Impact of universal testing and treatment on sexual risk behaviour and herpes simplex virus type 2: a prespecified secondary outcomes analysis of the HPTN 071 (PopART) community-randomised trial

Abstract

Background: Comprehensive HIV prevention strategies have raised concerns that knowledge of interventions to reduce risk of HIV infection might mitigate an individual's perception of risk, resulting in riskier sexual behaviour. We investigated the prespecified secondary outcomes of the HPTN 071 (PopART) trial to determine whether a combination HIV prevention strategy, including universal HIV testing and treatment, changed sexual behaviour; specifically, we investigated whether there was evidence of sexual risk compensation.

Methods: HPTN 071 (PopART) was a cluster-randomised trial conducted during 2013-18, in which we randomly assigned 21 communities with high HIV prevalence in Zambia and South Africa (total population, approximately 1 million) to combination prevention intervention with universal antiretroviral therapy (ART; arm A), prevention intervention with ART provided according to local guidelines (universal since 2016; arm B), or standard of care (arm C). The trial included a population cohort of approximately 2000 randomly selected adults (aged 18-44 years) in each community (N=38 474 at baseline) who were followed up for 36 months. A prespecified secondary objective was to evaluate the impact of the PopART intervention compared with standard of care on herpes simplex virus type 2 (HSV-2) and sexual behaviour (N=20 422 completed final visit). Secondary endpoints included differences in sexual risk behaviour measures at 36 months and were assessed using a two-stage method for matched cluster-randomised trials. This trial is registered with ClinicalTrials. gov, number NCT01900977.

Findings: The PopART intervention did not substantially change probability of self-reported multiple sex partners, sexual debut, or pregnancy in women at 36 months. Adjusted for baseline community prevalence, reported condomless sex was significantly lower in arm A versus arm C (adjusted prevalence ratio 0·80 [95% CI 0·64-0·99]; p=0·04) but not in arm B versus arm C (0·94 [0·76-1·17]; p=0·55). 3-year HSV-2 incidence was reduced in arm B versus arm C (adjusted risk ratio 0·76 [95% CI 0·63-0·92]; p=0·010); no significant change was shown between arm A versus arm C (0·89 [0·73-1·08]; p=0·199).

Interpretation: We found little evidence of any change in sexual behaviour owing to the PopART interventions, and reassuringly for public health, we saw no evidence of sexual risk compensation. The findings do not help to explain the differences between the two intervention groups of the HPTN 071 (PopART) trial.

Funding: National Institute of Allergy and Infectious Diseases, the National Institutes of Health, the International Initiative for Impact Evaluation (3ie), the Bill & Melinda Gates Foundation, the US President's Emergency Plan for AIDS Relief, and the Medical Research Council UK.

Conflict of interest statement

Declaration of interests HA and DD report on behalf of the entire study team, grant funding from: the NIH, the international initiative for impact evaluation (3ie), the US President's Emergency Plan for AIDS Relief (PEPFAR), and the Bill & Melinda Gates Foundation (also reflected in Acknowledgments). HA reports membership in the technical review panel for the Global Fund. NB-M is a member on the HPTN Ethics Working Group. All other authors declare no competing interests.

Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1

Enrolment and follow-up of outcome-specific cohorts Arm A=combination prevention intervention with universal antiretroviral therapy. Arm B= combination prevention intervention with antiretroviral therapy provided according to local guidelines (universal since 2016). Arm C=standard of care. HSV-2=herpes simplex virus type 2.

Figure 2

Community-level mean prevalence of HSV-2 and self-reported sexual risk (A) Self-reported multiple sex partners, condomless last sex, and HSV-2-positive status among participants in arm A, arm, B, and arm C at baseline (at enrolment). (B) Self-reported multiple sex partners, condomless last sex, HSV-2 incidence, sexual debut during the HPTN 071 (PopART) study, and current pregnancy among participants in arm A, arm B, and arm C at month 36. HSV-2 incidence is cumulative over 3 years, among participants who were HSV-2 negative at baseline. HSV-2=herpes simplex virus type 2.