Hepatitis A and B vaccine uptake and immunisation among men who have sex with men seeking PrEP: a substudy of the ANRS IPERGAY trial.

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended in men who have sex with men (MSM). We assessed HAV and HBV vaccine uptake in the non-immune participants and their immunisation during follow-up of the ANRS IPERGAY (Intervention Préventive de l'Exposition aux Risques avec et pour les Gays) pre-exposure prophylaxis (PrEP) trial.During the ANRS IPERGAY trial among MSM (NCT01473472), vaccination against HAV and HBV was offered free of charge to all non-immune participants at baseline. We assessed anti-HAV IgGs and anti-hepatitis B surface (HBs) antibodies (Abs) at baseline, 1-3 months after each vaccine dose and on the last follow-up visit. Vaccination uptake and immunisation were analysed in non-immune participants with at least 6 months of follow-up after the 1st vaccine dose.A total of 427 MSM with a median age of 34.8 years were analysed. Median follow-up was 2.2 years (Q1-Q3, 1.6-2.9). Absence of anti-HAV IgG at baseline (50.4%, 215/427) was associated with younger age (p=0.0001). Among HAV non-immune participants, 96.1% (197/205) received one or more vaccine doses and 91.0% (172/189) received two vaccine doses. Among HBV non-immune participants, 97.6 % (81/83) received one or more vaccine doses and 78.4% (58/74) received three doses. On the last-visit sample, anti-HAV IgG and anti-HBs Abs were respectively detected in 94.8% (95% CI 90.0% to 97.7%) and 79.6% (95% CI 66.5% to 89.4%) of participants with complete vaccination and in 80.0% (95% CI 51.9% to 95.7%) and 40.0% (95% CI 16.3% to 67.7%) of participants with incomplete vaccination.Vaccine acceptability against HAV and HBV infections was very high in MSM starting PrEP. Immunisation was high in participants with a full vaccination scheme. Physicians must consider PrEP visits as major opportunities to propose and complete HAV and HBV vaccination in at-risk non-immune subjects.

High Prevalence and High Rate of Antibiotic Resistance of Mycoplasma genitalium Infections in Men Who Have Sex With Men: A Substudy of the ANRS IPERGAY Pre-exposure Prophylaxis Trial.

BACKGROUND: Mycoplasma genitalium (MG) is an emerging pathogen among men who have sex with men (MSM) with raising rates of antibiotic resistance. This study assessed the prevalence and incidence of MG infection in MSM enrolled in the open-label phase of the ANRS IPERGAY trial with on-demand tenofovir disoproxil fumarate/emtricitabine for human immunodeficiency virus prevention and the impact of doxycycline post-exposure prophylaxis (PEP). METHODS: 210 subjects were tested at baseline and at 6 months by real-time PCR assays for MG detection in urine samples and oropharyngeal and anal swabs. Resistance to azithromycin (AZM), to fluoroquinolones (FQs), and to doxycycline was investigated in the French National Reference Center of Bacterial Sexually Transmitted Infections (STIs). RESULTS: The all-site prevalence of MG at baseline was 10.5% (6.3% in urine samples, 4.3% in anal swabs, 0.5% in throat swabs) and remained unchanged at 6 months whether or not PEP was used: 9.9% overall, 10.2% with PEP, 9.6% without. The overall rate of MG resistance (prevalent and incident cases) to AZM and FQs was 67.6% and 9.1%, respectively, with no difference between arms. An in vivo mutation of the MG 16S rRNA, which could be associated with tetracycline resistance, was observed in 12.5% of specimens tested. CONCLUSIONS: The prevalence of MG infection among MSM on pre-exposure prophylaxis was high and its incidence was not decreased by doxycycline prophylaxis with a similar high rate of AZM and FQ resistance, raising challenging issues for the treatment of this STI and supporting current recommendations to avoid testing or treatment of asymptomatic MG infection.

