for these patients, without loss of survival benefit and acceptable toxicity.

  13. Long-Term Outcome and Complications Following Prophylactic Laparoscopic-Assisted Gastropexy in Dogs.

    Science.gov (United States)

    Loy Son, Natasha K; Singh, Ameet; Amsellem, Pierre; Kilkenny, Jessica; Brisson, Brigitte A; Oblak, Michelle L; Ogilvie, Adam T

    2016-11-01

    To characterize the short- and long-term outcome (>12 months), complications, and owner satisfaction following prophylactic laparoscopic-assisted gastropexy (LAG) in dogs. Retrospective study. Client-owned dogs (n = 49). Dogs that underwent prophylactic LAG at 2 veterinary academic hospitals were studied. Surgical time, anesthesia time, concurrent intra- and extra-abdominal procedures, and intraoperative and postoperative complications were recorded following review of medical records. Veterinarian and/or owner follow-up was obtained to determine outcome and satisfaction with LAG. Five of 49 dogs (10%) experienced complications related to abdominal access during LAG. Four percent (2/49) of dogs experienced an intraoperative complication. Follow-up information was available for 89% of dogs (44/49). Four dogs died of causes unrelated to LAG or gastric dilatation volvulus (GDV) in the follow-up period. Two dogs experienced major postoperative complications requiring additional veterinary intervention. Thirty percent (13 dogs) experienced a minor postoperative self-limiting wound-related complication. Median follow-up time was 698 days (range, 411-1825). No dogs experienced GDV. One hundred percent of dog owners were satisfied with LAG, would repeat the procedure in a future pet, and would recommend the procedure to a friend or family member. LAG was an effective procedure for prevention of GDV and was associated with high client satisfaction in this cohort of dogs. A moderate rate of postoperative wound complications occurred that were minor and self-limiting in nature. © Copyright 2016 by The American College of Veterinary Surgeons.

  14. Prophylactic Dextrose Gel Does Not Prevent Neonatal Hypoglycemia: A Quasi-Experimental Pilot Study.

    Science.gov (United States)

    Coors, Sarah M; Cousin, Joshua J; Hagan, Joseph L; Kaiser, Jeffrey R

    2018-03-28

    To test the hypothesis that prophylactic dextrose gel administered to newborn infants at risk for hypoglycemia will increase the initial blood glucose concentration after the first feeding and decrease neonatal intensive care unit (NICU) admissions for treatment of asymptomatic neonatal hypoglycemia compared with feedings alone. This quasi-experimental study allocated asymptomatic at-risk newborn infants (late preterm, birth weight 4000 g, and infants of mothers with diabetes) to receive prophylactic dextrose gel (Insta-Glucose; Valeant Pharmaceuticals North America LLC, Bridgewater, New Jersey); other at-risk infants formed the control group. After the initial feeding, the prophylactic group received dextrose gel (0.5 mL/kg) rubbed into the buccal mucosa. The blood glucose concentration was checked 30 minutes later. Initial glucose concentrations and rate of NICU admissions were compared between the prophylactic group and controls using bivariate analyses. A multivariable linear regression compared first glucose concentrations between groups, adjusting for at-risk categories and age at first glucose concentration. There were 236 subjects (72 prophylactic, 164 controls). The first glucose concentration was not different between the prophylactic and control groups in bivariate analysis (52.1 ± 17.1 vs 50.5 ± 15.3 mg/dL, P = .69) and after adjusting for covariates (P  = .18). Rates of NICU admission for treatment of transient neonatal hypoglycemia were 9.7% and 14.6%, respectively (P = .40). Prophylactic dextrose gel did not reduce transient neonatal hypoglycemia or NICU admissions for hypoglycemia. The carbohydrate concentration of Insta-Glucose (77%) may have caused a hyperinsulinemic response, or alternatively, exogenous enteral dextrose influences glucose homeostasis minimally during the first few hours when counter-regulatory mechanisms are especially active. ClinicalTrials.gov: NCT02523222. Copyright © 2018 Elsevier Inc. All

  15. The imaging of HIV-related brain disease | Hoare | Southern African ...

    African Journals Online (AJOL)

    2 In addition, there is growing recognition that many HIV-infected individuals will develop neuropsychiatric disorders relatively early in the course of HIV ... the neurotoxic effects of HIV result in damage to white matter tracts in the brain.6 Once damage is established and related cognitive disorders ensue, the ability of HAART ...

  16. [Prophylactic and therapeutic vaccines against human papilloma virus].

    Science.gov (United States)

    Albers, A E; Hoffmann, T K; Klussmann, J P; Kaufmann, A M

    2010-08-01

    Infection with human papilloma virus (HPV) has been identified as the cause of recurrent papillomatosis and of a subgroup of squamous cell carcinomas of the head and neck. A change in prevalence of these lesions, especially for oropharyngeal carcinoma, can be expected as a consequence of the introduction of prophylactic HPV vaccines for young women, targeting the most frequent high- and low-risk HPV subtypes. Vaccination for the major low-risk HPV types has proven to be highly effective against genital warts and activity against papillomatosis can be expected. The possibilities of prophylactic HPV vaccination as well as new developments and the rationale for therapeutic vaccines are discussed on the basis of the current literature.

  17. Efficacy of postoperative prophylactic antibiotics in reducing permanent pacemaker infections.

    Science.gov (United States)

    Lee, Wen-Huang; Huang, Ting-Chun; Lin, Li-Jen; Lee, Po-Tseng; Lin, Chih-Chan; Lee, Cheng-Han; Chao, Ting-Hsing; Li, Yi-Heng; Chen, Ju-Yi

    2017-08-01

    Despite limited evidence, postoperative prophylactic antibiotics are often used in the setting of permanent pacemaker implantation or replacement. The aim of this study is to investigate the efficacy of postoperative antibiotics. Postoperative prophylactic antibiotics may be not clinically useful. We recruited 367 consecutive patients undergoing permanent pacemaker implantation or generator replacement at a tertiary referral center. Baseline demographics, clinical characteristics, and procedure information were collected, and all patients received preoperative prophylactic antibiotics. Postoperative prophylactic antibiotics were administered at the discretion of the treating physician, and all patients were seen in follow-up every 3 to 6 months for an average follow-up period of 16 months. The primary endpoint was device-related infection. A total of 110 patients were treated with preoperative antibiotics only (group 1), whereas 257 patients received both preoperative and postoperative antibiotics (group 2). After a mean follow-up period of 16 months, 1 patient in group 1 (0.9%) and 4 patients in group 2 (1.5%) experienced a device-related infection. There was no significant difference in the rate of infection between the 2 groups (P = 0.624). In the univariate analysis, only the age (60 ± 11 vs 75 ± 12 years, P antibiotics had a similar rate of infection as those treated with preoperative antibiotics alone. Further studies are needed to confirm these preliminary findings. © 2017 Wiley Periodicals, Inc.

  18. [Nevirapine related hepatotoxicity: the prevalence and risk factors in a cohort of ART naive Han Chinese with AIDS].

    Science.gov (United States)

    Gao, Shi-cheng; Gui, Xi-en; Deng, Li-ping; Zhang, Yong-xi; Yan, Ya-jun; Rong, Yu-ping; Liang, Ke; Yang, Rong-rong

    2010-09-01

    To investigate the incidence of hepatotoxicity in acquired immunodeficiency syndrome (AIDS) patients on combined anti-retroviral therapy (cART) containing nevirapine (NVP) and to assess the risk factors and its impact on cART. 330 AIDS patients from March 2003 to June 2008 at local county were enrolled and a retrospective study using Kaplan-meier survival and Multivariate logistic regression modeling was conducted. 267 out of 330 patients received NVP based cART and 63 cases received EFV-based cART. The deference of prevalences of hepatotoxicity between the two groups is statistically significant (Chi2 = 6.691, P = 0.01). 133 out of 267 (49.8%) patients on NVP based cART had at least one episode of ALT elevation during a median 21 months (interquartile ranges, IQR 6, 37) follow-up time, amounts for 28.5 cases per 100 person-years. Baseline ALT elevation (OR = 14.368, P = 0.017)and HCV co-infection (OR = 3.009, P = 0.000) were risk factors for cART related hepatotoxicity, while greatly increased CD4+ T(CD4) cell count was protective against hepatotoxicity development (OR = 0.996, P = 0.000). Patients co-infected with HCV received NVP-based cART had the higher probability of hepatotoxicity than those without HCV co-infection (Log rank: Chi2 = 16.764, P = 0.000). 23 out of the 133 subjects (17.3%) with NVP related hepatotoxicity discontinued cART temporarily or shifted NVP to efavirenz. NVP related hepatotoxicity was common among ARV naive HIV infected subjects in our cohort. Baseline ALT elevation and HCV co-infection were associated statistically with the development of hepatotoxicity. Hepatotoxicity led to discontinuing cART temporarily or switching to other regimens in some subjects. It suggested that NVP should be used with caution in patients co-infected with HCV among whom anti-HCV therapy before cART initiation may contribute to minimizing the probability of NVP associated hepatotoxicity.

  19. Should patients with Björk-Shiley valves undergo prophylactic replacement?

    Science.gov (United States)

    Birkmeyer, J D; Marrin, C A; O'Connor, G T

    1992-08-29

    About 85,000 patients have undergone replacement of diseased heart valves with prosthetic Björk-Shiley convexo-concave (CC) valves. These valves are prone to fracture of the outlet strut, which leads to acute valve failure that is usually fatal. Should patients with these valves undergo prophylactic replacement to avoid fracture? The incidence of strut fracture varies between 0% and 1.5% per year, depending on valve opening angle (60 degrees or 70 degrees), diameter (less than 29 mm or greater than or equal to 29 mm), and location (aortic or mitral). Other factors include the patient's life expectancy and the expected morbidity and mortality associated with reoperation. We have used decision analysis to identify the patients most likely to benefit from prophylactic reoperation. The incidence of outlet strut fracture was estimated from the data of three large studies on CC valves, and stratified by opening angle, diameter, and location. A Markov decision analysis model was used to estimate life expectancy for patients undergoing prophylactic valve replacement and for those not undergoing reoperation. Prophylactic valve replacement does not benefit patients with CC valves that have low strut fracture risks (60 degrees aortic valves and less than 29 mm, 60 degrees mitral valves). For most patients with CC valves that have high strut fracture risks (greater than or equal to 29 mm, 70 degrees CC), prophylactic valve replacement increases life expectancy. However, elderly patients with such valves benefit from prophylactic reoperation only if the risk of operative mortality is low. Patient age and operative risk are most important in recommendations for patients with CC valves that have intermediate strut fracture risks (less than 29 mm, 70 degrees valves and greater than or equal to 29 mm, 60 degrees mitral valves). For all patients and their doctors facing the difficult decision on whether to replace CC valves, individual estimates of operative mortality risk that

  20. Tuberculous abdominal abscess in an HIV-infected man: Neither infection previously diagnosed

    Directory of Open Access Journals (Sweden)

    Kuo-Yao Kao

    2010-11-01

    Full Text Available A 38-year-old man had a 1-week history of right lower quadrant abdominal pain; the initial impression was that he had diverticulitis of the ascending colon with an intra-abdominal abscess. Signs of peritonitis mandated an immediate right hemicolectomy. The unusual location of the abscess and the patient’s unusual postoperative course suggested that he might also have a systemic disease. Testing for HIV infection was positive. After 2 weeks in hospital, he was treated as an outpatient for both tuberculosis and HIV with a favourable outcome. In Taiwan a pre-operative HIV test is not performed routinely, and the HIV seroprevalence in surgical patient populations is unknown. Surgeons should keep the possibility of HIV infection in mind in a patient with an unusual clinical course.

