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Heterosexual HIV-1 Infectiousness and Antiretroviral Use: Systematic Review of Prospective Studies of Discordant Couples

Baggaley, Rebecca F.a; White, Richard G.b; Hollingsworth, T. Déirdrea; Boily, Marie-Claudea

doi: 10.1097/EDE.0b013e318276cad7
Infectious Disease

Background: Recent studies have estimated the reduction in HIV-1 infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized controlled trials, accompanied by rigorous adherence counseling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings.

Methods: We attempted to summarize the effect of ART on HIV transmission by undertaking a systematic review and meta-analysis of HIV-1 infectiousness per heterosexual partnership (incidence rate and cumulative incidence over study follow-up) estimated from prospective studies of discordant couples. We used random-effects Poisson regression models to obtain summary estimates. When possible, the analyses were further stratified by direction of transmission (man-to-woman or woman-to-man) and economic setting (high- or low-income countries). Potential causes of heterogeneity of estimates were explored through subgroup analyses.

Results: Fifty publications were included. Nine allowed comparison between ART and non-ART users within studies (ART-stratified studies), in which summary incidence rates were 3.6/100 person-years (95% confidence interval = 2.0–6.5) and 0.2/100 person-years (0.07–0.7) for non-ART- and ART-using couples, respectively (P < 0.001), constituting a 91% (79–96%) reduction in per-partner HIV-1 incidence rate with ART use. The 41 studies that did not stratify by ART use provided estimates with high levels of heterogeneity (I 2 statistic) and few reported levels of ART use, making interpretation difficult. Nevertheless, estimates tended to be lower with ART use. Infectiousness tended to be higher for low-income than high-income settings, but there was no clear pattern by direction of transmission (man-to-woman and woman-to-man).

Conclusions: ART substantially reduces HIV-1 infectiousness within discordant couples, based on observational studies, and could play a major part in HIV-1 prevention efforts. However, the non-zero risk from partners receiving ART demonstrates that appropriate counseling and other risk-reduction strategies for discordant couples are still required. Additional estimates of ART effectiveness by adherence level from real-life settings will be important, especially for persons starting treatment early without symptoms.

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From the aDepartment of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London; and bDepartment of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School Of Hygiene and Tropical Medicine, London, United Kingdom.

Submitted 12 October 2012; accepted 17 July 2012.

This work was supported by the Wellcome Trust (R.F.B., grant number WT082623MA), UK Medical Research Council (R.G.W., Methodology Research Fellowship grant number G0802414), the Bill and Melinda Gates Foundation (R.G.W., grant number 19790.01), the EU FP7 (R.G.W., grant number 242061), and Imperial College London Junior Research Fellowship Programme (T.D.H.).

The authors report no conflicts of interest.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article ( This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Rebecca Baggaley, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, St Mary’s Campus, Norfolk Place, London W2 1PG, United Kingdom. E-mail:

© 2013 Lippincott Williams & Wilkins, Inc.