Showing papers by "Myron S. Cohen published in 2016"
TL;DR: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners, and was associated with a 93% lower risk of linked partner infection than was delayed ART.
Abstract: BackgroundAn interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. MethodsWe randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked H...
1,191 citations
TL;DR: It is found that broadly neutralizing antibody production associates with particular immune traits, including a higher frequency of autoantibodies, fewer regulatory T cells, and more circulating memory T follicular helper cells, in HIV-1–infected individuals.
Abstract: Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. bnAbs occur in some HIV-1–infected individuals and frequently have characteristics of autoantibodies. We have studied cohorts of HIV-1–infected individuals who made bnAbs and compared them with those who did not do so, and determined immune traits associated with the ability to produce bnAbs. HIV-1–infected individuals with bnAbs had a higher frequency of blood autoantibodies, a lower frequency of regulatory CD4 + T cells, a higher frequency of circulating memory T follicular helper CD4 + cells, and a higher T regulatory cell level of programmed cell death–1 expression compared with HIV-1–infected individuals without bnAbs. Thus, induction of HIV-1 bnAbs may require vaccination regimens that transiently mimic immunologic perturbations in HIV-1–infected individuals.
96 citations
University of Edinburgh1, University of KwaZulu-Natal2, Imperial College London3, Wellcome Trust Sanger Institute4, University of North Carolina at Chapel Hill5, University College London6, University of Washington7, Johns Hopkins University8, Harvard University9, University College Hospital10, University of London11, Barts Health NHS Trust12
TL;DR: Using longer sequences derived from nearly whole genomes will improve the reliability of phylogenetic reconstruction, particularly when based on short sequences.
Abstract: HIV molecular epidemiology studies analyse viral pol gene sequences due to their availability, but whole genome sequencing allows to use other genes. We aimed to determine what gene(s) provide(s) the best approximation to the real phylogeny by analysing a simulated epidemic (created as part of the PANGEA_HIV project) with a known transmission tree. We sub-sampled a simulated dataset of 4662 sequences into different combinations of genes (gag-pol-env, gag-pol, gag, pol, env and partial pol) and sampling depths (100%, 60%, 20% and 5%), generating 100 replicates for each case. We built maximum-likelihood trees for each combination using RAxML (GTR + Γ), and compared their topologies to the corresponding true tree’s using CompareTree. The accuracy of the trees was significantly proportional to the length of the sequences used, with the gag-pol-env datasets showing the best performance and gag and partial pol sequences showing the worst. The lowest sampling depths (20% and 5%) greatly reduced the accuracy of tree reconstruction and showed high variability among replicates, especially when using the shortest gene datasets. In conclusion, using longer sequences derived from nearly whole genomes will improve the reliability of phylogenetic reconstruction. With low sample coverage, results can be highly variable, particularly when based on short sequences.
25 citations
TL;DR: Observed declines in HIV incidence in Vancouver between 1996 and 2007 should be seen as a success for intensive harm reduction, whereas ART probably played a small role.
Abstract: Background Population-level associations between community measures of HIV viral load and HIV incidence have been interpreted as evidence for HIV anti-retroviral treatment (ART) as prevention among people who inject drugs (PWID). However, investigation of concurrent HCV and HIV incidence trends allows examination of alternative explanations for the fall in HIV incidence. We estimate the contribution of ART and reductions in injecting risk for reducing HIV incidence in Vancouver between 1996 and 2007. Methods A deterministic model of HIV and HCV transmission among PWID was calibrated to the baseline (1996) HIV and HCV epidemic among PWID in Vancouver. While incorporating parameter uncertainty, the model projected what levels of ART protection and decreases in injecting risk could reproduce the observed reduction in HIV and HCV incidence for 1996-2007, and so what impact would have been achieved with just ART or just reductions in injecting risk. Results Model predictions suggest the estimated reduction (84%) in HCV incidence for 1996-2007 required a 59% (2.5-97.5 percentile range 49-76%) reduction in injecting risk, which accounted for nine-tenths of the observed decrease in HIV incidence; the remainder was achieved with a moderate ART efficacy for reducing sexual HIV infectivity (70%, 51-89%) and an uncertain ART efficacy for reducing injection-related HIV infectivity (44%, 0-96%). Despite this uncertainty, projections suggest that the decrease in injecting risk reduced HIV incidence by 76% (63-85%) and ART further reduced HIV incidence by 8% (2-19%), or on its own by 3% (-34-37%). Conclusions Observed declines in HIV incidence in Vancouver between 1996 and 2007 should be seen as a success for intensive harm reduction, whereas ART probably played a small role.
24 citations
Johns Hopkins University School of Medicine1, Fred Hutchinson Cancer Research Center2, Bhabha Atomic Research Centre3, University of North Carolina at Chapel Hill4, Johns Hopkins University5, Harvard University6, Chiang Mai University7, University of Zimbabwe8, University of the Witwatersrand9, Kenya Medical Research Institute10, Indian Council of Medical Research11, Oswaldo Cruz Foundation12, Fenway Health13
TL;DR: Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits and high baseline viral load and less education were associated with emergence of resistance at ART failure.
Abstract: Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.
15 citations
TL;DR: Enhanced PN services may be feasible among MSM in South China and Internet and mobile phone PN may contact partners untraceable by traditional PN.
Abstract: Background
Syphilis is prevalent among men who have sex with men (MSM) in China. Syphilis partner notification (PN) programs targeting MSM has been considered as one of effective strategies to prevention and control of the infection in the population. We examined willingness and preferences for PN among MSM to measure feasibility and optimize uptake.
8 citations
2 citations
TL;DR: High patient loads at HIV clinics was strongly associated with increased risk of HIV transmission in the population, particularly at village-level clinics, and increased travel distance had divergent effects based on clinic tier, suggesting unique mechanisms operating across levels of resource availability.
1 citations
TL;DR: The model shines a light on three crucial ingredients for success of the NHAS that are not really independent of one another: retention in HIV care, the cost of the health-care infrastructure for retention in care, and the potential extreme costs of ART.