Prevalence and Incidence of Human Papillomavirus Infection in Men Having Sex With Men Enrolled in a Pre-exposure Prophylaxis Study: A Sub-study of the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales "Intervention Préventive de l'Exposition aux Risques avec et pour les hommes Gays" Trial.

BACKGROUND: Human papillomavirus (HPV) infection is more frequent in men having sex with men (MSM) who are living with human immunodeficiency virus (HIV) than in MSM without HIV. There are currently no data regarding HPV infections in preexposure prophylaxis (PrEP)-using MSM. METHODS: MSM living without HIV who were enrolled in the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales "Intervention Préventive de l'Exposition aux Risques avec et pour les hommes Gays" PrEP study were prospectively enrolled. Anal, penile, and oral samples were collected at baseline and every 6 months for HPV detection and genotyping. Anal swabs for cytology were obtained at baseline and at 24 months. RESULTS: We enrolled 162 participants. The prevalences of any HPV genotypes at baseline were 92%, 32%, and 12% at the anal, penile, and oral sites, respectively. High-risk (HR) HPV genotypes were observed in 84%, 25%, and 10% of anal, penile, and oral baseline samples, respectively. Nonavalent HPV vaccine genotypes were observed in 77%, 22%, and 6% of anal, penile, and oral baseline samples, respectively. Multiple infections were observed in 76%, 17%, and 3% of cases at the anal, penile, and oral sites, respectively. The most frequent HR genotypes were HPV 53, 51, and 16 in anal samples; HPV 33, 39, and 73 in penile samples; and HPV 66 in oral samples. The incidence of any HPV genotype at the anal site was 86.2/1000 person-months and the incidence of HR-HPV genotypes was 72.3/1000 person-months. The baseline cytology was normal in 32% of cases and was classified as atypical squamous cells of undetermined significance, low-grade squamous intra-epithelial lesion, high-grade squamous intra-epithelial lesion (HSIL), and atypical squamous cells that cannot exclude HSIL in 23%, 40%, 5%, and 1% of cases, respectively. CONCLUSIONS: PrEP users have a similar risk of HPV infection as MSM living with HIV and the risk is much higher than that previously reported in MSM living without HIV.

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.

Coverage of Sex Acts by Event-Driven Pre-exposure Prophylaxis: A Sub-Study of the ANRS IPERGAY Trial.

We assessed the coverage of sex acts by event-driven pre-exposure prophylaxis (ED-PrEP) over a 2-month period in 54 participants in the open label phase of the ANRS Ipergay trial. Participants received an electronic monitoring system device to record bottle openings. Self-questionnaires collected daily information on PrEP intake and sexual behavior. Intake was also estimated through returned pill counts. Full coverage of sex acts was defined as at least one pill taken both within 24 h before and within 48 h following sex. There was a strong correlation (r = - 0.92) between the number of bottle openings and returned pill counts. During the study, 42 participants (78%) practiced ED-PrEP and 12 (22%) daily PrEP with bottle openings at least 5 days/week whatever their sexual activity. Out of the 154 reported receptive anal sex acts, 81% were condomless: among them, PrEP coverage was hight: 97% among those practicing daily PrEP and 82% among those using ED-PrEP.

On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.

BACKGROUND: Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen. METHODS: We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections. RESULTS: Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03). CONCLUSIONS: The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events. (Funded by the National Agency of Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT01473472.).

Factors associated with partner notification of STIs in men who have sex with men on PrEP in France: a cross-sectional substudy of the ANRS-IPERGAY trial.

