PrEP is effective in a real world setting

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.

McCormack S, Dunn DT, Desai M, Dolling DI, Gafos M, Gilson R, Sullivan AK, Clarke A, Reeves I, Schembri G, Mackie N, Bowman C, Lacey CJ, Apea V, Brady M, Fox J, Taylor S, Antonucci S, Khoo SH, Rooney J, Nardone A, Fisher M, McOwan A, Phillips AN, Johnson AM, Gazzard B, Gill ON. Lancet. 2015 Sep 9. pii: S0140-6736(15)00056-2. doi: 10.1016/S0140-6736(15)00056-2. [Epub ahead of print]

Background: Randomised 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.

Methods: PROUD 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).

Findings: We 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.

Interpretation: In 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.

Abstract [1]  Full-text [free] access [2]

Editor’s notes: The PROUD study was an open label pragmatic randomised controlled trial designed to assess the effectiveness of pre-exposure prophylaxis (PrEP) in gay men and other men who have sex with men and whether the benefits are counteracted by risk compensation in users of PrEP. During the pilot phase of the study to test the feasibility of a large-scale trial the investigators found an unexpectedly high incidence of HIV infections. It was seven times higher than the national estimate reported for gay men and other men who have sex with men in the UK. The incidence of HIV infection was significantly lower in the group assigned to receive PrEP immediately, compared with the group assigned to receive it after a deferral period of one year. Moreover the reduction in HIV incidence was greater than has been observed in placebo-controlled trials. As a result the trial was stopped early on the recommendation of the trial steering committee. The high incidence of HIV suggests that, despite the broad eligibility criteria, the study population was highly selective and that the offer of PrEP attracted men who were at high risk of HIV and most likely to benefit from it. Despite some limitations, for example, lack of data on adherence and sexual behaviour, the results of this study are encouraging and have important implication for HIV prevention. They indicate that PrEP is effective in a real world setting, particularly in a population that is aware of its risk of HIV infection. Furthermore, there was no evidence of risk compensation among PrEP recipients. 

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