Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial

Abstract

SummaryBackgroundRandomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect.MethodsPROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986).FindingsWe enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients.InterpretationIn this high incidence population, daily tenofovir–emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection.FundingMRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.

HIV-Positive–to–HIV-Positive Liver Transplantation

“…Worldwide a number of research studies in different populations have shown that consistent use of HIV-PrEP can be an efficacious and effective prevention intervention. Two European studies of oral PrEP using a combination of tenofovir and emtricitabine coformulated as Truvada (t) among men who have sex with men (PROUD trial [12] in the UK and the IPERGAY trial [13] in France) have reported during 2015. Both trials demonstrated a reduction in HIV acquisition of 86% in intent to treat analyses.…”

“…The evidence for efficacy and effectiveness of antiretroviral agents to reduce onward transmission from people who are HIV positive [14,16] as well as prevent HIV acquisition in those who are HIV free (HIV -Pre Exposure Prophylaxis HIV -PrEP) [12,13] continues to expand, making important additions to the prevention toolkit.…”

Problematising the Discourse of ‘Post-AIDS’

“…90% of all adults receiving ART were virally suppressed' (Yin, et al 2014, 5). In addition to treatment as prevention (TasP) significantly inhibiting the transmission of HIV (WHO 2015), prevention of infection is also made possible through post-exposure prophylaxis and the ongoing development (and availability) of PrEP (pre-exposure prophylaxis) -which brings with it the joint, yet contradictory, possibilities of control and protection alongside (HIV related) concerns of side effects and managing adherence and stigma (Liu et al 2014;Young et al 2014;McCormack et al 2015). These technical developments in HIV intervention generate their own complexities, requiring an acute and dynamic understanding of the relationships among HIV, medical technologies and the body (Rosengarten 2009).…”

“…The success of ART has reframed the lived experience of HIV undoubtedly but not entirely in the manner suggested by UNAIDS (2014) or indeed, Barack Obama in his most recent reference to the 'achievement of an AIDS-free generation' (PEPFAR 28 July 2015). The reasons for this are many and varied and highlight the social, economic and cultural limitations and shortcomings of clinical intervention and technologies (Hunter 2015;Johnson et al 2015). Nowhere is this more evident than in the experience of HIV and AIDS-related stigma.…”

“…In this paper, I aim to bring together a range of contemporary arguments to suggest that the notion of 'post-AIDS' is, at best, misplaced, not least because its starting point remains, primarily, a biotechnical one with anti-retroviral treatment (ART) and a myriad of medical (including male medical circumcision), pharmacological and other technologies at its heart. The discourse, or era, of 'post-AIDS', based on the narrative of 'positive progress' (Johnson et al 2015), is not one which can, or should, be embraced unproblematically, for it has the potential to oversimplify a highly complex condition and undermine the centrality of the social determinants and experience of HIV and AIDS. Whilst the 'post-AIDS' discourse includes a global public health message and set of targets directed primarily at the Global South, such as an 'AIDS-free' generation in Africa, I suggest that this (problematic) discourse also has resonance for the Global North where HIV arguably remains 'No Ordinary Mainstream Illness' (Persson et al 2014).…”