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Antiretroviral-based HIV-1 prevention: antiretroviral treatment and pre-exposure prophylaxis

Connie Celum, Jared M Baeten

Corresponding author name: Connie Celum
Corresponding author e-mail: ccelum@uw.edu

Citation: Antiviral Therapy 2012; 17:1483-1493
doi: 10.3851/IMP2492

Date accepted: 14 April 2012
Date published online: 07 December 2012

Abstract

Antiretroviral-based HIV-1 prevention strategies – including antiretroviral treatment (ART) to reduce the infectiousness of individuals with HIV-1 and oral and topical pre-exposure prophylaxis (PrEP) for uninfected individuals to prevent HIV-1 acquisition – are the most promising new approaches for decreasing HIV-1 spread. Observational studies among HIV-1 serodiscordant couples have associated ART initiation with a reduction in HIV-1 transmission risk of 80–92%, and a recent randomized trial demonstrated that earlier initiation of ART (that is, at CD4+ T-cell counts between 350 and 550 cells/mm3), in the context of virological monitoring and adherence support, resulted in a 96% reduction in HIV-1 transmission. A number of ongoing and recently-completed clinical trials have assessed the efficacy of PrEP for HIV-1 prevention as pericoitally administered or daily-administered 1% tenofovir gel and daily oral tenofovir disoproxil fumarate (TDF) and combination emtricitabine (FTC)/TDF. Completed studies have demonstrated HIV-1 protection efficacies ranging from 39% to 75%. However, two trials in African women have shown no HIV-1 protection with TDF and FTC/TDF PrEP; the reasons for lack of efficacy in those trials are being investigated. Adherence is likely the key to efficacy of antiretrovirals for HIV-1 prevention, both as ART and PrEP. Critical unanswered questions for successful delivery of antiretroviral-based HIV-1 prevention include how to target ART and PrEP to realize maximum population benefits, whether HIV-1-infected individuals at earlier stages of infection would accept ART to reduce their risk for transmitting HIV-1 and whether highest-risk HIV-1-negative persons would use PrEP, and whether high adherence could be sustained to achieve high effectiveness.

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