What are the situational and behavioral factors associated with condomless anal sex without pre-exposure prophylaxis in MSM ?

Objective: This study aimed to identify situational and behavioral factors associated with condomless anal sex without on-demand PrEP in the open-label extension (OLE) study of the ANRS-IPERGAY trial. Methods: Univariable and multivariable modified Poisson regressions with a generalized estimating equation (GEE) were used. The attributable risk percentage for each explanatory variable and for condomless anal sex without PrEP was calculated. Results: In the OLE, 19% of anal intercourses were unprotected (i.e. no PrEP or condom). Of these, 85% were attributable to sexual intercourse with main partners and 47% with HIV-negative partners. The following factors were positively associated with condomless anal sex without PrEP: a depressive episode in the previous 12 months [aR (95% CI),P-value: 1.49 (1.02--2.17), 0.039], a higher number of sexual intercourses during the previous 4 weeks [1.01 [1.002--1.02], 0.014], and sexual intercourses under the influence of alcohol [1.45 (1.10--1.92), 0.008]. By contrast, condomless anal sex without PrEP was less frequent during sexual intercourses with known casual, unknown casual and multiple partners [0.20 (0.14--0.30), <0.001; 0.10 (0.05--0.20), <0.001; 0.11 (0.05--0.29), <0.001, respectively], as well as with HIV+ partners with an undetectable viral load and HIV+ partners with a detectable/unknown viral load or unknown serology status [0.57 (0.38--0.86), 0.007; 0.52 (0.32--0.87), 0.012, respectively]. Conclusion: Choosing to have condomless anal sex without PrEP depends primarily on the sexual partner's characteristics (level of intimacy, serological status). This reflects a form of rationality in HIV risk management. However, our results raise questions about the true efficacy of managing HIV risk using this approach

Changes in sexual behaviors in men who have sex with men : a comparison between the double-blind and open-label extension phases of the ANRS-IPERGAY trial

Pre-Exposure Prophylaxis (PrEP) is changing the landscape of HIV prevention, and may bring changes in sexual behaviors. The double-blind phase (DBP) and open-label extension (OLE) study of the ANRS-IPERGAY trial allowed us to assess changes in sexual behavior of men who have sex with men (MSM) taking sexual activity-based (i.e., on-demand) PrEP. Generalized Estimating Equation (GEE) models found a significant decrease in the number of sexual partners (Coefficient [CI95%], p value; - 0.37[- 0.70 to - 0.04], p = 0.03) between the DBP and OLE as well as in the number of sexual relations (- 0.25 [- 0.49 to 0.00], 0.04). GEE estimates also showed that respondents' most recent sexual relation was less likely to have been with an unknown casual partner during the OLE than during the DBP (Odds Ratio [CI95%], p value: 0.75[0.62-0.92], 0.005). Furthermore, they showed an increase in the proportion of condomless anal sex in the OLE (1.32[1.04-1.67], 0.02), a decrease in the proportion of 'suboptimal PrEP adherence' over time (0.75[0.58-0.97], p = 0.03), a decrease in PrEP only use (0.73[0.55-0.96], 0.03) and in both PrEP and condom use over time (0.70[0.51-0.95], 0.02) and finally, a decrease in alcohol consumption between the DBP and OLE (0.74[0.61-0.90], 0.002). We observed both protective and risky behaviors in terms of HIV and STI risk after on-demand PrEP uptake in the OLE phase. Our findings are consistent with results from previous PrEP trials

Uptake of PrEP and condom and sexual risk behavior among MSM during the ANRS IPERGAY trial