  1. Effect of HIV Infection on Human Papillomavirus Types Causing Invasive Cervical Cancer in Africa

    Science.gov (United States)

    de Vuyst, Hugo; Tenet, Vanessa; Plummer, Martyn; Tully, Stephen; Franceschi, Silvia

    2016-01-01

    Objectives: HIV infection is known to worsen the outcome of cervical human papillomavirus (HPV) infection and may do so differentially by HPV type. Design: Twenty-one studies were included in a meta-analysis of invasive cervical cancers (ICC) among women infected with HIV in Africa. Method: Type-specific HPV DNA prevalence was compared with data from a similar meta-analysis of HIV-negative ICC using prevalence ratios (PR). Results: HPV detection was similar in 770 HIV-positive (91.2%) and 3846 HIV-negative (89.6%) ICC, but HIV-positive ICC harbored significantly more multiple HPV infections (PR = 1.75, 95% confidence intervals: 1.18 to 2.58), which were significantly more prevalent in ICC tested from cells than from biopsies. HPV16 was the most frequently detected type in HIV-positive ICC (42.5%), followed by HPV18 (22.2%), HPV45 (14.4%), and HPV35 (7.1%). Nevertheless, HIV-positive ICC were significantly less frequently infected with HPV16 than HIV-negative ICC (PR = 0.88, 95% confidence intervals: 0.79 to 0.99). Other high-risk types were significantly more prevalent in HIV-positive ICC, but only for HPV18 was there a significantly higher prevalence of both single and multiple infections in HIV-positive ICC. Increases for other high-risk types were primarily accounted for by multiple infections. The proportion of HPV-positive ICC estimated attributable to HPV16/18 (71.8% in HIV positive, 73.4% in HIV negative) or HPV16/18/31/33/45/52/58 (88.8%, 89.5%) was not affected by HIV. Conclusions: HIV alters the relative carcinogenicity of HPV types, but prophylactic HPV16/18 vaccines may nevertheless prevent a similar proportion of ICC, irrespective of HIV infection. PMID:27331659

  2. Lessons on Stigma: Teaching about HIV/AIDS

    Science.gov (United States)

    Lichtenstein, Bronwen; DeCoster, Jamie

    2014-01-01

    Teaching about the sociology of HIV/AIDS involves teaching about the causes and effects of stigma. We describe a Sociology of HIV/AIDS course at the University of Alabama in which stigma reduction was assessed as a primary objective. The syllabus involved theory-based instruction, class visits, service learning, and student research on community…

  3. CERN Technical Training: available Places in forthcoming Courses

    CERN Multimedia

    HR Department

    2009-01-01

    The following course sessions are scheduled in the framework of the 2009 CERN Technical Training Programme and places are still available. You can find the full updated Technical Training course programme in our web catalogue (http://cta.cern.ch/cta2/f?p=110:9). OFFICE SOFTWARE Novelties Office 2007 : Word 2007\t(Français)\t11.05\t1 jour Secure e-mail and Web browsing\t(Français)\t19.05\t1.5 heure Outlook 2007 (Short Course 1) – E-mail\t(Bilingual)\t25.05\t3 hours Outlook 2007 (Short Course II) – Calendar, Tasks and Notes (Bilingual)\t25.05\t3 hours Outlook 2007 (Short Course III) – Meetings and Delegation (Bilingual)\t26.05\t3 hours Word 2007 (Short Course II) – HowTo…Mail merge (with Outlook)\t(Bilingual)\t26.05\t3 hours Word 2007 (Short Course III) - Working with long documents: Styles and tables of content\t(Bilingual)\t28.05\t3 hours Indico – Meeting Organization\t(English)\t05.06\t2 hours Indico – Conference Organization\t(Français)\t05.06\t3 hours Excel 2007 (Short Course I) –HowTo…Work with formulae (...

  4. CERN Technical Training: available Places in forthcoming Courses

    CERN Multimedia

    HR Department

    2009-01-01

    The following course sessions are scheduled in the framework of the 2009 CERN Technical Training Programme and places are still available. You can find the full updated Technical Training course programme in our web catalogue (http://cta.cern.ch/cta2/f?p=110:9). OFFICE SOFTWARE Novelties Office 2007 : Word 2007\t(Français)\t11.05\t1 jour Secure e-mail and Web browsing\t(Français)\t19.05\t1.5 heure Outlook 2007 (Short Course 1) – E-mail\t(Bilingual)\t25.05\t3 hours Outlook 2007 (Short Course II) – Calendar, Tasks and Notes (Bilingual)\t25.05\t3 hours Outlook 2007 (Short Course III) – Meetings and Delegation (Bilingual)\t26.05\t3 hours Word 2007 (Short Course II) – HowTo…Mail merge (with Outlook)\t(Bilingual)\t26.05\t3 hours Word 2007 (Short Course III) - Working with long documents: Styles and tables of content\t(Bilingual)\t28.05\t3 hours Indico – Meeting Organization\t(English)\t05.06\t2 hours Indico – Conference Organization\t(Français)\t05.06\t3 hours Excel 2007 (Short Course I) –HowTo…Work with formulae\t(...

  5. Pneumocystis Pneumonia in Non-HIV Pregnant Women Receiving Chemotherapy for Malignant Lymphoma: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Yuki Fukutani

    2017-01-01

    Full Text Available Pneumocystis pneumonia (PCP is a life-threatening opportunistic infection that sometimes occurs in immunocompromised patients with human immunodeficiency virus (HIV. Here, we report two extremely rare cases of PCP in non-HIV pregnant women who underwent chemotherapy for malignant lymphoma. Case  1 is a 34-year-old primigravida who was diagnosed with Hodgkin’s lymphoma. She received ABVD chemotherapy and developed PCP at 37 weeks of gestation. After the onset of PCP, emergent cesarean section was performed due to a nonreassuring fetal status. Case  2 is a 31-year-old multigravida with diffuse large B-cell lymphoma who was administered R-CHOP chemotherapy. At 34 weeks of gestation, she complained of dyspnea and developed PCP. She delivered her baby vaginally immediately after the onset of symptoms. Both patients were treated with sulfamethoxazole-trimethoprim (ST and recovered shortly thereafter. The babies’ courses were also uneventful. PCP remains a serious cause of death, especially in non-HIV patients, and, therefore, appropriate prophylaxis and a prompt diagnosis are imperative.

  6. Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study.

    Directory of Open Access Journals (Sweden)

    Phairote Teeranaipong

    Full Text Available Etravirine(ETR can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV. However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV- and nevirapine(NVP-based regimens.Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database.1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01. K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01. The results from all three scoring systems were concordant. 165(11.1% and 161(10.9% patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85. 195 (32.2% and 191 (31.6% patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79. The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01.The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.

  7. Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study.

    Science.gov (United States)

    Teeranaipong, Phairote; Sirivichayakul, Sunee; Mekprasan, Suwanna; Ohata, Pirapon June; Avihingsanon, Anchalee; Ruxrungtham, Kiat; Putcharoen, Opass

    2016-01-01

    Etravirine(ETR) can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV). However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV)- and nevirapine(NVP)-based regimens. Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs) were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database. 1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01). K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01). The results from all three scoring systems were concordant. 165(11.1%) and 161(10.9%) patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85). 195 (32.2%) and 191 (31.6%) patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79). The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01). The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.

  8. HIV status and hearing loss among children between 6 and 12 years of age at a large urban health facility in south western Uganda.

    Science.gov (United States)

    Nakku, Doreen; Nyaiteera, Victoria; Llowet, Evelyn; Nanseera, Dennis; Nakalema, Gladys; Westerberg, Brian; Bajunirwe, Francis

    2017-10-01

    Pediatric HIV infection and treatment may increase the risk for hearing loss (HL), both sensorineural (SNHL) and conductive hearing loss (CHL). There is limited data on this subject, especially from sub Saharan Africa. The aim of this study was therefore to compare the prevalence of hearing loss among HIV positive and negative children, to determine the types of hearing loss and whether Nevirapine (NVP) based antiretroviral therapy (ART) is associated with HL. We conducted a cross sectional study at two tertiary health facilities in south western Uganda. We consecutively enrolled 79 HIV negative and 148 HIV positive children aged between 6 and 12 years. Inclusion criteria were completion of written consent, ability to follow instructions to perform an audiogram and absence of congenital HL. We conducted hearing screening using the iPad Shoebox ® audiometer, and confirmatory assessments were conducted using pure tone audiometry. Hearing was classified as either normal hearing, CHL, SNHL or mixed. Of the 227 children enrolled, 115 (50.7%) were female. The mean age was 9.2 years (median = 9). Based on self-report, frequency of HL among HIV positive children was 6.8% and 20.3% among HIV negative children (p=children was 8.8% compared to 10.1% among the HIV negative children (p = 0.74). CHL was generally more frequent than SNHL but SNHL occurred more frequently among HIV positive (7.4%) compared to HIV negative children (3.8%). No association was found between NVP based ART and HL (p = 0.41). Logistic regression showed that older age of the child (p = 0.01), previous ear infection (p=children. Older age of the child, previous ear infection, use of TB drugs and long duration on ART among the HIV positive children increase the odds of having hearing loss among children. However, use of NVP was not associated with HL. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.

    Science.gov (United States)

    Mbuagbaw, Lawrence; Mursleen, Sara; Irlam, James H; Spaulding, Alicen B; Rutherford, George W; Siegfried, Nandi

    2016-12-10

    The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010. To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children. We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009. We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination.The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure

  10. [Therapeutic-prophylactic milk products with a new immunocorrector of natural origin].

    Science.gov (United States)

    Besednova, N N; Epshteĭn, L M; Gazha, A K; Borovskaia, G A; Besednov, A L; Rozhzhov, I V; Smolina, T P

    1997-01-01

    Authors had received and investigated on experiment milk medical and prophylactic products (milk and kefir) with addition peptide, obtained from nervous tissue of squids. It has been established that addition of gangliin to the milk and kefir causes stimulation cellular and humoral factors of immunity answer at laboratory animals. Medical and prophylactic milk products with gangliin return to the normal state reduced immunity indexes of the mice with experimental immunodeficits.

  11. Prophylactic central lymph nodes dissection (VI level in papillary thyroid cancer

    Directory of Open Access Journals (Sweden)

    Pavel Olegovich Rumiantsev

    2015-05-01

    Full Text Available Metastatic involvement of central lymph nodes in patients with papillary thyroid cancer (PTC is very common. However, prophylactic central lymph nodes dissection additionally to thyroidectomy does not significantly affect disease-free and overall survival of PTC patients. Meanwhile its routine conduction is tangibly increase postsurgical complications. From efficacy/safety point of view prophylactic central lymph nodes dissection couldn't be recommended as substantiated in all PTC patients.

  12. Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Paul W Denton

    2008-01-01

    Full Text Available Worldwide, vaginal transmission now accounts for more than half of newly acquired HIV-1 infections. Despite the urgency to develop and implement novel approaches capable of preventing HIV transmission, this process has been hindered by the lack of adequate small animal models for preclinical efficacy and safety testing. Given the importance of this route of transmission, we investigated the susceptibility of humanized mice to intravaginal HIV-1 infection.We show that the female reproductive tract of humanized bone marrow-liver-thymus (BLT mice is reconstituted with human CD4+ T and other relevant human cells, rendering these humanized mice susceptible to intravaginal infection by HIV-1. Effects of HIV-1 infection include CD4+ T cell depletion in gut-associated lymphoid tissue (GALT that closely mimics what is observed in HIV-1-infected humans. We also show that pre-exposure prophylaxis with antiretroviral drugs is a highly effective method for preventing vaginal HIV-1 transmission. Whereas 88% (7/8 of BLT mice inoculated vaginally with HIV-1 became infected, none of the animals (0/5 given pre-exposure prophylaxis of emtricitabine (FTC/tenofovir disoproxil fumarate (TDF showed evidence of infection (Chi square = 7.5, df = 1, p = 0.006.The fact that humanized BLT mice are susceptible to intravaginal infection makes this system an excellent candidate for preclinical evaluation of both microbicides and pre-exposure prophylactic regimens. The utility of humanized mice to study intravaginal HIV-1 transmission is particularly highlighted by the demonstration that pre-exposure prophylaxis can prevent intravaginal HIV-1 transmission in the BLT mouse model.

