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Treatment as long-term prevention: sustained reduction in HIV sexual transmission risk with use of antiretroviral therapy in rural Uganda.

ABSTRACT: Suppressive antiretroviral therapy (ART) substantially decreases HIV transmission in clinical research settings. We sought to measure the frequency and correlates of periods of transmission risk among individuals taking ART during multiple years of observation in rural, southwestern Uganda.Observational cohort study.We collected sexual behavior and viral load data in a Ugandan cohort of people living with HIV/AIDS from the time of ART initiation. We defined each 90-day visit as a potential transmission period if HIV-1 RNA was more than 400?copies/ml and the participant reported sexual transmission risk behavior, defined as unprotected sexual contact with at least 1 HIV-uninfected partners or partners of unknown serostatus in the prior 90 days.We evaluated data from 463 individuals on ART over a median 3.5 years of observation and 5293 total study visits. During that time, over half (259, 56%) had detectable viremia or reported sexual transmission risk behavior at least once. However, only 23 (5%) had both simultaneously, at 28 (<1%) of all visits. Transmission sexual behavior was reported at 6% of visits with detectable viremia. In multivariable regression modeling, correlates of transmission risk periods included younger age, lower CD4 cell count, low household asset ownership and increased internalized stigma.Although detectable viremia and/or sexual transmission risk behavior occurred in over half of individuals, ART reduced periods of HIV transmission risk by over 90% during up to 6 years of observation time. These findings provide further support for provision of ART, along with interventions to promote long-term adherence, to reduce HIV transmission in HIV-endemic settings.

SUBMITTER: Siedner MJ

PROVIDER: S-EPMC4038415 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Treatment as long-term prevention: sustained reduction in HIV sexual transmission risk with use of antiretroviral therapy in rural Uganda.

Siedner Mark J MJ Musinguzi Nicholas N Tsai Alexander C AC Muzoora Conrad C Kembabazi Annet A Weiser Sheri D SD Bennett John J Hunt Peter W PW Martin Jeffrey N JN Haberer Jessica E JE Bangsberg David R DR

AIDS (London, England) 20140101 2

<h4>Objectives</h4>Suppressive antiretroviral therapy (ART) substantially decreases HIV transmission in clinical research settings. We sought to measure the frequency and correlates of periods of transmission risk among individuals taking ART during multiple years of observation in rural, southwestern Uganda.<h4>Design</h4>Observational cohort study.<h4>Methods</h4>We collected sexual behavior and viral load data in a Ugandan cohort of people living with HIV/AIDS from the time of ART initiation. ...[more]

PMID: 24361683

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Project description:BACKGROUND:Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). OBJECTIVES:To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. SEARCH METHODS:We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. SELECTION CRITERIA:Randomised controlled trials (RCT), cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART DATA COLLECTION AND ANALYSIS: Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 3,833 references and examined 87 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. MAIN RESULTS:One RCT and nine observational studies were included in the review. These ten studies identified 2,112 episodes of HIV transmission, 1,016 among treated couples and 1,096 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350-550 cells/µL. Similarly, the summary rate ratio for the nine observational studies was 0.58 [95% CI 0.35, 0.96], with substantial heterogeneity (I(2)=64%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.36 [95% CI 0.17, 0.75] with substantial heterogeneity (I(2)=62%). We also performed subgroup analyses among the observational studies to see if the effect of ART on prevention of HIV differed by the index partner's CD4 cell count. Among couples in which the infected partner had ?350 CD4 cells/µL, we estimated a rate ratio of 0.12 [95% CI 0.01, 1.99]. In this subgroup, there were 247 transmissions in untreated couples and 30 in treated couples. AUTHORS' CONCLUSIONS:ART is a potent intervention for prevention of HIV in discordant couples in which the index partner has ?550 CD4 cells/µL. A recent multicentre RCT confirms the suspected benefit seen in earlier observational studies and reported in more recent ones. Questions remain about durability of protection, the balance of benefits and adverse events associated with earlier therapy, long-term adherence and transmission of ART-resistant strains to partners. Resource limitations and implementation challenges must also be addressed.Counselling, support, and follow up, as well as mutual disclosure, may have a role in supporting adherence, so programmes should be designed with these components. In addition to ART provision, the operational aspects of delivering such programmes must be considered.

Project description: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 HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis.ResultsIndex participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant.ConclusionsThe early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581 .).

Dataset Information

Treatment as long-term prevention: sustained reduction in HIV sexual transmission risk with use of antiretroviral therapy in rural Uganda.

Publications

Treatment as long-term prevention: sustained reduction in HIV sexual transmission risk with use of antiretroviral therapy in rural Uganda.

Similar Datasets

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