Impact of Early Antiretroviral Treatment on Sexual Behaviour

A Randomised Comparison

Fiona C Lampe; Alison J Rodger; William Burman; Andrew Grulich; Gerald Friedland; Wafaa El Sadr; James Neaton; Giulio M. Corbelli; Sean Emery; Jean Michel Molina; Chloe Orkin; Jose Gatell; Jan Gerstoft; Kiat Ruxrungtham; Monica Barbosa de Souza; Andrew Phillips

Disclosures

AIDS. 2019;33(15):2337-2350. 

In This Article

Abstract and Introduction

Abstract

Background: Antiretroviral treatment (ART) reduces HIV infectiousness, but the effect of early ART on sexual behaviour is unclear.

Methods: We assessed, within the START randomised trial that enrolled HIV-positive adults with CD4>500/mm3, the effect of early (immediate) versus deferred ART on: (i) condomless sex with HIV-serodifferent partners (CLS-D); (ii) all condomless sex (CLS); (iii) HIV transmission-risk-sex (CLS-D-HIV-risk, defined as CLS-D and: not on ART or started ART <6 months ago or viral load(VL)>200c/mL or no VL in past 6 months), during two year follow-up. Month-12 CLS-D (2010–2014) was the primary outcome.

Results: Among 2562 MSM, there was no difference between immediate and deferred arms in CLS-D at month 12 [12.6% versus 13.1%; difference (95% CI):-0.4%(-3.1%, 2.2%),p=0.75] or month 24, or in CLS. Among 2010 heterosexual men and women, CLS-D at month 12 tended to be higher in the immediate versus deferred arm [10.8% versus 8.3%; difference:2.5%(-0.1%, 5.2%),p=0.062]; the difference was greater at month 24 [9.3% versus 5.6%; difference:3.7%(1.0%, 6.4%),p=0.007], at which time CLS was higher in the immediate arm [20.7% versus 15.7%,p=0.013]. CLS-D-HIV-risk at month 12 was substantially lower in the immediate versus deferred arm for MSM [0.2% versus 11.0%; difference:-10.7%(-12.5%, -8.9%),p<0.001] and heterosexuals [0.6% versus 7.7%; difference:-7.0%(-8.8%, -5.3%),p<0.001], due to viral suppression on ART.

Conclusions: A strategy of early ART had no effect on condomless sex with HIV-serodifferent partners among MSM, but resulted in modestly higher prevalence among heterosexuals. However, among MSM and heterosexuals, early ART resulted in a substantial reduction in HIV-transmission-risk-sex, to a very low absolute level.

Introduction

In 2015, results were published from the START (Strategic Timing of Antiretroviral Treatment Trial)[1,2] and TEMPRANO[3] randomised trials, demonstrating that a strategy of immediate ART (regardless of CD4 cell count) for people with diagnosed HIV reduced serious morbidity and mortality compared to ART deferral. Guidelines that had previously set CD4 thresholds for ART initiation were changed to recommend ART initiation for all adults with HIV at any CD4 level.[4–6] US guidelines had already recommended such a strategy, primarily based on evidence from observational studies.[7]

Prior to this conclusive evidence of the clinical benefit of early ART, results had been accumulating regarding the protective effect of ART on HIV transmission. Initially, a number of observational studies demonstrated a marked association between the viral load (VL) of an HIV-positive person and the risk of HIV transmission to an HIV-negative partner.[8–12] In 2011, unequivocal evidence came from the HPTN 052 randomised trial, which demonstrated that use of early ART for the HIV-positive partner of serodifferent couples was associated with a 96% reduction in transmissions to the HIV-negative partner.[13] Subsequently, the PARTNER,[14] PARTNER2[15] and Opposites Attract[16] prospective observational studies provided crucial information on transmission risk specifically through condomless sex (CLS), including anal CLS, among HIV serodifferent heterosexual and MSM couples. In each of these studies, there were no within-couple linked HIV transmissions during eligible follow-up in which couples reported CLS and the HIV-positive partner was virally suppressed on ART. Together these studies have provided the necessary evidence for assurance that HIV-positive people on ART with undetectable VL cannot transmit HIV (Undetectable=Untransmittable; Prevention Access Campaign).[17]

As knowledge regarding the protective effect of VL suppression on HIV infectiousness has been disseminated and publicized, and in particular since the 'Swiss Statement' in 2008,[18] it has been debated whether such knowledge impacts on sexual behaviour and patterns of condom use among people taking ART.[19–21] Initially the concern was that if viral suppression on ART led merely to a reduction in (rather than elimination of) HIV transmission risk, any increase by the HIV-positive individual in CLS with HIV-serodifferent partners (CLS-D) could partially negate the benefit of ART.[19,20] Recent findings have provided reassurance on this point, demonstrating no transmission risk in this context.[14–16] However an increase in CLS-D associated with ART use may still be concerning in the context of sub-optimal ART adherence, infrequent VL monitoring, inaccurate knowledge of personal VL status[22] or poor knowledge of the importance of viral suppression, a key issue in early treatment.[23] Furthermore, any changes in patterns of CLS overall may have implications for transmission of other sexually transmitted infections (STIs). It is also conceivable that reductions in condom use among HIV-positive people may affect condom use among HIV-negative people with partners of unknown HIV status.

There is, to date, little compelling evidence that ART use leads to higher levels of condomless sex among people with HIV. Findings from some observational studies have suggested that, in some contexts or subgroups, condom use may be influenced by knowledge of viral suppression.[24–29] However, in most studies, overall, levels of CLS-D were similar or lower among people on ART compared to those not on ART (or among people with undetectable compared to detectable VL).[28–46] Two randomised trials have provded data on this issue;[47,48] neither supports the hypothesis that ART use leads to increased CLS-D. However, it is important to reeavualte this association as patterns of sexual behaviour may have changed with increasing awareness of the protective effect of suppressed VL, paritcularly since publication of HPTN 052 in 2011.[13] Furtherore, now that the protective effect of viral suppression on HIV transmission is assured, it is necessary to consider measures additional to CLS-D, that capture sex with risk of HIV-transmission by accounting for viral suppression.[45,47–49] When considering risk of other STIs, CLS overall is the most relevant measure.

We previously reported on sexual behaviour at enrolment in the START trial.[50] We now assess, separately among MSM and heterosexual individuals, the effect of a strategy of early ART compared to ART deferral on sexual behaviour in the first two years of follow-up, considering: CLS-D at month 12 (the pre-defined primary outcome), CLS, CLS-D with risk of HIV transmission, and other measures.

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