  13. Late presentation to HIV care despite good access to health services

    DEFF Research Database (Denmark)

    Darling, Katharine Ea; Hachfeld, Anna; Cavassini, Matthias

    2016-01-01

    infection rates are rising, and diagnosing HIV early in the course of infection remains a challenge. Late presentation to care in HIV refers to individuals newly presenting for HIV care with a CD4 count below 350 cells/µl or with an acquired immune deficiency syndrome (AIDS)-defining event. Late...

  14. First UK case report of kidney transplantation from an HIV-infected deceased donor to two HIV-infected recipients.

    Science.gov (United States)

    Nolan, Eileen; Karydis, Nikolaos; Drage, Martin; Hilton, Rachel

    2018-04-01

    Kidney transplantation is now considered the treatment of choice for many human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD). Graft survival rates using HIV-negative donors and carefully selected HIV-positive ESRD patients are similar to those observed in HIV-uninfected kidney transplant recipients. To address the relative shortfall in donated organs it has been proposed that organs from HIV-infected deceased donors might be allocated to HIV-infected patients on the transplant waiting list. Preliminary experience in South Africa reports promising short-term outcomes in a small number of HIV-infected recipients of kidney transplants from HIV-infected donors. We sought to replicate this experience in the UK by accepting kidney offers from HIV infected deceased donors for patients with HIV-infection on the kidney transplant waiting list. Here we report the UK's first cases of kidney transplantation between HIV-positive donors and recipients.

  15. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study

    NARCIS (Netherlands)

    Montaner, J. S.; Reiss, P.; Cooper, D.; Vella, S.; Harris, M.; Conway, B.; Wainberg, M. A.; Smith, D.; Robinson, P.; Hall, D.; Myers, M.; Lange, J. M.

    1998-01-01

    CONTEXT: Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving

  16. Nelfinavir and nevirapine side effects during pregnancy

    NARCIS (Netherlands)

    Timmermans, S; Tempelman, C; Godfried, MH; Nellen, J; Sprenger, H; Schneider, MEE; de Wolf, F; Boer, K; van der Ende, Marchina E.

    2005-01-01

    Background: The risk of vertical transmission of HIV has been substantially reduced since the introduction of highly active antiretroviral therapy (HAART); however, the impact of taking HAART during pregnancy on the woman, the fetus and the infant is not yet understood. Objective: To assess and

  17. Nelfinavir and nevirapine side effects during pregnancy

    NARCIS (Netherlands)

    Timmermans, Sarah; Tempelman, Claire; Godfried, Mieke H.; Nellen, Jeanine; Dieleman, Jeanne; Sprenger, Herman; Schneider, Margriet Ee; de Wolf, Frank; Boer, Kees; van der Ende, Marchina E.

    2005-01-01

    BACKGROUND: The risk of vertical transmission of HIV has been substantially reduced since the introduction of highly active antiretroviral therapy (HAART); however, the impact of taking HAART during pregnancy on the woman, the fetus and the infant is not yet understood. OBJECTIVE: To assess and

  18. CERN Technical Training: Autumn 2007 Course Catalogue

    CERN Multimedia

    2007-01-01

    The following course sessions are scheduled in the framework of the CERN Technical Training Program 2007. You may find the full updated Technical Training course programme in our web-catalogue. OFFICE SOFTWARE CERN EDMS MTF en pratique F 4.9 1/2 d WORD 2007 (Short Course III) - How to work with long documents E/F 14.9 1/2 d FrontPage 2003 - niveau 1 E/F 17-18.9 2 d WORD 2007 - Niveau1: ECDL F 20.-21-9 2 d ACCESS 2007 - Level 1: ECDL E 20-21.9 2 d EXCEL 2007 (Short Course I) - How to work with Formulae E/F 21.9 1/2 d CERN EDMS Introduction E 24.9 1 d Java 2 Enterprise Edition - Part 1: Web Applications E 24-25.9 2 d Outlook 2007 (Short Course II) - Calendar, Tasks and Notes E/F 28.9 1/2 d Outlook 2007 (Short Course III) - Meeting and Delegation ...

  19. A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

    NARCIS (Netherlands)

    Paredes, Roger; Puertas, Maria Carmen; Bannister, Wendy; Kisic, Mónica; Cozzi-Lepri, Alessandro; Pou, Christian; Bellido, Rocío; Betancor, Gilberto; Bogner, Johannes; Gargalianos, Panagiotis; Bánhegyi, Dénes; Clotet, Bonaventura; Lundgren, Jens; Menéndez-Arias, Luis; Martinez-Picado, Javier; Losso, M.; Elias, C.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Suetnov, O.; Clumeck, N.; de Wit, S.; Poll, B.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Rozsypal, H.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A.-B. E.; Skinhøj, P.; Pedersen, C.; Oestergaard, L.; Zilmer, K.; Ristola, M.; Katlama, C.; Viard, J.-P.; Girard, P.-M.; Livrozet, J. M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Rockstroh, J.; Schmidt, R.; van Lunzen, J.; Degen, O.; Stellbrink, H. J.; Staszewski, S.; Fätkenheuer, G.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Perdios, J.; Panos, G.; Filandras, A.; Karabatsaki, E.; Sambatakou, H.; Banhegyi, D.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Pollack, S.; Hassoun, G.; Maayan, S.; Vella, S.; Esposito, R.; Mazeu, I.; Mussini, C.; Arici, C.; Pristera, R.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Chirianni, A.; Montesarchio, E.; Gargiulo, M.; Antonucci, G.; Iacomi, F.; Narciso, P.; Vlassi, C.; Zaccarelli, M.; Lazzarin, A.; Finazzi, R.; Galli, M.; Ridolfo, A.; d'Arminio, A.; Rozentale, B.; Aldins, P.; Chaplinskas, S.; Hemmer, R.; Staub, T.; Reiss, P.; Ormaasen, V.; Maeland, A.; Brunn, J.; Knysz, B.; Gasiorowski, J.; Horban, A.; Bakowska, E.; Prokopowicz, D.; Flisiak, R.; Boron-Kaczmarska, A.; Pynka, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Antunes, F.; Valadas, E.; Mansinho, K.; Maltez, F.; Duiculescu, D.; Rakhmanova, A.; Vinogradova, E.; Buzunova, S.; Jevtovic, D.; Mokrás, M.; Staneková, D.; Tomazic, J.; González-Lahoz, J.; Soriano, V.; Martin-Carbonero, L.; Labarga, P.; Moreno, S.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miró, J. M.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Karlsson, A.; Persson, P. O.; Ledergerber, B.; Weber, R.; Francioli, P.; Cavassini, M.; Hirschel, B.; Boffi, E.; Furrer, H.; Battegay, M.; Elzi, L.; Kravchenko, E.; Chentsova, N.; Kutsyna, G.; Servitskiy, S.; Krasnov, M.; Barton, S.; Johnson, A. M.; Mercey, D.; Phillips, A.; Johnson, M. A.; Murphy, M.; Weber, J.; Scullard, G.; Fisher, M.; Leen, C.; Gatell, J.; Gazzard, B.; Lundgren, J.; d'Arminio Monforte, A.; Kirk, O.; Mocroft, A.; Cozzi-Lepri, A.; Grint, D.; Ellefson, M.; Podlekareva, D.; Kjaer, J.; Peters, L.; Reekie, J.; Kowalska, J.; Tverland, J.; Fischer, A. H.

    2011-01-01

    The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who

  20. The use of prophylactic antibiotics in plastic surgery: update in 2010.

    Science.gov (United States)

    Hauck, Randy M; Nogan, Stephen

    2013-01-01

    The indications for prophylactic antibiotics in plastic surgery remain controversial. No recent survey has been reported on the use of prophylactic antibiotics by plastic surgeons in clinical practice. This survey was designed to assess the current use of prophylactic antibiotics by plastic surgeons and to compare trends with previous studies. All members of the American Society of Plastic Surgeons with an e-mail address on the Society's website were contacted via an e-mail and sent a link to a SurveyMonkey questionnaire. To survey only in those subspecialty areas that they practice in, surgeons were queried only on the procedures that they perform. Within each section, a list of common representative procedures was included, with questions about the use of antibiotic prophylaxis. A total of 3824 American Society of Plastic Surgeons members were contacted. Of the 3613, 910 with working e-mail addresses responded to the survey for a response rate of 25%. And 833 or 91.5% completed the survey. Survey data cover the percentage of surgeons reporting their use of antibiotics in procedures that they currently perform. The percentage of plastic surgeons who use prophylactic antibiotics in almost all procedures studied has increased significantly when compared with earlier studies. The use of prophylactic antibiotics by plastic surgeons has increased considerably since the prior studies by Krizek et al (Plast Reconstr Surg. 1975;55:21-32 and 1985;76:953-963). Some of these uses are appropriate because of the use in procedures involving implants and longer operations. The elevated rates for clean procedures are not part of the evidence-based practice.

  1. Neurologic complications of intrathecal liposomal cytarabine administered prophylactically to patients with non-Hodgkin lymphoma.

    Science.gov (United States)

    Gállego Pérez-Larraya, Jaime; Palma, José Alberto; Carmona-Iragui, María; Fernández-Torrón, Roberto; Irimia, Pablo; Rodríguez-Otero, Paula; Panizo, Carlos; Martínez-Vila, Eduardo

    2011-07-01

    Central nervous system (CNS) prophylaxis is required during initial treatment of non-Hodgkin lymphoma (NHL) subtypes that carry a high risk of CNS involvement. Intrathecal (IT) liposomal cytarabine, a formulation with prolonged half-life, has been shown to be safe and effective in the treatment of meningeal disease in patients with high-grade lymphoma. We retrospectively reviewed all adult patients with high-grade NHL that received prophylactic therapy with IT liposomal cytarabine and developed neurologic complications in our institution between April 2007 and May 2009. We recorded information on hospital admission, chemotherapy regimens, clinical features, neuroimaging, cerebrospinal fluid, neurophysiology data, and outcome. Neurotoxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Four of fourteen patients (28%) developed moderate or severe neurotoxicity (grades 2 and 3 of the NCI-CTC), manifested as conus medullaris/cauda equine syndrome or pseudotumour cerebri-like syndrome, after a median of 3.5 IT courses of liposomal cytarabine. All patients had received corticosteroids to prevent arachnoiditis. Liposomal cytarabine given via the IT route, even with concomitant corticosteroid administration, can result in significant neurotoxicity in some patients. We discuss the potential pathogenesis of these effects and suggest hypothetical therapeutic measures to prevent these complications. Specialists should be aware of these possible complications when administering prophylactic IT liposomal cytarabine in high-grade NHL patients, and additional prospective studies should be conducted to more clearly delineate the frequency and characteristics of these complications.

  2. ART drugs help reduce HIV transmission, Chinese study finds ...

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

    International Development Research Centre Government of Canada ... ART drugs help reduce HIV transmission, Chinese study finds ... where only one person has HIV can reduce HIV transmission rates, at least in the short term, a Chinese study has found. ... Ecohealth Field-building Leadership Initiative in Southeast Asia.

  3. Maternal antiretroviral therapy for the prevention of mother-to-child transmission of HIV in Malawi: maternal and infant outcomes two years after delivery.