International audienceThe double-blind phase of the randomized ANRS IPERGAY trial, evaluating sexual activity-based oral HIV pre-exposure prophylaxis (PrEP), was conducted among high-risk men who have sex with men (MSM). Results showed an 86% (95% CI: 40–98) relative reduction in HIV incidence amongparticipants with tenofovir disoproxil fumarate–emtricitabine vs. placebo. The present pooled analysis aimed to analyze (i) participants’ adherence to the prescribed treatment and/or condom use during sexual intercourse and (ii) sexual behavior during the double-blind phase of the study. Four hundred MSM were enrolled in the trial. Every 2 months they completed online questionnaires collecting sexual behavior and PrEP adherence data regarding their most recent sexual intercourse. A total of 2232 questionnaires (M0–M24) were analyzed. Changes over time were evaluated using a mixed model accounting for multiple measures. Irrespective of sexual partner and practice type, on average, 42.6% (min: 32.1–max: 45.8%) reported PrEP use only during their most recent episode of sexual intercourse; 29% (22.9–35.6%) reported both PrEP and condom use; 11.7% (7.2–18.9%) reported condom-use only, and 16.7% (10.8–29.6%) reported no PrEP or condom use with no significant change during the study. Scheduled (i.e.,correct) PrEP use was reported on average by 59.0% (47.2–68.5%) of those reporting PrEP use during their most recent sexual intercourse. Overall, 70.3% (65.3–79.4%) and 69.3% (58.3–75.4%) of participants reported, respectively, condomless anal and condomless receptive anal intercourse during their most recent sexual encounter without significant change during followup. Overall, on average 83.3% (min: 70.4–max: 89.2%) of participants protected themselves by PrEP intake or condom use or both during the trial, and no increase in at-risk sexual practices was observed. None of these indicators showed significant trend during the follow-up, although we found a tendency toward decrease (p = .19) of the median number of sexual partners strengthening the absence of behavioral disinhibition. On-demand PrEP within a comprehensive HIV prevention package could improve prevention in MSM

On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial

International audienceBackground: ANRS IPERGAY found that on-demand pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine was associated with an 86% relative reduction of HIV-1 incidence compared with placebo among men who have sex with men at high risk of HIV. We aimed to investigate whether on-demand PrEP was similarly effective among individuals with lower exposure to HIV risk.Methods: Participants in the ANRS IPERGAY trial were randomly assigned to receive PrEP (fixed-dose combination of 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine per pill) or placebo. The primary endpoint was the diagnosis of HIV-1 infection. Pill uptake was assessed by counting returned pills at each follow-up and by estimating tenofovir concentration from frozen plasma samples. Participants were interviewed at each visit to assess the pattern of PrEP use. All participants enrolled in the modified intention-to-treat population of the double-blind phase of the ANRS IPERGAY trial were eligible for this post-hoc analysis. We calculated the total follow-up time for periods of less frequent sexual intercourse with high PrEP adherence (15 pills or fewer per month taken systematically or often during sexual intercourse). To estimate the time of HIV acquisition, fourth-generation HIV-1/2 ELISA assays, plasma HIV-1 RNA assays, and western blot analyses were done with use of frozen samples, and the stage of HIV infection was defined according to Fiebig staging. HIV incidence was compared between the two treatment groups among individuals who had less frequent sexual intercourse with high PrEP adherence. The ANRS IPERGAY trial is registered with ClinicalTrials.gov, NCT01473472.Findings: 400 participants who were randomly assigned to receive PrEP (n=199) or placebo (n=201) between Feb 22, 2012, and Oct 17, 2014, were included in this analysis. 270 participants had at least one period of less frequent sexual intercourse with high PrEP adherence during the study, representing 134 person-years of follow-up and 31% of the total study follow-up. During these periods, participants in both groups reported a median of 5·0 (IQR 2·0-10·0) episodes of sexual intercourse per month and used a median of 9·5 (6·0-13·0) pills per month. Six HIV-1 infections were diagnosed in the placebo group (HIV incidence of 9·2 per 100 person-years; 95% CI 3·4-20·1) and none were diagnosed in the tenofovir disoproxil fumarate plus emtricitabine arm (HIV incidence of 0 per 100 person-years; 0-5·4; p=0·013), with a relative reduction of HIV incidence of 100% (95% CI 39-100).Interpretation: A choice between daily or on-demand PrEP regimens could be offered to men who have sex with men who have less frequent sexual intercourse

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 openlabel 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 ondemand 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