The Lancet has published the results of the PROUD study, which shows giving daily HIV medication to gay men who are HIV negative yet at high risk of becoming HIV positive is highly effective at preventing new infections. The authors, led by Professor Sheena McCormack, of the Medical Research Council (MRC) Clinical Trials Unit at University College London, UK, say that PrEP should now be added to the HIV prevention toolkit for men who have sex with men at risk of HIV infection as soon as possible in the UK and elsewhere.
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, meaning they increase risky sexual behaviour in the belief that the HIV medication is protecting them. The authors did a pilot study to assess the feasibility of an open-label trial of PrEP.
PROUD was an open-label randomised trial done at 13 sexual health clinics in England. It enrolled HIV negative gay men who had had at least one episode of receptive or insertive 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) (also known as Truvada) either immediately (275 patients) or after a deferral period of 1 year (269 patients). Follow-up was quarterly.
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 (known as PEP) in the deferred group. Thus people in the immediate group had an 86% relative reduction in risk of acquiring HIV compared with the deferred group. The results suggest that 13 men in a similar population would need to be offered 1 year of PrEP to avert one HIV infection. The 28 recorded adverse events that led to an interruption in PrEP included nausea and headache, but there were no serious adverse events deemed related to study drug.
The prevalence of sexually transmitted infections, including syphilis, rectal gonorrhoea or chlamydia, did not differ significantly between groups despite a suggestion of risk compensation among a small proportion of PrEP recipients. A total of 152 such infections occurred in the immediate group compared with 124 in the deferred group, which after adjustment for the larger number of screens in the immediate group was not statistically significant.
The incidence of new infections recorded in the deferred group was roughly seven-times higher than the national estimate of 1·34 cases per 100 person-years reported for men who have sex with men attending sexual health clinics in the UK 2012. Although participants in PROUD were much more likely to have had rectal infections and to have used post-exposure prophylaxis than was the overall population of men who have sex with men attending sexual health clinics, the authors say the size of the difference in HIV incidence was still surprising. The authors say: "The difference suggests that the PROUD study population was highly selective, despite broad eligibility, and that the offer of PrEP generally attracts those men who are most likely to benefit from it. This finding is highly encouraging for PrEP implementation, although quantifying the likely demand in the UK remains challenging."
They highlight an economic assessment based on a mathematical model adapted to the UK HIV epidemic in men who have sex with men suggests that providing targeted PrEP to this group from 2016 would be cost-effective at current prices, or without targeted implementation if Truvada was half the price.
They conclude: "The impressive reduction in HIV incidence in people taking PrEP, without a measurable increase in other sexually transmitted infections, is reassuring for clinical, community, and public health stakeholders. National health services are under financial constraints, but they cannot afford to ignore the results of PROUD and IPERGAY, which strongly support the addition of PrEP to the current standard of prevention for men who have sex with men at risk of HIV infection."
Writing in a linked Comment, Dr Kenneth Mayer, The Fenway Institute, Fenway Health, Boston, MA, USA and Harvard Medical School, Boston, MA, USA, and Dr Chris Beyrer, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA, conclude: "The PROUD results show that PrEP should be part of the range of services offered by any clinical programme that focuses on sexual health. The time for cautionary speculation is over: HIV prevention services should be expanded worldwide by offering PrEP routinely to those who could benefit."
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