    Directory of Open Access Journals (Sweden)

    Marina Giuliano

    Full Text Available Optimized preventive strategies are needed to reach the objective of eliminating pediatric AIDS. This study aimed to define the determinants of residual HIV transmission in the context of maternal antiretroviral therapy (ART administration to pregnant women, to assess infant safety of this strategy, and to evaluate its impact on maternal disease.A total of 311 HIV-infected pregnant women were enrolled in Malawi in an observational study and received a nevirapine-based regimen from week 25 of gestation until 6 months after delivery (end of breastfeeding period if their CD4+ count was > 350/mm(3 at baseline (n = 147, or indefinitely if they met the criteria for treatment (n. 164. Mother/child pairs were followed until 2 years after delivery. The Kaplan-Meier method was used to estimate HIV transmission, maternal disease progression, and survival at 24 months. The rate of HIV infant infection was 3.2% [95% confidence intervals (CI 1.0-5.4]. Six of the 8 transmissions occurred among mothers with baseline CD4+ count > 350/mm(3. HIV-free survival of children was 85.8% (95% CI 81.4-90.1. Children born to mothers with baseline CD4+ count < 350/mm(3 were at increased risk of death (hazard ratio 2.6, 95% CI 1.1-6.1. Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm(3 was 20.6% (95% CI 9.2-31.9 by 18 months of drug discontinuation.HIV transmission in this cohort was rare however, it occurred in a significative proportion among women with high CD4+ counts. Strategies to improve treatment adherence should be implemented to further reduce HIV transmission. Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage. Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered.

  4. Aesthetic outcome, patient satisfaction, and health-related quality of life in women at high risk undergoing prophylactic mastectomy and immediate breast reconstruction.

    Science.gov (United States)

    Isern, A E; Tengrup, I; Loman, N; Olsson, H; Ringberg, A

    2008-10-01

    Prophylactic mastectomy is an effective risk-reducing option in women with hereditary increased risk of breast cancer. It may be combined with immediate reconstruction, with the intention of improving aesthetic outcome and health-related quality of life. Sixty-one women underwent prophylactic mastectomy and immediate breast reconstruction in Malmö, Sweden, between 1995 and 2003. Forty women underwent bilateral prophylactic mastectomy and immediate reconstruction. Ten of these had a previous breast cancer diagnosis. Twenty-one women underwent contralateral prophylactic mastectomy and immediate reconstruction after a previous breast cancer. Fifty-four of the women (89%) were evaluated clinically for aesthetic results and complications. Patient satisfaction and quality of life were evaluated with one study-specific and two standardised health-related questionnaires administered at time of clinical follow-up. Median follow-up time was 42 months (range 7-99 months). The position of the reconstructed breasts was judged as satisfactory in 77% of breasts. Symmetry in relation to the midline was adequate in 89% of breasts. A capsular contracture grade III according to Baker and indentation tonometry was observed in 1% of breasts (1/104). The complication rate was 18% (7% early and 11% late). Secondary corrections were carried out in 11% of breasts. The study-specific questionnaire revealed a high degree of satisfaction. No woman regretted the procedure, and all women would have chosen the same type of surgery again. An age-stratified comparison of Swedish women using the Short Form 36 Health Survey Questionnaire (SF-36) questionnaire was carried out for this study. The study population scores were high, suggesting that prophylactic mastectomy and immediate reconstruction on both physical and psychological issues in this retrospective study had no negative effect. Also, the Hospital Anxiety and Depression Scale (HAD) questionnaire did not suggest any increased anxiety or

  5. Technical Training: CERN Technical Training 2004 - New Short Courses (SC) on Microsoft Outlook

    CERN Multimedia

    Monique Duval

    2004-01-01

    The CERN Technical Training programme is now proposing a new format for courses on Microsoft Outlook. Three two-hours Short Courses (SC) will cover basic and advanced functionalities of the recommended mail client for email at CERN. Each module can be followed independently. The next scheduled sessions will take place as follows: Outlook (SC I): E-mail. Next session: 31.8.2004 (9h00-11h00) Outlook (SC II): Calendar, Tasks and Notes. Next session: 31.8.2004 (14h00-16h00) Outlook (SC III): Meetings and Delegation. Next session: 7.9.2004 (14h00-16h00) In particular, SC I will cover how to open, create and send email, work with attachments, use stationery, organise mail, and work with the address book, SC II will show how to work with the calendar, tasks and notes, and SC III will cover how to organise and manage meetings, work with meeting requests, share tasks, and use email and calendar delegation. The number of participants to each session is limited to 8. The instructor is English-French bilingual, and s...

  6. Occupational exposure to HIV: a conflict situation for health workers.

    Science.gov (United States)

    Kumakech, E; Achora, S; Berggren, V; Bajunirwe, F

    2011-12-01

    To determine the frequency of occupational exposure to human immunodeficiency virus (HIV), the circumstances and predisposing factors, the high-risk groups, the extent to which exposures are reported and the post-exposure prophylaxis (PEP) utilized by health-care workers (HCWs) and students in a Ugandan hospital. Occupational exposure to HIV is a low but potential risk of HIV infection to health workers. Self-administered questionnaire was given to 224 participants (including 98 HCWs and 126 students) in Mbarara Hospital, Uganda. Data were analysed with descriptive statistics using the Statistical Package for the Social Sciences version 15.0 (SPSS Inc, Chicago, IL, USA). Of the 224 participants surveyed, 19.2% reported having sustained injection needle stick injuries in the previous year, of which 4.46% occurred with HIV-infected blood. Other reported injuries were cannula needle stick injury (0.89%), suture needle stick injuries (3.13%), scalpel cut injuries (0.45%) and muco-cutaneous contamination (10.27%). The most affected groups were nurses-midwives for scalpel injuries and students for stick injuries. The predisposing factors reported included lack of protective devices and recapping of needles. Exposures were under-reported. Uptake of PEP was also low. Occupational exposure to HIV presents a conflict situation for HCWs. It remains a frequent occurrence particularly among student nurses-midwives, despite being avoidable. Its prophylactic treatment is hampered by poor reporting and investigation of exposures, and poor access to PEP. Strict adherence to universal precaution and proper handling of occupational exposure to HIV should be encouraged. © 2011 The Authors. International Nursing Review © 2011 International Council of Nurses.

  7. Does Content Matter? Analyzing the Change in Global Awareness between Business- and Nonbusiness-Focused Short-Term Study Abroad Courses

    Science.gov (United States)

    DeLoach, Stephen B.; Kurt, Mark; Olitsky, Neal H.

    2015-01-01

    Business schools have long sought to increase students' global awareness. Short-term study abroad (STSA) experiences are becoming increasingly popular ways of generating awareness. While a handful of studies have found evidence of efficacy, none have specifically tested how courses with business content differ from other STSAs. Using a…

  8. HIV-1 Immunogen: an overview of almost 30 years of clinical testing of a candidate therapeutic vaccine.

    Science.gov (United States)

    Graziani, Gina M; Angel, Jonathan B

    2016-07-01

    Although current antiretroviral therapy (ART) has transformed HIV infection into a chronic, manageable disease, ART does not cure HIV infection. Furthermore, the majority of the world's infected individuals live in resource-limited countries in which access to ART is limited. Thus, the development of an effective therapeutic HIV vaccine would be an invaluable treatment alternative. Developed by the late Dr. Jonas Salk, HIV-1 Immunogen (Remune®) is a candidate therapeutic vaccine that has been studied in thousands of HIV-infected individuals in more than a dozen clinical trials during almost three decades. This Drug Evaluation, which summarizes the results of these trials that have shown the vaccine to be safe and immunogenic, also discusses the contradictory and controversial conclusions drawn from the phases 2, 2/3 and 3 trials that assessed the clinical efficacy of this vaccine. Given the lack of unequivocal clinical benefits of HIV-1 Immunogen despite almost 30 years of extensive testing, it does not appear, in our view, that this vaccine is a clinically effective immunotherapy. However, inclusion of this vaccine in the newly proposed 'Kick/Shock and Kill' strategy for HIV eradication, or use as a prophylactic vaccine, could be considered for future trials.

  9. Prophylactic Anticonvulsants in patients with brain tumour

    International Nuclear Information System (INIS)

    Forsyth, P.A.; Weaver, S.; Fulton, D.

    2003-01-01

    We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need ≥900 patients to have a suitably powered study. These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure. (author)

  10. Prophylactic Anticonvulsants in patients with brain tumour

    Energy Technology Data Exchange (ETDEWEB)

    Forsyth, P.A. [Depts. of Oncology and Clinical Neurosciences, Univ. of Calgary, Calgary, Alberta (Canada); Tom Baker Cancer Centre, Calgary, Alberta (Canada); Weaver, S. [Depts. of Neurology and Medicine, Albany Medical College, Albany, New York (United States); Fulton, D. [Dept. of Radiation Oncology, Cross Cancer Institute and Dept. of Medicine/Neurology, Univ. of Alberta, Edmonton, Alberta (Canada)

    2003-05-01

    We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need {>=}900 patients to have a suitably powered study. These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure. (author)

  11. HIV/AIDS status disclosure increases support, behavioural change and, HIV prevention in the long term: a case for an Urban Clinic, Kampala, Uganda.

    Science.gov (United States)

    Atuyambe, Lynn Muhimbuura; Ssegujja, Eric; Ssali, Sarah; Tumwine, Christopher; Nekesa, Nicolate; Nannungi, Annette; Ryan, Gery; Wagner, Glenn

    2014-06-21

    Disclosure of HIV status supports risk reduction and facilitates access to prevention and care services, but can be inhibited by the fear of negative repercussions. We explored the short and long-term outcomes of disclosure among clients attending an urban HIV clinic in Uganda. Qualitative semi-structured interviews were administered to a purposeful sample of 40 adult HIV clients that was stratified by gender. The information elicited included their lived experiences and outcomes of disclosure in the short and long term. A text data management software (ATLAS.ti) was used for data analysis. Codes were exported to MS Excel and pivot tables, and code counts made to generate statistical data. Of the 134 short-term responses elicited during the interview regarding disclosure events, most responses were supportive including encouragement, advice and support regarding HIV care and treatment. The results show on-disclosing to spouse, there was more trust, and use of condoms for HIV prevention. Only one third were negative responses, like emotional shock and feeling of distress. The negative reactions to the spouses included rejection, shock and distress in the short term. Even then, none of these events led to drastic change such as divorce. Other responses reflected HIV prevention and call for behavioural change and advice to change sexual behaviour, recipient seeking HIV testing or care. Women reported more responses of encouragement compared to men. Men reported more preventive behaviour compared to women. Of the 137 long-term outcomes elicited during disclosure, three quarters were positive followed by behavioral change and prevention, and then negative responses. Men reported increased care and support when they disclosed to fellow men compared to when women disclosed to women. There was better or not change in relationship when women disclosed to women than when women disclosed to men. There is overwhelming support to individuals that disclose their HIV status

  12. The role of splenic irradiation in treating HIV-associated immune thrombocytopenia

    International Nuclear Information System (INIS)

    Blauth, Jeanette; Fisher, Scot; Henry, David; Nichini, Franco

    1999-01-01

    Purpose: To evaluate our experience in treating patients with HIV-associated thrombocytopenia using splenic irradiation. Methods and Materials: From 1993 to 1998, 10 patients with HIV-related immune thrombocytopenia (ITP) were treated in our department with low-dose splenic irradiation. All patients had either failed more conventional treatment modalities or possessed some contraindication to them. Results: Nine of 10 patients had at least a small, transient rise in their platelet counts, but only two received a substantial therapeutic benefit. Of these two, one died shortly after completing his course of radiation therapy while the other maintained near normal platelet counts up to approximately 3((1)/(2)) years following treatment. There were no treatment-related morbidities and one patient was treated twice. Conclusion: While most patients with HIV-associated ITP may initially respond favorably to splenic irradiation with small rises in platelet count, few responses are likely to be sustained or provide clinically significant outcomes. Our results support those previously reported by others treating this same condition. What remains to be investigated is whether there are any prognostic indicators to help identify those patients most likely to respond to this treatment, thus enabling us to reserve splenic irradiation for those who might derive a substantial benefit from it