OBJECTIVES: Partner notification (PN) is a useful public health approach to enhance targeted testing of people at high risk of HIV and other STIs, and subsequent linkage to care for those diagnosed. In France, no specific PN guidelines exist and information about current practices is scarce. We used the ANRS-IPERGAY PrEP trial to investigate PN in HIV-negative men who have sex with men (MSM) reporting a bacterial STI. METHODS: This substudy included 275 participants who completed a specific online PN questionnaire during the open-label extension study of the ANRS-Intervention Préventive de l'Exposition aux Risques avec et pour les Gays (IPERGAY) trial. Variables used as proxies of at-risk practices were defined using data collected at the previous follow-up visit about participants' most recent sexual encounter and preventive behaviours. χ2 or Fisher's exact test helped select variables eligible for multiple logistic models. RESULTS: Of the 275 participants, 250 reported at least one previous STI. Among the latter, 172 (68.8%) had informed their partner(s) of their most recent STI. Of these, 138 (80.2%) and 83 (48.3%) had notified their casual and main partners, respectively. Participants were less likely to notify their main partner when their most recent sexual encounter involved unsafe anal sex with a casual partner (adjusted OR (aOR) (95% CI) 0.18 (0.06 to 0.54), P=0.02). Older participants were less likely to inform casual partners (aOR (95% CI) 0.44 (0.21 to 0.94), P=0.03), while those practising chemsex during their most recent sexual encounter were more likely to inform their casual partners (aOR (95% CI) 2.56 (1.07 to 6.09), P=0.03). CONCLUSION: Unsafe sexual encounters with people other than main partners and street drugs use were two sociobehavioural factors identified, respectively, as a barrier to main PN and a motivator for casual PN, in a sample of high-risk MSM. These results provide an insight into current PN practices regarding STI in France and might inform future decisions about how to define feasible and acceptable PN programmes.

Assessment of HIV Screening Tests for Use in Preexposure Prophylaxis Programs.

Preexposure prophylaxis programs involve frequent human immunodeficiency virus (HIV) testing. We evaluated the sensitivity of 2 antigen/antibody immunoassays (Architect and Bioplex), 2 antibody-based rapid tests (Vikia-HIV-1/2 and Autotest-VIH), and 1 antigen/antibody rapid test (Alere HIV Combo) for the diagnosis of HIV infection. Among the 31 HIV-1-infected participants in the ANRS-IPERGAY trial, HIV-1 RNA was detected alone in only 2. The sensitivities of the Architect and Bioplex assays were 83% (95% confidence interval [CI], 76%-99%) and 82% (95% CI, 63%-94%), respectively. The sensitivities of the Vikia, Autotest, and Alere tests were 54% (95% CI, 34%-72%), 50% (95% CI, 31%-69%), and 78% (95% CI, 58%-91%), respectively. Antigen/antibody tests should be preferred to avoid missing cases of acute HIV infection and to decrease the related risks of viral transmission and emergence of drug resistance.

Single-dose pharmacokinetics and pharmacodynamics of oral tenofovir and emtricitabine in blood, saliva and rectal tissue: a sub-study of the ANRS IPERGAY trial.

OBJECTIVES: In the ANRS IPERGAY pre-exposure prophylaxis (PrEP) trial, a single dose of tenofovir disoproxil fumarate and emtricitabine was taken orally 2-24 h before sexual intercourse. A sub-study was conducted to assess the pharmacokinetics of tenofovir and emtricitabine in blood, saliva and rectal tissue following this initial oral intake. METHODS: Plasma, PBMC, saliva and rectal tissue sampling was performed over 24 h in 12 seronegative men before enrolment in the ANRS IPERGAY trial, following a single dose of 600 mg tenofovir disoproxil fumarate/400 mg emtricitabine. Ex vivo HIV infectibility of rectal biopsies was also assessed. RESULTS: The median plasma Tmax of tenofovir (median Cmax: 401 µg/L) and emtricitabine (median Cmax: 2868 µg/L) was obtained 1 h (range: 0.5-4) and 2 h (range: 1-4) after dosing, respectively. The median C24 of tenofovir and emtricitabine was 40 and 63 µg/L, respectively. The median PBMC tenofovir diphosphate and emtricitabine triphosphate levels were 12.2 and 16.7 fmol/106 cells and 2800 and 2000 fmol/106 cells at 2 and 24 h after dosing, respectively. Saliva/plasma AUC0-24 ratios were 2% and 17% for tenofovir and emtricitabine, respectively. Emtricitabine was detected in rectal tissue 30 min after dosing, whereas tenofovir was only detectable at 24 h. Ex vivo HIV infectibility assays of rectal biopsies showed partial protection after dosing (P < 0.07). DISCUSSION: A single high dose of oral tenofovir disoproxil fumarate/emtricitabine provides rapid and high blood levels of tenofovir and emtricitabine, with rapid diffusion of emtricitabine in saliva and rectal tissue.

