UK PROUD study published as open access article in The Lancet: PrEP dramatically reduces risk of HIV
Gareth Hardy, HIV iBase
Results from the UK PROUD study are now published as an open access article on 9th September in the Lancet. 
This follows their earlier presentation at in February 2015 at CROI  showing that oral pre-exposure prophylaxis (PrEP) dramatically reduces the risk of HIV infection in gay men and transgender women by who are at significant HIV risk. In addition, there were no cases of HIV transmsion in people actively using PrEP and no evidence of increased high risk sex.
PrEP consists of two antiretroviral drugs, tenofovir and emtricitabine (FTC), coformulated in a single pill (Truvada).
PROUD is an open label, randomised clinical trial conducted at 13 sexual health clinics in England. Participants were randomised to receive PrEP either immediately, or after one year deferral. Entry criteria included being at high risk of infection defined as recent receptive anal sex without a condom in the previous 90 days. Participants were prescribed PrEP on a rolling 90 day basis, after an initial 30 day prescription and asked to attend clinic every three months in which they would be tested for HIV and bacterial STIs. In addition, participants were asked to complete monthly questionnaires and daily diaries about sexual behaviour and PrEP adherence.
PROUD used an open label design to test the effectiveness of PrEP in a real-life setting. The results in the Lancet paper are from a pilot phase of PROUD, intended to assess feasibility of recruitment and retention for an efficacy trial. The larger study was estimated to need 5000 participants to detect a 50% reduction in new HIV infections. However, the unexpectedly large difference in HIV infections between the immediate and deferred arms of the study, driven by higher HIV incidence overall, meant that efficacy could be demonstrated.
In October 2014, while still in the pilot phase, the trial steering committee recommended that the study design was changed to close recruitment and give immediate access to PrEP to all participants in the deferred PrEP group (n=163). PROUD will continue to follow all participants until the final enrolled participant has completed 2 years follow up.
The study recruited 544 participants, of which 275 were in the immediate group and 269 were in the deferred group. At the time of reporting, HIV incidence follow up data was complete for 243 (94%) of 259 patient years in the immediate group and 222 (90%) of 245 patient years in the deferred group.
Three HIV infections occurred in the immediate group (1.2/100 person years) as compared to 20 in the deferred group (9/100 person years), representing a relative a reduction of 86% (90% CI: 64 to 96, p=0.0001). These figures mean that 13 individuals in a similar group would need to be taking PrEP for one year to avert one new acquisition of HIV.
The new infections in the deferred group occurred despite 174 prescriptions of post-exposure prophylaxis (PEP). Of the twenty participants who became newly infected in the deferred group, six had received a total of 12 courses of PEP. Of the three participants who became infected in the immediate group, one had a positive HIV test at week 4 of the study and is thought to have been infected before enrolment. The other two participants tested HIV positive much later in the study after many months of not returning for PrEP prescriptions. These results suggest that no HIV infections occured in people who were actively taking PrEP.
Sexual behaviour questionnaires at year one of the study revealed that 21% of participants randomised to the immediate group reported receptive anal sex without a condom with 10 or more partners versus 12% in the deferred group (p=0.03). Regardless of this, diagnoses of bacterial STIs occurred in 152 (57%) of 265 participants in the immediate group and 124 (50%) of 247 participants in the deferred group. After adjustment for the number of study screens in each group, no significant difference was found between the groups for incidence of bacterial STIs. Importantly the incidence of rectal gonorrhoea or chlamydia, indicators of receptive anal intercourse without condoms, were similar in both groups.
None of the participants of either group who became HIV positive, had resistance mutations to either emtricitabine or tenofovir, apart from the participant who tested positive at week 4 and was suspected to have been infected before enrolment. This person had the M184V mutation associated with resistance to FTC.
PROUD showed that PrEP is highly effective in a real-life setting and importantly is not associated with increased risk-taking in this group. Economic modelling based on the UK epidemic in MSM suggests that PrEP would be cost effective at current drug pricing in a similarly risk-matched group and that wider use by people with lower HIV risk would also be cost effective if the current price of Truvada was dropped by 50%. 
The reduced dosing used in the French IPERGAY study would lower costs further but data on efficacy is still needed before this can be routinely recommended. 
The earlier report on PrEP studies at IAS 2015 in this issue of HTB includes a discussion of PrEP dosing.
- McCormack S et al. 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. The Lancet. Sept 9 2015.
- Collins S. PrEP reduced HIV risk by at least 86% in PROUD: no transmissions likely from people taking meds. HTB March/April 2015.
- Cambiano V et al. Is pre-exposure prophylaxis for HIV prevention cost-effective in men who have sex with men who engage in condomless sex in the UK? BASHH Spring Conference 2015; June 1–3, 2015; Glasgow, UK. Abstract O1.
- Molina J-M et al. On demand PrEP with oral TDF-FTC in MSM: results of the ANRS IPERGAY trial. Conference on Retroviruses and Opportunistic Infections; Feb 23–26, 2015; Seattle, WA, USA. Abstract 23LB.
- Collins S. The PrEP experience: IAS 2015 and beyond. HTB September/October 2015.