  13. Late HIV Diagnosis: Proposed Common Definitions and Associations With Short-Term Mortality.

    Science.gov (United States)

    Jiang, Hongbo; Xie, Nianhua; Liu, Jianhua; Zhang, Zhixia; Liu, Li; Yao, Zhongzhao; Wang, Xia; Nie, Shaofa

    2015-09-01

    The aim of this study was to present a definition of late presentation according to different time periods between initial diagnosis of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) diagnosis which would reliably identify individuals with high risk of mortality within 1 year of diagnosis, and could be used as a suggested common definition.Data of individuals diagnosed from 1994 to February 2012 in Wuhan, China were extracted retrospectively from the national HIV surveillance system. Four time periods (1, 3, 6, and 12 months) combined with the European consensus definition of advanced HIV disease (AHD) were compared. The predictive ability of each definition for identifying an individual who died within 1 year after HIV diagnosis was assessed.A total of 980 patients were included, of whom 289 (29.49%), 324 (33.06%), 353 (36.02%), and 387 (39.49%) were defined as AHD according to the definition of a CD4 count AIDS-defining event (ADE) within 1, 3, 6, and 12 months of HIV diagnosis, respectively. One hundred twenty-seven (12.96%) patients died within 1 year of diagnosis. The highest Youden's index and largest area under the curve were presented in time period within 3 months. Time period within 1 month presented the highest consistency rate, positive likelihood ratio, and kappa value. Longer time periods increased the sensitivity but decreased the specificity.Given the European consensus definitions and the current results, we suggested that AHD could be defined as "a first-reported CD4 count <200 cells/μL or an ADE within 1 month after HIV diagnosis." "Late presentation" could be defined as "a first-reported CD4 count <350 cells/μL or an ADE within 1 month after HIV diagnosis."

  14. Genome-wide association studies on HIV susceptibility, pathogenesis and pharmacogenomics

    NARCIS (Netherlands)

    van Manen, Daniëlle; van 't Wout, Angélique B.; Schuitemaker, Hanneke

    2012-01-01

    Susceptibility to HIV-1 and the clinical course after infection show a substantial heterogeneity between individuals. Part of this variability can be attributed to host genetic variation. Initial candidate gene studies have revealed interesting host factors that influence HIV infection, replication

  15. Lignosulfonic acid exhibits broadly anti-HIV-1 activity--potential as a microbicide candidate for the prevention of HIV-1 sexual transmission.

    Directory of Open Access Journals (Sweden)

    Min Qiu

    Full Text Available Some secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV, herpes simplex virus (HSV, Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA, a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-κB activation and has no significant up-regulation of IL-1α/β and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide.

  16. Role of Prophylactic Oxytocin in the Third Stage of Labor: Physiologic Versus Pharmacologically Influenced Labor and Birth.

    Science.gov (United States)

    Erickson, Elise N; Lee, Christopher S; Emeis, Cathy L

    2017-07-01

    Maternity care providers administer oxytocin prophylactically to prevent postpartum hemorrhage (PPH). Prophylactic oxytocin is generally considered effective and safe and is promoted by national organizations for standardized use. In this article, the evidence supporting prophylactic oxytocin administration for women undergoing spontaneous labor and birth compared with women whose labors included administration of exogenous oxytocin for induction or augmentation is explored. Using data from randomized controlled trials included in 2 recent Cochrane meta-analyses papers, only studies with women in spontaneous labor were selected for inclusion (N = 4 studies). Outcomes of immediate postpartum bleeding volumes (≥ 500 mL or 1000 mL), risk for blood transfusion, and risk for administration of more uterotonic medication were pooled from these 4 studies. Focused random effects meta-analytics were used. Compared to women without prophylactic oxytocin, women who received prophylactic oxytocin had a lower risk of having a 500 mL or higher blood loss. However, prophylactic oxytocin did not lower risk of PPH (≥ 1000 mL), blood transfusion, or need for additional uterotonic treatment. Prophylactic oxytocin may not confer the same benefits to women undergoing spontaneous labor and birth compared to women laboring with oxytocin infusion. Reasons for this difference are explored from a pharmacologic perspective. In addition, the value of prophylactic oxytocin given recent changes in the definition of PPH from greater than or equal to 500 mL to 1000 mL or more after birth is discussed. Finally, gaps in research on adverse effects of prophylactic oxytocin are presented. More research is needed on reducing risk of PPH for women in spontaneous labor. © 2017 by the American College of Nurse-Midwives.

  17. Prophylactic immunoglobulin therapy in secondary immune deficiency

    DEFF Research Database (Denmark)

    Agostini, Carlo; Blau, Igor-Wolfgang; Kimby, Eva

    2016-01-01

    RT in secondary immune deficiencies (SID), and most published guidelines are mere extrapolations from the experience in PID. AREAS COVERED: In this article, four European experts provide their consolidated opinion on open questions surrounding the prophylactic use of IgRT in SID, based on their clinical...

  18. Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage.

    Science.gov (United States)

    Westhoff, Gina; Cotter, Amanda M; Tolosa, Jorge E

    2013-10-30

    Active management of the third stage of labour has been shown to reduce the risk of postpartum haemorrhage (PPH) greater than 1000 mL. One aspect of the active management protocol is the administration of prophylactic uterotonics, however, the type of uterotonic, dose, and route of administration vary across the globe and may have an impact on maternal outcomes. To determine the effectiveness of prophylactic oxytocin at any dose to prevent PPH and other adverse maternal outcomes related to the third stage of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013). Randomised or quasi-randomised controlled trials including pregnant women anticipating a vaginal delivery where prophylactic oxytocin was given during management of the third stage of labour. The primary outcomes were blood loss > 500 mL and the use of therapeutic uterotonics. Two review authors independently assessed trials for inclusion, assessed trial quality and extracted data. Data were checked for accuracy. This updated review included 20 trials (involving 10,806 women). Prophylactic oxytocin versus placebo Prophylactic oxytocin compared with placebo reduced the risk of PPH greater than 500 mL, (risk ratio (RR) 0.53; 95% confidence interval (CI) 0.38 to 0.74; six trials, 4203 women; T² = 0.11, I² = 78%) and the need for therapeutic uterotonics (RR 0.56; 95% CI 0.36 to 0.87, four trials, 3174 women; T² = 0.10, I² = 58%). The benefit of prophylactic oxytocin to prevent PPH greater than 500 mL was seen in all subgroups. Decreased use of therapeutic uterotonics was only seen in the following subgroups: randomised trials with low risk of bias (RR 0.58; 95% CI 0.36 to 0.92; three trials, 3122 women; T² = 0.11, I² = 69%); trials that performed active management of the third stage (RR 0.39; 95% CI 0.26 to 0.58; one trial, 1901 women; heterogeneity not applicable); trials that delivered oxytocin as an IV bolus (RR 0.57; 95% CI 0.39 to 0.82; one trial, 1000 women

  19. Liquefaction of Semen Generates and Later Degrades a Conserved Semenogelin Peptide That Enhances HIV Infection

    Science.gov (United States)

    Liu, Haichuan; Usmani, Shariq M.; Neidleman, Jason; Müller, Janis A.; Avila-Herrera, Aram; Gawanbacht, Ali; Zirafi, Onofrio; Chu, Simon; Dong, Ming; Kumar, Senthil T.; Smith, James F.; Pollard, Katherine S.; Fändrich, Marcus; Kirchhoff, Frank; Münch, Jan; Witkowska, H. Ewa; Greene, Warner C.

    2014-01-01

    ABSTRACT Semen enhances HIV infection in vitro, but how long it retains this activity has not been carefully examined. Immediately postejaculation, semen exists as a semisolid coagulum, which then converts to a more liquid form in a process termed liquefaction. We demonstrate that early during liquefaction, semen exhibits maximal HIV-enhancing activity that gradually declines upon further incubation. The decline in HIV-enhancing activity parallels the degradation of peptide fragments derived from the semenogelins (SEMs), the major components of the coagulum that are cleaved in a site-specific and progressive manner upon initiation of liquefaction. Because amyloid fibrils generated from SEM fragments were recently demonstrated to enhance HIV infection, we set out to determine whether any of the liquefaction-generated SEM fragments associate with the presence of HIV-enhancing activity. We identify SEM1 from amino acids 86 to 107 [SEM1(86-107)] to be a short, cationic, amyloidogenic SEM peptide that is generated early in the process of liquefaction but that, conversely, is lost during prolonged liquefaction due to the activity of serine proteases. Synthetic SEM1(86-107) amyloids directly bind HIV-1 virions and are sufficient to enhance HIV infection of permissive cells. Furthermore, endogenous seminal levels of SEM1(86-107) correlate with donor-dependent variations in viral enhancement activity, and antibodies generated against SEM1(86-107) recognize endogenous amyloids in human semen. The amyloidogenic potential of SEM1(86-107) and its virus-enhancing properties are conserved among great apes, suggesting an evolutionarily conserved function. These studies identify SEM1(86-107) to be a key, HIV-enhancing amyloid species in human semen and underscore the dynamic nature of semen's HIV-enhancing activity. IMPORTANCE Semen, the most common vehicle for HIV transmission, enhances HIV infection in vitro, but how long it retains this activity has not been investigated. Semen

  20. Prophylactic antibiotics in transurethral prostatectomy

    DEFF Research Database (Denmark)

    Qvist, N; Christiansen, H.M.; Ehlers, D

    1984-01-01

    The study included 88 patients with sterile urine prior to transurethral prostatectomy. Forty-five received a preoperative dose of 2 g of cefotaxime (Claforan) and the remaining 43 were given 10 ml of 0.9% NaCl. The two groups did not differ in frequency of postoperative urinary infection (greate...... of infection and the few side effects of the infections that did occur, prophylactic treatment with an antibiotic is not indicated for transurethral prostatectomy in patients with sterile urine....

  1. Newer Gene Editing Technologies toward HIV Gene Therapy

    Directory of Open Access Journals (Sweden)

    Premlata Shankar

    2013-11-01

    Full Text Available Despite the great success of highly active antiretroviral therapy (HAART in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy.

  2. Comparison of preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Guckenberger, M.; Saur, G.; Wehner, D.; Sweeney, R.A.; Flentje, M.; Thalheimer, A.; Germer, C.T.

    2012-01-01

    Background: The purpose of this work was to perform a single institution comparison between preoperative short-course radiotherapy (SC-RT) and long-course radiochemotherapy (LC-RCHT) for locally advanced rectal cancer. Methods: A total of 225 patients with clinical stage UICC II-III rectal cancer were treated with SC-RT (29 Gy in 10 twice daily fractions followed by immediate surgery; n = 108) or LC-RCHT (54 Gy in 28 fractions with simultaneous 5-fluorouracil (5-FU) ± oxaliplatin chemotherapy followed by delayed surgery; n = 117). All patients in the LC-RCHT cohort and patients in the SC-RT with pathological UICC stage ≥ II received adjuvant chemotherapy. Before 2004, the standard of care was SC-RT with LC-RCHT reserved for patients where downstaging was considered as required for sphincter preservation or curative resection. In the later period, SC-RT was practiced only for patients unfit for radiochemotherapy. Results: Patients in the LC-RCHT cohort had a significantly higher proportion of cT4 tumors, clinical node positivity, and lower tumor location. The 5-year local control (LC) and overall survival (OS) were 91% and 66% without differences between the SC-RT and LC-RCHT groups. Acute toxicity was increased during LC-RCHT (grade ≥ II 1% vs. 33%) and there were no differences in postoperative complications. Severe late toxicity grade ≥ III was increased after SC-RT (12% vs. 3%). Of patients aged > 80 years, 7 of 7 patients and 4 of 9 patients received curative surgery after SC-RT and LC-RCHT, respectively. Conclusion: Despite the fact that patients with worse prognostic factors were treated with LC-RCHT, there were no significant differences in LC and OS between the SC-RT and LC-RCHT group. Age > 80 years was identified as a significant risk factor for LC-RCHT and these patients could be treated preferably with SC-RT. (orig.)