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

The 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 among participants 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 follow-up. 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.

Acceptability of an "on-demand" pre-exposure HIV prophylaxis trial among men who have sex with men living in France.

Although predictors of willingness to take daily, self-administered pre-exposure HIV prophylaxis (PrEP) for men who have sex with men (MSM) have been studied in the context of several PrEP trials internationally, little is known about MSM interested in participating in a trial on the use of PrEP on an "on -demand" basis, i.e., taking a first dose of combined tenofovir/emtricitabine a few hours before possible HIV sexual exposure and a second dose a few hours afterwards. A double-blind placebo randomized PrEP trial will soon begin in France to evaluate the effectiveness of PrEP in terms of reducing HIV infection rates, among MSM self-administering "on-demand" PrEP. To assess potential participants' characteristics associated with willingness to participate in the trial and identify barriers and facilitators to implementation, MSM completed a self-administered questionnaire, distributed via gay venues and community websites. Among the 443 respondents who reported being HIV-negative, 40% reported being interested in participating. Factors independently associated with interest included: reporting lower educational level, more than 20 male sexual partners in the previous year, reporting unprotected anal sex with casual partners and preferring PrEP follow-up visits in a devoted area within a hospital. There is great interest in participating in a future "on-demand" PrEP trial among HIV-negative MSM and particularly in those at potentially high risk of HIV exposure. Providing confidentiality and tailored counseling during PrEP follow-up are important issues.

Maternal immune response and neonatal seroprotection from a single dose of a monovalent nonadjuvanted 2009 influenza A(H1N1) vaccine: a single-group trial.

BACKGROUND: Pregnant women and infants who get influenza are at increased risk for severe illness. OBJECTIVE: To evaluate the immunogenicity and transplacental antibody transfer of 2009 pandemic influenza A(H1N1) vaccine administered during pregnancy. DESIGN: Prospective, multicenter, single-group clinical trial. (ClinicalTrials.gov registration number: NCT01024400) SETTING: Five level-3 perinatal centers in France. PATIENTS: 107 pregnant women between 22(0/7) and 32(0/7) weeks of gestation. INTERVENTION: An intramuscular dose of a nonadjuvanted H1N1 vaccine that contained 15 mcg of hemagglutinin. MEASUREMENTS: Proportion of women with an influenza antibody titer of 1:40 or greater at days 21 and 42 after vaccination, delivery, and 3 months after delivery. Seroconversion rate, fold increase in the geometric mean titer 21 days after vaccination, and proportion of neonates with an antibody titer of 1:40 or greater at birth were also assessed. RESULTS: At baseline, 19% of the women had an antibody titer of 1:40 or greater. At day 21, 98% of the women had an antibody titer of 1:40 or greater, the seroconversion rate was 93%, and the fold increase in geometric mean titer was 67.4. At day 42, delivery, and 3 months after delivery, 98%, 92%, and 90% of the women, respectively, had an antibody titer of 1:40 or greater. Ninety-five percent of the cord serum samples obtained from 88 neonates showed an antibody titer of 1:40 or greater. The median neonate-mother antibody titer ratio was 1.4. LIMITATIONS: Only healthy pregnant women were selected. Data on hemagglutination inhibition antibody titers of infants were reported only at birth. CONCLUSION: A single dose of a nonadjuvanted influenza A(H1N1) vaccine with 15 mcg of hemagglutinin triggered a strong immune response in pregnant women and a high rate of neonatal seroprotection. PRIMARY FUNDING SOURCE: French National Institute of Health and Medical Research.

Incidence and risk factors for recurrent sexually transmitted infections among MSM on HIV pre-exposure prophylaxis.

