Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study.

BACKGROUND: Data for on-demand pre-exposure prophylaxis (PrEP) are scarce. We implemented a cohort study to assess its efficacy, safety, and effect on sexual behaviour. METHODS: We invited men and transgender women who have sex with men, previously enrolled in the randomised placebo-controlled ANRS IPERGAY trial at seven sites (six in France and one in Canada), to participate in an open-label extension with on-demand tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) to be taken before and after sexual intercourse. We assessed the incidence of HIV and other sexually transmitted infections (STIs), PrEP adherence, safety, and sexual behaviour. Statistical analyses included comparisons of proportions and incidence between the randomised phase of the ANRS IPERGAY trial and the open-label phase, and all participants were included in safety analyses. ANRS IPERGAY is registered with ClinicalTrials.gov, number NCT01473472. FINDINGS: Between Nov 4, 2014, and Jan 27, 2015, we enrolled 361 participants. Median follow-up was 18·4 months (IQR 17·7-19·1). One participant who discontinued PrEP acquired HIV infection. HIV incidence was 0·19 per 100 person-years (95% CI 0·01-1·08), compared with 6·60 per 100 person-years (3·60-11·05) in the placebo group of the randomised study, indicating a relative reduction of 97% (95% CI 81-100) in the incidence of HIV with on-demand PrEP. Participants used a median of 18 pills of study drugs per month (IQR 11-25), and at the 6 month visit 240 (71%) of 336 participants had tenofovir detected in plasma. Drug-related gastrointestinal events were reported in 49 participants (14%) but were self-limited. Only four participants (1%) discontinued PrEP, three because of an increase in plasma creatinine. The proportion of participants reporting condomless sex at their last receptive anal intercourse significantly increased from 77% (136 of 176 participants) at baseline to 86% (66 of 77 participants) at 18 months' follow-up (p for trend=0·0004). The incidence of a first bacterial STI during this open-label phase did not change significantly compared with the randomised phase (59·0 vs 49·1 per 100 person-years, respectively; p=0·11). INTERPRETATION: On-demand oral PrEP is highly effective at preventing HIV infection among high-risk men who have sex with men and therefore represents an alternative to daily PrEP, expanding choices for HIV prevention. High rates of STIs resulting from low condom use did not undermine PrEP efficacy, but warrant frequent testing. FUNDING: ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the Canadian HIV Trials Network, Fonds Pierre Bergé-Sidaction, Gilead Sciences, and the Bill & Melinda Gates Foundation.

Optimizing the virological success of tenofovir DF/FTC/rilpivirine in HIV-infected naive and virologically suppressed patients through strict clinical and virological selection.

BACKGROUND: Tenofovir DF/FTC/rilpivirine (TDF/FTC/RPV) is a single tablet regimen considered as safe and efficacious in HIV population as long as food requirements, concomitant PPI administration, and compromised antiviral activity have been carefully reviewed. We evaluated TDF/FTC/RPV in a real-life setting with focus on clinical and virological outcomes. METHODS: OCEAN II is a prospective, two-centre observational study. From September 2012 to December 2013, antiretroviral-naive patients with HIV RNA <100,000 copies/mL or wishing to switch for simplification were considered for TDF/FTC/RPV. A systematic review of potential obstacles to TDF/FTC/RPV administration was undertaken during a multidisciplinary meeting, including DNA genotyping to detect archived RPV and/or NRTI-associated resistance mutations if historical RNA resistance testing was lacking. RESULTS: TDF/FTC/RPV was considered for 480 patients, however was not offered to 194 patients (40%), mainly because of risk of insufficient virological efficacy, issues on adherence, patient refusal, meal constraint, or PPI therapy. A total of 286 patients (269 in maintenance; 17 ART-naive) received TDF/FTC/RPV. After a median follow-up of 30 months, virological failure occurred in five patients (1.7%) without the emergence of resistance mutations. Discontinuation of TDF/FTC/RPV occurred in 98 patients, due to adverse events in 43 patients (44%) and non-safety reasons in 55 patients (56%). No grade three-fourth adverse events occurred. CONCLUSION: In this real-life experience, cohort consisting primarily of virologically suppressed patients, TDF/FTC/RPV usually maintained virologic suppression. Discontinuation of therapy because of intolerability was due to mild adverse events. Strict clinical and virological screening probably explained the low rate of virological failure.