  3. Validation of a self-reported HIV symptoms list: the ISS-HIV symptoms scale.

    Science.gov (United States)

    Bucciardini, Raffaella; Pugliese, Katherina; Francisci, Daniela; Costantini, Andrea; Schiaroli, Elisabetta; Cognigni, Miriam; Tontini, Chiara; Lucattini, Stefano; Fucili, Luca; Di Gregorio, Massimiliano; Mirra, Marco; Fragola, Vincenzo; Pompili, Sara; Murri, Rita; Vella, Stefano

    2016-01-01

    To describe the development and the psychometric properties of the Istituto Superiore di Sanità-HIV symptoms scale (lSS-HIV symptoms scale). The ISS-HIV symptom scale was developed by an Italian working team including researchers, physicians and people living with HIV. The development process went through the following steps: (1) review of HIV/AIDS literature; (2) focus group; (3) pre-test analysis; (4) scale validation. The 22 symptoms of HIV-ISS symptoms scale were clustered in five factors: pain/general discomfort (7 items); depression/anxiety (4 items); emotional reaction/psychological distress (5 items); gastrointestinal discomfort (4 items); sexual discomfort (2 items). The internal consistence reliability was for all factors within the minimum accepted standard of 0.70. The results of this study provide a preliminary evidence of the reliability and validity of the ISS-HIV symptoms scale. In the new era where HIV infection has been transformed into a chronic diseases and patients are experiencing a complex range of symptoms, the ISS-HIV symptoms scale may represent an useful tool for a comprehensive symptom assessment with the advantage of being easy to fill out by patients and potentially attractive to physicians mainly because it is easy to understand and requires short time to interpret the results.

  4. Prophylactic effect of a therapeutic vaccine against TB based on fragments of Mycobacterium tuberculosis.

    Science.gov (United States)

    Vilaplana, Cristina; Gil, Olga; Cáceres, Neus; Pinto, Sergio; Díaz, Jorge; Cardona, Pere-Joan

    2011-01-01

    The prophylactic capacity of the RUTI® vaccine, based on fragmented cells of Mycobacterium tuberculosis, has been evaluated in respect to aerosol challenge with virulent bacilli. Subcutaneous vaccination significantly reduced viable bacterial counts in both lungs and spleens of C57Bl mice, when challenged 4 weeks after vaccination. RUTI® protected the spleen less than BCG. Following a 9 month vaccination-challenge interval, protection was observed for the lungs, but not for the spleen. Survival of infected guinea pigs was prolonged by vaccination given 5 weeks before challenge. Inoculations of RUTI® shortly after infection significantly reduced the viable bacterial counts in the lungs, when compared with infected control mice. Thus, vaccination by RUTI® has potential for both the prophylaxis and immunotherapy of tuberculosis.

  5. [Cardiovascular effects produced by prophylactic digitalization during introduction of anaesthesia (author's transl)].

    Science.gov (United States)

    Köppen, R; Köhne, K; Busse, J; Hosselmann, I; Klaschik, E; Simons, F

    1978-10-01

    The narrow field of non-controversial indications concerning the application of digitalis glycosides is pointed out. Problems of routine digitalization of older patients not suffering from cardiac insuffiency are discussed with special regard to preparing them for operations. Up to now, from the viewpoint of anaesthesiologists no benefits of prophylactic digitalization have been found. In a retrospective computerized study, clinical hemodynamic parameters during introduction of anaesthesia have been investigated by means of anaesthetic data recorded during three years. Nondigitalized patients older than fifty years showed satisfactory cardiac functions, whereas prophylactically digitalized patients--compared with the control group--have been treated with plasma expanders earlier and at a double rate. Furthermore, higher heart frequencies and greater tendency to arrythmias were observed. Consequently, prophylactic digitalization cannot be recommended in general.

  6. Prophylactic knee bracing alters lower-limb muscle forces during a double-leg drop landing.

    Science.gov (United States)

    Ewing, Katie A; Fernandez, Justin W; Begg, Rezaul K; Galea, Mary P; Lee, Peter V S

    2016-10-03

    Anterior cruciate ligament (ACL) injury can be a painful, debilitating and costly consequence of participating in sporting activities. Prophylactic knee bracing aims to reduce the number and severity of ACL injury, which commonly occurs during landing maneuvers and is more prevalent in female athletes, but a consensus on the effectiveness of prophylactic knee braces has not been established. The lower-limb muscles are believed to play an important role in stabilizing the knee joint. The purpose of this study was to investigate the changes in lower-limb muscle function with prophylactic knee bracing in male and female athletes during landing. Fifteen recreational athletes performed double-leg drop landing tasks from 0.30m and 0.60m with and without a prophylactic knee brace. Motion analysis data were used to create subject-specific musculoskeletal models in OpenSim. Static optimization was performed to calculate the lower-limb muscle forces. A linear mixed model determined that the hamstrings and vasti muscles produced significantly greater flexion and extension torques, respectively, and greater peak muscle forces with bracing. No differences in the timings of peak muscle forces were observed. These findings suggest that prophylactic knee bracing may help to provide stability to the knee joint by increasing the active stiffness of the hamstrings and vasti muscles later in the landing phase rather than by altering the timing of muscle forces. Further studies are necessary to quantify whether prophylactic knee bracing can reduce the load placed on the ACL during intense dynamic movements. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Easy and accurate reconstruction of whole HIV genomes from short-read sequence data with shiver

    Science.gov (United States)

    Blanquart, François; Golubchik, Tanya; Gall, Astrid; Bakker, Margreet; Bezemer, Daniela; Croucher, Nicholas J; Hall, Matthew; Hillebregt, Mariska; Ratmann, Oliver; Albert, Jan; Bannert, Norbert; Fellay, Jacques; Fransen, Katrien; Gourlay, Annabelle; Grabowski, M Kate; Gunsenheimer-Bartmeyer, Barbara; Günthard, Huldrych F; Kivelä, Pia; Kouyos, Roger; Laeyendecker, Oliver; Liitsola, Kirsi; Meyer, Laurence; Porter, Kholoud; Ristola, Matti; van Sighem, Ard; Cornelissen, Marion; Kellam, Paul; Reiss, Peter

    2018-01-01

    Abstract Studying the evolution of viruses and their molecular epidemiology relies on accurate viral sequence data, so that small differences between similar viruses can be meaningfully interpreted. Despite its higher throughput and more detailed minority variant data, next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of large between- and within-host diversity, including frequent indels, may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to biased loss of information; this bias can distort epidemiological and evolutionary conclusions. De novo assembly avoids this bias by aligning the reads to themselves, producing a set of sequences called contigs. However contigs provide only a partial summary of the reads, misassembly may result in their having an incorrect structure, and no information is available at parts of the genome where contigs could not be assembled. To address these problems we developed the tool shiver to pre-process reads for quality and contamination, then map them to a reference tailored to the sample using corrected contigs supplemented with the user’s choice of existing reference sequences. Run with two commands per sample, it can easily be used for large heterogeneous data sets. We used shiver to reconstruct the consensus sequence and minority variant information from paired-end short-read whole-genome data produced with the Illumina platform, for sixty-five existing publicly available samples and fifty new samples. We show the systematic superiority of mapping to shiver’s constructed reference compared with mapping the same reads to the closest of 3,249 real references: median values of 13 bases called differently and more accurately, 0 bases called differently and less accurately, and 205 bases of missing sequence recovered. We also

  8. The current status of prophylactic replacement therapy in children and adults with haemophilia.

    Science.gov (United States)

    Ljung, Rolf; Gretenkort Andersson, Nadine

    2015-06-01

    Initiating prophylactic treatment at an early age is considered to be the optimal form of therapy for a child with haemophilia A or B. The pioneering long term experiences of prophylactic treatment from Sweden and The Netherlands demonstrated the benefit of prophylaxis in retrospective and observational studies. Decades later, these benefits were confirmed in a randomized controlled study in USA. We review the current status of prophylactic replacement therapy of haemophilia in children, adolescents, adults and the elderly. Prophylaxis should begin at an early age and there are arguments for continuing it into adulthood. The dose of prophylaxis is dependent on the goal of treatment, economic resources and venous access and should be tailored individually. Starting the first exposures to clotting factor concentrates as prophylactic treatment, instead of on-demand in response to a bleed, may decrease the frequency of inhibitors in patients with haemophilia A. Novel longer-acting products are being introduced that could be helpful for patients with difficult venous access and enable higher trough levels. © 2015 John Wiley & Sons Ltd.

  9. «Short Course in History of Ukraine» in the Context of Soviet Scientific History of late 1940s

    Directory of Open Access Journals (Sweden)

    Lubov A. Sidorova

    2012-06-01

    Full Text Available The contribution considers one of the events of ideological campaign, struggling for cosmopolitism, bourgeois objectivism and nationalism in Soviet historical science of the late 1940s. Special attention is attached to the consideration of the model “Short Course in History of Ukraine” as the instrument of political and ideological verification.

  10. The EC randomised controlled trial of prophylactic ethamsylate for very preterm neonates: early mortality and morbidity. The EC Ethamsylate Trial Group.

    OpenAIRE

    1994-01-01

    Immature infants are at increased risk of death and disability, often related to haemorrhagic and ischaemic brain damage. Two controlled trials have suggested that a policy of prophylactic ethamsylate may reduce this damage. The aim of the trial reported here was to assess the effects of such a policy in respect of death, disability, and the use of health service resources up to 2 years of age. Short term findings are reported here. Three hundred and thirty four immature (< or = 32 weeks' ges...

  11. CERN Technical Training: Places available for forthcoming courses

    CERN Multimedia

    2007-01-01

    The following course sessions are scheduled in the framework of the CERN Technical Training Program 2007 and still have places available. You may find the full, updated Technical Training course program on our web-catalogue web-catalogue. OFFICE SOFTWARE CERN EDMS Introduction E 24.9 1 d Outlook 2007 (Short Course II) - Calendar, Tasks and Notes E/F 28.9 0.5 d Outlook 2007 (Short Course III) - Meeting and Delegation E/F 28.9 0.5 d Excel 2007 Niveau 2 : ECDL F 11-12.10 2 d Excel 2007 (Short Course II) - How to format your worksheet for printing E/F 12.10 0.5 d Excel 2007 (Short Course I) - How to work with Formulae E/F 21.9 1/2 d Nouveauté Word 2007 E/F 22.10 1 d Nouveauté Excel 2007 E/F 23.10 1/2 d Excel 2007 Level 2 : ECDL F 25-26.10 2 d In...

  12. CERN Technical Training: Places available for forthcoming courses

    CERN Multimedia

    2007-01-01

    The following course sessions are scheduled in the framework of the CERN Technical Training Program 2007 and still have places available. You may find the full, updated Technical Training course program on our web-catalogue web-catalogue. OFFICE SOFTWARE Outlook 2007 (Short Course II) - Calendar, Tasks and Notes E/F 28.9 0.5 d Outlook 2007 (Short Course III) - Meeting and Delegation E/F 28.9 0.5 d Excel 2007 Niveau 2 : ECDL F 11-12.10 2 d Excel 2007 (Short Course II) - How to format your worksheet for printing E/F 12.10 0.5 d Excel 2007 (Short Course I) - How to work with Formulae E/F 21.9 1/2 d Nouveauté Word 2007 E/F 22.10 1 d Nouveauté Excel 2007 E/F 23.10 1/2 d Excel 2007 Level 2 : ECDL F 25-26.10 2 d Introduction to Sharepoint E 29.10 1 d ...

