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Context Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL. Intervention Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (−4.8% and −4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, −0.6%; 95% CI, −4.8% to 3.6%; P=.80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (−85 cells/μL vs −23 cells/μL at week 48; difference, −62 cells/μL; 95% CI, −115 to −8; P=.03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P=.003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P=.03). Conclusion Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication. Trial Registration isrctn.org Identifier: ISRCTN30019040

Good adherence with taking prescribed medication was associated with virologic response. Social factors were important in explaining nonadherence.

Objectives: To evaluate the efficacy and cost effectiveness of self applied podophyllotoxin 0.5% solution and podophyllotoxin 0.15% cream, compared to clinic applied 25% podophyllin in the treatment of genital warts over 4 weeks. Methods: We conducted a randomised controlled trial in 358 immunocompetent men and women with genital warts of 3 months' duration or less. Results: In the principal analysis both podophyllotoxin solution (OR 2.93, 95% CI 1.56 to 5.50) and podophyllotoxin cream (OR 1.97, 95% CI 1.04 to 3.70) were associated with significantly increased odds of remission of all warts compared to podophyllin. We performed two further analyses. When subjects defaulting from follow up were assumed to have been cured odds of remission of all warts were also significantly increased both for podophyllotoxin solution (OR 3.04, 95% CI 1.68 to 5.49) and for podophyllotoxin cream (OR 2.46, 95% CI 1.38 to 4.40). When subjects defaulting from follow up were assumed not to have been cured odds of remission of all warts were significantly increased for podophyllotoxin solution (OR 1.92, 95% CI 1.13 to 3.27), but not for podophyllotoxin cream (OR 1.17, 95% CI 0.69 to 2.00). Local side effects were seen in 24% of subjects, and recurrence of warts within 12 weeks of study entry in 43% of all initially cleared subjects, without statistically significant differences between the treatment groups. Direct, indirect, and total costs were similar across the three treatment groups. Podophyllotoxin solution was the most cost effective treatment, followed by podophyllotoxin cream, with podophyllin treatment being the least cost effective. Conclusions: Self treatment of anogenital warts with podophyllotoxin showed greater efficacy and cost effectiveness than clinic based treatment with podophyllin.

BackgroundGlobally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia.Methods and findingsThrough the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitat...

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There was more extensive genotypic resistance in both treatment groups than is generally seen in resource-rich settings. However, significant residual activity was observed among patients with virological failure, particularly those receiving zidovudine-lamivudine plus abacavir.

BackgroundGlobal HIV-1 genetic diversity and evolution form a major challenge to treatment and prevention efforts. An increasing number of distinct HIV-1 recombinants have been identifiedworldwide, but their contribution to the global epidemic is unknown. We aimed to estimate the global and regional distribution of HIV-1 recombinant forms during 1990-2015. MethodsWe assembled a global HIV-1 molecular epidemiology database through a systematic literature review and a global survey. We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published from Jan 1, 1990, to Dec 31, 2015. Unpublished original HIV-1 subtyping data was collected through a survey among experts in the field who were members of the WHO-UNAIDS Network for HIV Isolation and Characterisation. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. Countries were grouped into 14 regions and analyses conducted for four time periods (1990-99, 2000-04, 2005-09 and 2010-15). The distribution of circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV in each country to generate regional and global estimates of numbers and proportions of HIV-1 recombinants in each time period. The systematic review is registered with PROSPERO, number CRD42017067164.