Person:

Mayer, Kenneth

Background. Antiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in “real-life” population-based settings in hyperendemic communities of sub-Saharan Africa, where health systems are typically resource-poor and overburdened, adherence to ART is often low, and partners commonly do not disclose their HIV status to each other. Methods. Data arose from a population-based open cohort in KwaZulu-Natal, South Africa. A total of 17 016 HIV-uninfected individuals present between January 2005 and December 2013 were included. Interval-censored time-updated proportional hazards regression was used to assess how the ART status affected HIV transmission risk in stable serodiscordant relationships. Results. We observed 1619 HIV seroconversions in 17 016 individuals, over 60 349 person-years follow-up time. During the follow-up period, 1846 individuals had an HIV-uninfected and 196 had an HIV-infected stable partner HIV incidence was 3.8/100 person-years (PY) among individuals with an HIV-infected partner (95% confidence interval [CI], 2.3–5.6), 1.4/100 PY (.4–3.5) among those with HIV-infected partners receiving ART, and 5.6/100 PY (3.5–8.4) among those with HIV-infected partners not receiving ART. Use of ART was associated with a 77% decrease in HIV acquisition risk among serodiscordant couples (adjusted hazard ratio, 0.23; 95% CI, .07–.80). Conclusions. ART initiation was associated with a very large reduction in HIV acquisition in serodiscordant couples in rural KwaZulu-Natal. However, this “real-life” effect was substantially lower than the effect observed in the HPTN-052 trial. To eliminate HIV transmission in serodiscordant couples, additional prevention interventions are probably needed.

Objectives: We investigate the effect of immediate antiretroviral therapy (ART) eligibility on HIV incidence among HIV-uninfected household members. Design: Regression discontinuity study arising from a population-based cohort. Methods: Household members of patients seeking care at the Hlabisa HIV Treatment and Care Programme in rural KwaZulu-Natal South Africa between January 2007 and August 2011 with CD4+ cell counts up to 350 cells/μl were eligible for inclusion if they had at least two HIV tests and were HIV-uninfected at the time the index patient linked to care (N = 4115). Regression discontinuity was used to assess the intention-to-treat effect of immediate versus delayed ART eligibility on HIV incidence among household members. Exploiting the CD4+ cell count-based threshold rule for ART initiation (CD4+ < 200 cells/μl until August 2011), we used Cox proportional hazards models to compare outcomes for household members of patients who presented for care with CD4+ cell counts just above versus just below the ART initiation threshold. Results: Characteristics of household members of index patients initiating HIV care were balanced between those with an index patient immediately eligible for ART (N = 2489) versus delayed for ART (N = 1626). There were 337 incident HIV infections among household members, corresponding to an HIV incidence of 2.4 infections per 100 person-years (95% confidence interval 2.5–3.1). Immediate eligibility for treatment reduced HIV incidence in households by 47% in our optimal estimate (hazard ratio = 0.53, 95% confidence interval 0.30–0.96), and by 32–60% in alternate specifications of the model. Conclusion: Immediate eligibility of ART led to substantial reductions in household-level HIV incidence.