  13. Impact of a course on human sexuality and adolescence.

    Science.gov (United States)

    Saksena, Sangeeta; Saldanha, Shaibya

    2003-03-01

    This study was conducted as part of a course on Human Sexuality and Adolescence for school children to ascertain the prior knowledge of children, source of their knowledge and whether the course was a felt need of the children. Students were given a questionnaire before the course. Few selected questions were asked again after the last session. The course was conducted in a private co-educational English medium school in urban Bangalore involving 392 students 13-15 years of age. The course was designed by the authors and dealt with anatomy, physiology, social and psychological aspects of growing up, HIV and contraception. 55-70% of class VIII, IX and X students had learnt about sex from friends, 30% from movies, 15% from text books and only 10% from parents. Misconceptions about anatomy, childbirth, HIV were common. 90% of tenth class students felt that education in human sexuality was necessary. In spite of chapters on reproduction in textbooks, children turn to peers or media to gather information on sexuality. Education in human sexuality is required in our schools, as this need is currently not being addressed adequately in our society.

  14. Health & nutritional status of HIV infected children in Hyderabad, India.

    Science.gov (United States)

    Swetha, G Krishna; Hemalatha, R; Prasad, U V; Murali, Vasudev; Damayanti, K; Bhaskar, V

    2015-01-01

    Information on nutritional status of HIV infected children from India is lacking and is required before taking up nutritional supplementation trials. Thus, the aim of the present study was to assess the growth and morbidity status of HIV infected children over a period of one year in a city in southern India. This was an observational study carried out between July 2009 and February 2011, at two orphanages in Hyderabad, India. Seventy seven HIV-positive children aged between 1 and half and 15 years, both on and not on antiretroviral therapy (ART) were included. Nutritional status was assessed longitudinally for one year by weight gain, linear growth and body composition. Serum samples were analyzed for haemoglobin, micronutrients, CD4 and CD8 counts. Dietary intakes were assessed by institutional diet survey and morbidity data were recorded every day for 12 months. Mean energy intakes were less than recommended dietary allowance (RDA) in all age groups. Iron and folate intakes were less than 50 per cent of RDA; 46 (59.7%) children were stunted, 36 (46.8%) were underweight and 15 (19.5%) had low BMI for age. Anaemia was observed in 35 (45.5%) children. Micronutrient deficiencies such as vitamin D (40/77; 51.9%), vitamin A (11/77; 14.3%), folate (37/77; 48.1%), iron (38/77; 49.3%) were widely prevalent. HIV viral load was higher in children not on ART and those with morbidity. Respiratory (36.6%) and dermatological illnesses (18.8%) were the commonest presentations. Acute, chronic malnutrition and micronutrient deficiencies were common in HIV infected children, especially in those not on ART and having morbidity. With severe malnutrition being an alarming consequence of HIV, prophylactic nutritive care should be considered for integration into HIV care strategies besides initiation of ART to improve the nutritional status and quality of life of these children.

  15. CERN Technical Training: available Places in forthcoming Courses

    CERN Multimedia

    HR Department

    2009-01-01

    The following course sessions are scheduled in the framework of the 2008 CERN Technical Training Programme and places are still available. You can find the full updated Technical Training course programme in our web catalogue (http://cta.cern.ch/cta2/f?p=110:9). OFFICE SOFTWARE Word 2007 – Level 2 : ECDL\t(English)\t04-05.05\t2 days Excel 2007 – Level 2 : ECDL\t(English)\t07-08.05\t2 days Novelties Office 2007 : Word 2007\t(Français)\t11.05\t1 jour Secure e-mail and Web browsing\t(Français)\t19.05\t1.5 heure Outlook 2007 (Short Course 1) – E-mail\t(Bilingual)\t25.05\t3 hours Outlook 2007 (Short Course II) – Calendar, Tasks and Notes (Bilingual)\t25.05\t3 hours Outlook 2007 (Short Course III) – Meetings and Delegation (Bilingual)\t26.05\t3 hours Outlook 2007 (Short Course II) – HowTo…Mail merge (with Outlook)\t(Bilingual)\t26.05\t3 hours Word 2007 (Short Course III) - Working with long documents: Styles and tables of content\t(Bilingual)\t28.05\t3 hours Indico – Meeting Organization\t(English)\t05.06\t2 hours Indico ...

  16. Science ethics education part II: changes in attitude toward scientific fraud among medical researchers after a short course in science ethics.

    Science.gov (United States)

    Vuckovic-Dekic, L; Gavrilovic, D; Kezic, I; Bogdanovic, G; Brkic, S

    2012-01-01

    To determine the impact of the short science ethics courses on the knowledge of basic principles of responsible conduct of research (RCR), and on the attitude toward scientific fraud among young biomedical researchers. A total of 361 attendees of the course on science ethics answered a specially designed anonymous multiple- choice questionnaire before and after a one-day course in science ethics. The educational course consisted of 10 lectures: 1) Good scientific practice - basic principles; 2) Publication ethics; 3) Scientific fraud - fabrication, falsification, plagiarism; 4) Conflict of interests; 5) Underpublishing; 6) Mentorship; 7) Authorship; 8) Coauthorship; 9) False authorship; 10) Good scientific practice - ethical codex of science. In comparison to their answers before the course, a significantly higher (pscience ethics as sufficient after the course was completed. That the wrongdoers deserve severe punishment for all types of scientific fraud, including false authorship, thought significantly (pscience ethics had a great impact on the attendees, enlarging their knowledge of responsible conduct of research and changing their previous, somewhat opportunistic, behavior regarding the reluctance to react publicly and punish the wrongdoers.

  17. CERN Technical Training: available Places in forthcoming Courses

    CERN Multimedia

    2008-01-01

    The following course sessions are scheduled in the framework of the CERN Technical Training Program 2008 and places are still available. You may find the full updated Technical Training course program in our web-catalogue. OFFICE SOFTWARE Sharepoint Collaboration Workspace\tF\t04.02\t1 d Office 2007 – Nouveautés/Novelties\tB\t05.02\t1 d Outlook 2007 (Short course I) – Email\tB\t07.02\t0.5 d Outlook 2007 (Short course II) - Calendar, Tasks, Notes\tB\t07.02\t0.5 d Outlook 2007 (Short course III) Meeting and Delegation\tB\t08.02\t0.5 d Word 2007 (Short course IV) – Master document\tB\t08.02\t0.5 d ACCESS 2007 - level 1 : ECDL\tE\t13-14.02\t2 d Sharepoint Collaboration Workspace\tE\t25.02\t1 d Word – Level 1\tE\t25-26.02\t2 d Excel – Level 1\tE\t28-29.02\t2 d Office 2007 –Novelties\tE\t03.03\t1 d Sharepoint designer (Frontpage) – Level 1\tE\t05-06.03\t2 d Word 2007 (Short course I: HowTo. work with AutoTasks)\tB\t31.03\t0.5 d Word 2007 (Short course II: HowTo mail merge)\tB\t31.03\t0.5 d SOFTWARE AND SYS...

  18. [Travel medicine for HIV-infected patients].

    Science.gov (United States)

    Rossi, M; Furrer, H

    2001-06-01

    Many HIV-infected persons travel from temperate zones to (sub)tropical destinations. HIV-specific immigration issues, medical resources abroad and problems regarding travelling with multiple medications have to be anticipated. When prescribing immunizations and specific chemoprophylaxis, the stage of immunodeficiency as well as drug interactions with antiretrovirals and medicaments against opportunistic infections have to be taken into account. Live vaccines may be contraindicated. Immunocompromised HIV-infected travellers have a higher risk for serious courses of diseases by enteropathogens. Therefore a good information about food hygiene is important and a prescription of an antibiotic to take in case of severe diarrhea may be indicated. A new antiretroviral combination therapy should not be started immediately before travelling to the tropics. The possibility to continue an established HIV treatment during travel has to be evaluated cautiously. With good pre-travel advice the risk of severe health problems is low for most HIV-infected travellers.

  19. Improving outcomes in infants of HIV-infected women in a developing country setting.

    Science.gov (United States)

    Noel, Francine; Mehta, Sapna; Zhu, Yuwei; Rouzier, Patricia De Matteis; Marcelin, Abdias; Shi, Jian R; Nolte, Claudine; Severe, Linda; Deschamps, Marie Marcelle; Fitzgerald, Daniel W; Johnson, Warren D; Wright, Peter F; Pape, Jean W

    2008-01-01

    Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries. We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given "short-course" monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08-0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16-0.30], Pbirth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis. Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant.

  20. Is prophylactic fixation a cost-effective method to prevent a future contralateral fragility hip fracture?

    Science.gov (United States)

    Faucett, Scott C; Genuario, James W; Tosteson, Anna N A; Koval, Kenneth J

    2010-02-01

    : A previous hip fracture more than doubles the risk of a contralateral hip fracture. Pharmacologic and environmental interventions to prevent hip fracture have documented poor compliance. The purpose of this study was to examine the cost-effectiveness of prophylactic fixation of the uninjured hip to prevent contralateral hip fracture. : A Markov state-transition model was used to evaluate the cost and quality-adjusted life-years (QALYs) for unilateral fixation of hip fracture alone (including internal fixation or arthroplasty) compared with unilateral fixation and contralateral prophylactic hip fixation performed at the time of hip fracture or unilateral fixation and bilateral hip pad protection. Prophylactic fixation involved placement of a cephalomedullary nail in the uninjured hip and was initially assumed to have a relative risk of a contralateral fracture of 1%. Health states included good health, surgery-related complications requiring a second operation (infection, osteonecrosis, nonunion, and malunion), fracture of the uninjured hip, and death. The primary outcome measure was the incremental cost-effectiveness ratio estimated as cost per QALY gained in 2006 US dollars with incremental cost-effectiveness ratios below $50,000 per QALY gained considered cost-effective. Sensitivity analyses evaluated the impact of patient age, annual mortality and complication rates, intervention effectiveness, utilities, and costs on the value of prophylactic fixation. : In the baseline analysis, in a 79-year-old woman, prophylactic fixation was not found to be cost-effective (incremental cost-effectiveness ratio = $142,795/QALY). However, prophylactic fixation was found to be a cost-effective method to prevent contralateral hip fracture in: 1) women 71 to 75 years old who had 30% greater relative risk for a contralateral fracture; and 2) women younger than age 70 years. Cost-effectiveness was greater when the additional costs of prophylaxis were less than $6000. However, for

  1. The effect of prophylactic knee bracing on proprioception ...

    African Journals Online (AJOL)

    Enrique

    S Davies (BA Hons, MA Ergonomics, PhD). Department of Human ... of joint position in space as sensed by the central nervous system.23. It incorporates joint .... The finding of this work supports the research hypothesis that prophylactic knee ...

