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Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

ABSTRACT: Antiretroviral drugs that inhibit viral replication were expected to reduce transmission of HIV by lowering the concentration of HIV in the genital tract. In 11 of 13 observational studies, antiretroviral therapy (ART) provided to an HIV-infected index case led to greatly reduced transmission of HIV to a sexual partner. In the HPTN 052 randomised controlled trial, ART used in combination with condoms and counselling reduced HIV transmission by 96·4%. Evidence is growing that wider, earlier initiation of ART could reduce population-level incidence of HIV. However, the full benefits of this strategy will probably need universal access to very early ART and excellent adherence to treatment. Challenges to this approach are substantial. First, not all HIV-infected individuals can be located, especially people with acute and early infection who are most contagious. Second, the ability of ART to prevent HIV transmission in men who have sex with men (MSM) and people who use intravenous drugs has not been shown. Indeed, the stable or increased incidence of HIV in MSM in some communities where widespread use of ART has been established emphasises the concern that not enough is known about treatment as prevention for this crucial population. Third, although US guidelines call for immediate use of ART, such guidelines have not been embraced worldwide. Some experts do not believe that immediate or early ART is justified by present evidence, or that health-care infrastructure for this approach is sufficient. These concerns are very difficult to resolve. Ongoing community-based prospective trials of early ART are likely to help to establish the population-level benefit of ART, and-if successful-to galvanise treatment as prevention.

SUBMITTER: Cohen MS

PROVIDER: S-EPMC3880570 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

Cohen Myron S MS Smith M Kumi MK Muessig Kathryn E KE Hallett Timothy B TB Powers Kimberly A KA Kashuba Angela D AD

Lancet (London, England) 20131023 9903

Antiretroviral drugs that inhibit viral replication were expected to reduce transmission of HIV by lowering the concentration of HIV in the genital tract. In 11 of 13 observational studies, antiretroviral therapy (ART) provided to an HIV-infected index case led to greatly reduced transmission of HIV to a sexual partner. In the HPTN 052 randomised controlled trial, ART used in combination with condoms and counselling reduced HIV transmission by 96·4%. Evidence is growing that wider, earlier initi ...[more]

PMID: 24152938

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Project description:IntroductionSuccessful management of pediatric and adult human immunodeficiency virus (HIV) disease includes lifelong administration of antiretroviral therapy (ART). The need for the continuous use of antiretroviral drugs throughout the life course poses a challenge to children, adolescents, and adults living with HIV and their caregivers. Historically, treatment interruptions have been viewed as a negative therapeutic strategy. Recently, however, treatment interruptions or treatment reduction strategies have become a focus of investigations as innovative approaches to the long-term management of HIV disease. Current challenges with treatment interruptions include identifying an appropriate timeframe for length of interruptions and identifying HIV patient populations in whom the treatment interruption can be successful.ObjectiveIn this review, we aimed at summarizing recent studies of planned and unplanned treatment interruptions in children and adults living with HIV.Materials and methodsWe searched two databases (PubMed and Cochrane Controlled Trials Register) using keywords (HIV OR AIDS OR acquired immunodeficiency syndrome OR HIV-1 OR antiretroviral) AND (treatment interruption OR planned interruption OR therapeutic interruption OR unplanned interruption), for published randomized and nonrandomized clinical trials and observational cohort studies in children and adults (from birth to 99 years of age) in global settings covering a period from 2012 to 2018. In this review, only the studies that contained pediatric and adolescent populations with baseline immunological, virological, and clinical characteristics and outcomes after treatment interruption were included.ResultsA total of 174 eligible citations from the two databases were identified. We identified 10 prospective treatment interruption studies on children (five studies) and adults (five studies) during 2012-2018 with a total of 863 pediatric and 273 adult subjects. Collectively, recent studies on children and adults with HIV infection suggest that treatment interruptions with proper monitoring can be successful by instituting well-defined immunological and virological parameters or thresholds such as CD4 count, CD4%, and HIV RNA viral load that identify low-risk populations with treatment failure. In addition to standard virological and immunological outcome measurements, selected biomarkers that help detect early immune activation may also be useful in the monitoring of treatment interruption.ConclusionTreatment interruptions in adult and especially pediatric patients with well-controlled HIV disease may provide an alternative opportunity to optimize long-term HIV management by minimizing drug-associated toxicity and improving long-term adherence and quality of life.

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.

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Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

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Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

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