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Sexual behaviour of heterosexual men and women receiving antiretroviral pre-exposure prophylaxis for HIV prevention: a longitudinal analysis

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Summary

Background

Scarce data are available to assess sexual behaviour of individuals using antiretroviral pre-exposure prophylaxis for HIV prevention. Increased sexual risk taking by individuals using effective HIV prevention strategies, like pre-exposure prophylaxis, could offset the benefits of HIV prevention. We studied whether the use of pre-exposure prophylaxis in HIV-uninfected men and women in HIV-serodiscordant couples was associated with increased sexual risk behaviour.

Methods

We undertook a longitudinal analysis of data from the Partners PrEP Study, a double-blind, randomised, placebo-controlled trial of daily oral pre-exposure prophylaxis among HIV-uninfected partners of heterosexual HIV-serodiscordant couples (n=3163, ≥18 years of age). Efficacy for HIV prevention was publicly reported in July 2011, and participants continued monthly follow-up thereafter. We used regression analyses to compare the frequency of sex—unprotected by a condom—during the 12 months after compared with the 12 months before July 2011, to assess whether knowledge of pre-exposure prophylaxis efficacy for HIV prevention caused increased sexual risk behaviour.

Results

We analysed 56 132 person-months from 3024 HIV-uninfected individuals (64% male). The average frequency of unprotected sex with the HIV-infected study partner was 59 per 100 person-months before unmasking versus 53 after unmasking; we recorded no immediate change (p=0·66) or change over time (p=0·25) after July, 2011. We identified a significant increase in unprotected sex with outside partners after July, 2011, but the effect was small (average of 6·8 unprotected sex acts per year vs 6·2 acts in a predicted counterfactual scenario had patients remained masked, p=0·04). Compared with before July, 2011, we noted no significant increase in incident sexually transmitted infections or pregnancy after July, 2011.

Interpretation

Pre-exposure prophylaxis, provided as part of a comprehensive prevention package, might not result in substantial changes in risk-taking sexual behaviour by heterosexual couples.

Funding

The Bill & Melinda Gates Foundation and the US National Institute of Mental Health.

Introduction

Findings from four randomised trials have shown that oral antiretroviral pre-exposure prophylaxis is effective in protecting against HIV acquisition in diverse geographical and at-risk populations.1, 2, 3, 4 Evidence of the effectiveness of daily oral tenofovir-based pre-exposure prophylaxis in HIV prevention, and of coitally dependent tenofovir gel5 and antiretroviral treatment as prevention,6 has spurred optimism that the global HIV epidemic might be reversed. One important question for implementation of these prevention strategies after proof of effectiveness in trials is will they increase behavioural risk compensation, defined as individuals using known effective HIV prevention interventions engaging in increased sexual risk taking. A substantial increase in risky sexual behaviours by people using pre-exposure prophylaxis, and other HIV prevention strategies, could offset the HIV protective benefits7 and increase the risk of sexually transmitted infections (STIs). In clinical trials of pre-exposure prophylaxis, no significant differences in sexual behaviour between experimental and placebo groups were reported.1, 2, 3, 4, 8, 9, 10 However, because the comparison groups had equivalent uncertainty of treatment assignment and benefits of the study drug during the double-blind trial period, absence of risk compensation might not fully show sexual behaviour in the context of known pre-exposure prophylaxis efficacy.

In July, 2011, findings from the Partners PrEP Study,1 a randomised, double-blind, placebo-controlled trial of pre-exposure prophylaxis with daily oral tenofovir with or without emtricitabine among African heterosexual HIV uninfected members of serodiscordant couples, showed efficacy of pre-exposure prophylaxis for HIV prevention. Participants who had been assigned to the active pre-exposure prophylaxis groups continued in the study and were informed that they were receiving active pre-exposure prophylaxis and that this prevention strategy had been shown to reduce risk of HIV acquisition. HIV incidence in the placebo group during the study was 2% per year overall and 3% or more among subgroups with increased risk characteristics; assignment to pre-exposure prophylaxis resulted in a 67% (daily oral tenofovir) and 75% (emtricitabine and daily oral tenofovir) reduction in transmission risk, with a roughly 90% reduction in risk estimated for those adherent to pre-exposure prophylaxis. We examined sexual behaviours of individuals before and after July, 2011, to assess the potential risk compensation after they learnt about the effectiveness of pre-exposure prophylaxis for HIV prevention. We hypothesised that individuals using pre-exposure prophylaxis who were aware of its proven efficacy against HIV acquisition might increase sexual behavioural risks.

Section snippets

Partners PrEP Study

We undertook a longitudinal analysis of data from the Partners PrEP Study, which has been described previously (NCT00557245).1, 11 Briefly, between July, 2008, and November, 2010, 4747 HIV serodiscordant heterosexual couples were enrolled and followed up at nine research sites in Kenya and Uganda. Eligible HIV-uninfected participants were 18 years or older, sexually active, and had normal hepatic and renal function.

HIV-uninfected partners were randomly assigned (1:1:1) to daily oral tenofovir,

Results

Of 4747 HIV-uninfected participants enrolled and followed in the Partners PrEP Study, 3163 were initially randomly assigned to the clinical trial's active pre-exposure prophylaxis groups. Of these, 3024 were included in the present analysis; 139 were not included: 38 because they had seroconverted to HIV before July 13, 2011, and 101 because their final study visit (ie, completing the 36 months of follow-up or early withdrawal specified by the protocol) happened on or before July 13, 2011. At

Discussion

The transition from a double-blinded, placebo-controlled phase to one in which all participants were aware that they were receiving active, effective pre-exposure prophylaxis in the Partners PrEP Study provided a natural experiment to assess behavioural risk compensation in individuals receiving open-label pre-exposure prophylaxis for HIV prevention. Our data suggest that provision of pre-exposure prophylaxis as part of a comprehensive prevention package was not associated with substantial

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