  2. A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection

    NARCIS (Netherlands)

    Dybul, M; Nies-Kraske, E; Dewar, R; Maldarelli, F; Hallahan, CW; Daucher, M; Piscitelli, SC; Ehler, L; Weigand, A; Palmer, S; Metcalf, JA; Davey, RT; Kress, DMR; Powers, A; Beck, [No Value; Frenkel, L; Baseler, M; Coffin, J; Fauci, AS

    2004-01-01

    Background. We previously demonstrated that short-cycle structured intermittent therapy ( SIT; 7 days without therapy followed by 7 days with antiretroviral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppression of plasma HIV viremia while reducing serum

  3. A Modified Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers

    Science.gov (United States)

    2013-10-01

    Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers Authors: DISTRIBUTION STATEMENT A. Paul C. Algra, LT, MC...May 2012 – May 2013 4. TITLE AND SUBTITLE A Modified Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers...SUPPLEMENTARY NOTES 14. ABSTRACT To prevent acute otitis externa (AOE) in the saturation setting and to decrease the side effects

  4. BI-2 destabilizes HIV-1 cores during infection and Prevents Binding of CPSF6 to the HIV-1 Capsid.

    Science.gov (United States)

    Fricke, Thomas; Buffone, Cindy; Opp, Silvana; Valle-Casuso, Jose; Diaz-Griffero, Felipe

    2014-12-11

    The recently discovered small-molecule BI-2 potently blocks HIV-1 infection. BI-2 binds to the N-terminal domain of HIV-1 capsid. BI-2 utilizes the same capsid pocket used by the small molecule PF74. Although both drugs bind to the same pocket, it has been proposed that BI-2 uses a different mechanism to block HIV-1 infection when compared to PF74. This work demonstrates that BI-2 destabilizes the HIV-1 core during infection, and prevents the binding of the cellular factor CPSF6 to the HIV-1 core. Overall this short-form paper suggests that BI-2 is using a similar mechanism to the one used by PF74 to block HIV-1 infection.

  5. Present and future of prophylactic antibiotics for severe acute pancreatitis

    Science.gov (United States)

    Jiang, Kun; Huang, Wei; Yang, Xiao-Nan; Xia, Qing

    2012-01-01

    AIM: To investigate the role of prophylactic antibiotics in the reduction of mortality of severe acute pancreatitis (SAP) patients, which is highly questioned by more and more randomized controlled trials (RCTs) and meta-analyses. METHODS: An updated meta-analysis was performed. RCTs comparing prophylactic antibiotics for SAP with control or placebo were included for meta-analysis. The mortality outcomes were pooled for estimation, and re-pooled estimation was performed by the sensitivity analysis of an ideal large-scale RCT. RESULTS: Currently available 11 RCTs were included. Subgroup analysis showed that there was significant reduction of mortality rate in the period before 2000, while no significant reduction in the period from 2000 [Risk Ratio, (RR) = 1.01, P = 0.98]. Funnel plot indicated that there might be apparent publication bias in the period before 2000. Sensitivity analysis showed that the RR of mortality rate ranged from 0.77 to 1.00 with a relatively narrow confidence interval (P antibiotic prophylaxis. CONCLUSION: Current evidences do not support prophylactic antibiotics as a routine treatment for SAP, but the potentially benefited sub-population requires further investigations. PMID:22294832

  6. Adolescent girls and young women: key populations for HIV epidemic control.

    Science.gov (United States)

    Dellar, Rachael C; Dlamini, Sarah; Karim, Quarraisha Abdool

    2015-01-01

    At the epicentre of the HIV epidemic in southern Africa, adolescent girls and young women aged 15-24 contribute a disproportionate ~30% of all new infections and seroconvert 5-7 years earlier than their male peers. This age-sex disparity in HIV acquisition continues to sustain unprecedentedly high incidence rates, and preventing HIV infection in this age group is a pre-requisite for achieving an AIDS-free generation and attaining epidemic control. Adolescent girls and young women in southern Africa are uniquely vulnerable to HIV and have up to eight times more infection than their male peers. While the cause of this vulnerability has not been fully elucidated, it is compounded by structural, social and biological factors. These factors include but are not limited to: engagement in age-disparate and/or transactional relationships, few years of schooling, experience of food insecurity, experience of gender-based violence, increased genital inflammation, and amplification of effects of transmission co-factors. Despite the large and immediate HIV prevention need of adolescent girls and young women, there is a dearth of evidence-based interventions to reduce their risk. The exclusion of adolescents in biomedical research is a huge barrier. School and community-based education programmes are commonplace in many settings, yet few have been evaluated and none have demonstrated efficacy in preventing HIV infection. Promising data are emerging on prophylactic use of anti-retrovirals and conditional cash transfers for HIV prevention in these populations. There is an urgent need to meet the HIV prevention needs of adolescent girls and young women, particularly those who are unable to negotiate monogamy, condom use and/or male circumcision. Concerted efforts to expand the prevention options available to these young women in terms of the development of novel HIV-specific biomedical, structural and behavioural interventions are urgently needed for epidemic control. In the interim

  7. Serious Non-AIDS Conditions in HIV

    DEFF Research Database (Denmark)

    Lundgren, Jens D; Borges, Alvaro H; Neaton, James D

    2018-01-01

    PURPOSE OF REVIEW: Optimal control of HIV can be achieved by early diagnosis followed by the initiation of antiretroviral therapy (ART). Two large randomised trials (TEMPRANO and START) have recently been published documenting the clinical benefits to HIV-positive adults of early ART initiation....... Main findings are reviewed with a focus on serious non-AIDS (SNA) conditions. RECENT FINDINGS: Data from the two trials demonstrated that initiating ART early in the course of HIV infection resulted in marked reductions in the risk of opportunistic diseases and invasive bacterial infections....... This indicates that HIV causes immune impairment in early infection that is remedied by controlling viral replication. Intriguingly, in START, a marked reduction in risk of cancers, both infection-related and unrelated types of cancers, was observed. Like the findings for opportunistic infections, this anti...

  8. A RANDOMIZED CONTROLLED STUDY OF RISK FACTORS AND ROLE OF PROPHYLACTIC ANTIBIOTICS IN PREVENTION OF SURGICAL SITE INFECTIONS

    Directory of Open Access Journals (Sweden)

    Avijeet Mukherjee, Naveen N

    2015-01-01

    Full Text Available Background and Objectives: Surgical site infection (SSI is the most common nosocomial infection encountered in post operative surgical wards. The use of prophylactic antibiotic in clean elective surgical cases is still a subject of controversy to surgeons. The objective of the study is to identify the need for using prophylactic antibiotics in clean surgeries, prevalence of organisms in patients who are not given prophylactic antibiotics and to study whether the presence of risk factors increase the incidence of surgical site infection. Methodology: The comparative study consists of 100 cases admitted under two groups of 50 each: Group A was given prophylactic antibiotic and Group B didn’t receive any. All surgeries other than clean surgical cases were excluded from the study. Results: Out of 50 patients in group B who were not given prophylactic antibiotic, 2 patients had more than one risk factor for development of SSI and both of them developed SSI. Of the 50 patients who received prophylactic antibiotic, none developed SSI. The rate of infection in group A was nil and in Group B was 4%. Conclusion: Prophylactic antibiotics are not recommended for clean elective surgical cases as there is no statistically significant change in the infection rate seen in patients not receiving prophylactic antibiotic(P=0.4952. Meticulous surgical technique and correcting risk factors prior to surgery is a must for reducing incidence of SSI.

  9. Radiation-induced leukopenia in breast cancer patients receiving prophylactic irradiation, and analysis of the effects of some drugs

    Energy Technology Data Exchange (ETDEWEB)

    Ohkawa, T; Tsuya, A; Kaneda, K [Japanese Foundation for Cancer Research, Tokyo. Hospital

    1975-06-01

    Radiation-induced leukopenia was analyzed and assessed in breast cancer patients receiving prophylactic irradiation after radical mastectomy. Average white blood cell counts decreased to about 67 percent of the initial value after irradiation, and the ratio of the decrease was greater when the initial value was higher. During the course of the irradiation, white blood cell counts decreased to the lowest value by the middle of treatment time and stayed at the same level for one month after irradiation. The restorative or protective effects of taurine and cytochrome C were assessed by an open study, and that of DNA-spermidine by a double blind test, and the significant effects of each was observed.

  10. Efficacy of prophylactic phototherapy for prevention of hyperbilirubinemia in very low birth weight newborns

    Directory of Open Access Journals (Sweden)

    M. A. Mannan

    2016-08-01

    Full Text Available Background: Jaundice is a common clinical condition in newborn occurring in approximately 60% of term and 80% of preterm infants. Unconjugated hyperbilirubinemia is universally common in all preterm infants especially in newborns with very low biLth weight. Low birth weight and premature infants are at major risk for exaggerated hyperbilirubinemia that can lead to bilirubin encephalopathy. Significant heterogeneity in the approach to the treatment of jaundiced neonates exists throughout the world. Phototherapy is the most common treatment for neonatal hyperbilirubinemia and could be most effective in preventing the sequelae of hyperbilirubinemia if initiated prophylactically. This randomized clinical trial has been proposed with the objective of assessing the efficacy of prophylactic photo therapy in preventing significant rise of unconjugated hyperbilirubinemia in premature neonates weighing less than 1500 gram and therefore to decrease the need for exchange transfusion and finally to reduce hospital stay due to hyperbilirubinemia. Methods: This randomized controlled clinical trial enrolled sixty newborns with birth weight less than 1500 gram. They were divided into two groups: 1 Prophylactic group, in whom phototherapy was started within 24 hours of birth and continued for 7 days and 2 Control group in whom therapeutic phototherapy was started considering serum bilirubin level and other clinical condi­tions as per institutional guidelines. Mean value of total serum bilirubin (TSB, duration of phototherapy, the need for exchange transfusion and duration of hospital stay in both groups were analyzed.Results: The maximum mean TSB level in prophylactic group was observed on 7th day and in control group it was observed on 3rd day of life. The total serum bilirubin levels were significantly lower in the 3rd and 5th days of life in the prophylactic group in comparison to control group (P value 0.001. Total serum bilirubin level exceeded therapeutic

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

    Science.gov (United States)

    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.

  12. Quality of antenatal and delivery care before and after the implementation of a prevention of mother-to-child HIV transmission programme in Côte d'Ivoire.

    Science.gov (United States)

    Delvaux, Thérèse; Konan, Jean-Paul Diby; Aké-Tano, Odile; Gohou-Kouassi, Valérie; Bosso, Patrice Emery; Buvé, Anne; Ronsmans, Carine

    2008-08-01

    To assess whether implementation of a prevention of mother-to-child HIV transmission (PMTCT) programme in Côte d'Ivoire improved the quality of antenatal and delivery care services. Quality of antenatal and delivery care services was assessed in five urban health facilities before (2002-2003) and after (2005) the implementation of a PMTCT programme through review of facility data; observation of antenatal consultations (n = 606 before; n = 591 after) and deliveries (n = 229 before; n = 231 after) and exit interviews of women; and interviews of health facility staff. HIV testing was never proposed at baseline and was proposed to 63% of women at the first ANC visit after PMTCT implementation. The overall testing rate was 42% and 83% of tested HIV-infected pregnant women received nevirapine. In addition, inter-personal communication and confidentiality significantly improved in all health facilities. In the maternity ward, quality of obstetrical care at admission, delivery and post-partum care globally improved in all facilities after the implementation of the programme although some indicators remained poor, such as filling in the partograph directly during labour. Episiotomy rates among primiparous women dropped from 64% to 25% (P implementation. Global scores for quality of antenatal and delivery care significantly improved in all facilities after the implementation of the programme. Introducing comprehensive PMTCT services can improve the quality of antenatal and delivery care in general.

  13. Disease severity, self-reported experience of workplace discrimination and employment loss during the course of chronic HIV disease: differences according to gender and education.

    OpenAIRE

    Dray-Spira , Rosemary; Gueguen , Alice; Lert , France; Study Group , Vespa

    2008-01-01

    International audience; OBJECTIVES: Evidence for the existence of a harmful effect of chronic disease on employment status has been provided. Although this effect of chronic illness on employment has been reported to be higher among the groups with the lowest position on the labour market, the mechanisms of such inequalities are poorly understood. The present study aimed at investigating social inequalities in the chances of maintaining employment during the course