OBJECTIVE: High rates of sexually transmitted infections (STIs) have been reported among pre-exposure prophylaxis (PrEP) users. We wished to assess the incidence and risk factors for recurrent STIs. DESIGN: The ANRS IPERGAY trial was a prospective study investigating PrEP among MSM and transgender women in outpatient clinics in France and Canada. In all, 429 participants were enrolled, offered up to 4 years of PrEP and screened for bacterial STIs (syphilis, chlamydia and gonorrhea) at baseline and every 6 months. METHODS: STIs incidence was calculated yearly. Cox proportional hazards model regression was used to explore associations between participants characteristics at baseline and recurrent STI during follow-up. RESULTS: Over a median follow-up of 23 months, bacterial STI incidence was 75, 33, 13, 32 and 30 per 100 person-years for all STIs, rectal STIs, syphilis, gonorrhea and chlamydia, respectively. STI incidence significantly increased from the first year to the fourth year of the study (55 vs. 90 per 100 person-years, P  < 0.001). During the study period, 167 participants (39%) presented with more than one bacterial STIs which accounted for 86% of all STIs. Baseline risk factors associated with recurrent STIs in a multivariate analysis were an STI at baseline [hazards ratio: 1.48 (95% confidence interval (CI): 1.06-2.07), P  = 0.02], more than eight sexual partners in prior 2 months [hazards ratio: 1.72 (95% CI: 1.21-2.43), P  = 0.002] and the use of gamma-hydroxybutyrate [hazards ratio: 1.66 (95% CI: 1.16-2.38), P  = 0.005]. CONCLUSION: STI incidence was high and increased over time. Most STIs were concentrated in a high-risk group that should be targeted for future interventions.

Evaluation of Drug Abuse by Hair Analysis and Self-Reported Use Among MSM Under PrEP: Results From a French Substudy of the ANRS-IPERGAY Trial.

BACKGROUND: We used the Agence nationale de Recherches sur le sida et les hépatites virales (ANRS)-IPERGAY trial to qualitatively and quantitatively measure drug use among men who have sex with men under preexposure prophylaxis using 2 different methods, to better understand and collectively respond to risky practices. METHOD: We included 69 volunteers of the ANRS-IPERGAY trial. We measured drug use by 2 methods: (1) drug detection by hair analysis and (2) reported drug use by self-reported drug consumption. RESULTS: New psychoactive substances (NPS) and conventional drugs were detected in 53 of the 69 (77%) volunteers by hair analysis and in 39 of the 69 (57%) volunteers by questionnaires. On the 219 hair segments analyzed, the most commonly used drugs were cocaine in 47 of the 69 (68%), 3,4-methylenedioxymethamphetamine/ecstasy in 31 of the 69 (45%), and NPS in 27 of the 69 (39%). On the 1061 collected questionnaires, the most commonly used drugs were cocaine in 31 of the 69 (45%), 3,4-methylenedioxymethamphetamine/ecstasy in 29 of the 69 (42%), and NPS in 16 of the 69 (23%). Hair analysis detects more conventional drugs and/or NPS use (P < 0.05). Drug use identified by hair was significantly associated with a higher number of sexual partners in the past 2 months (P ≤ 0.001), more often casual partners (P ≤ 0.001), condomless anal sex (P ≤ 0.005), hardcore sexual practices (P ≤ 0.001), a higher number of sexually transmitted infections, and chemsex (P ≤ 0.05). CONCLUSIONS: Self-report drug use by questionnaires remains the reference tool for harm reduction at the individual level because of its feasibility and low cost. However, hair analysis is more sensitive, objectively assessing consumption, and interesting to understand uses and to be able to collectively respond to risky practices with adapted messages.

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 kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate - emtricitabine for HIV pre-exposure prophylaxis.

INTRODUCTION: Daily pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is associated with a small but statistically significant decrease in estimated glomerular filtration rate (eGFR). We assessed the renal safety of on-demand PrEP with TDF/FTC in HIV-1 uninfected men. METHODS: We used data from the randomized double-blind placebo-controlled ANRS-IPERGAY trial and its open-label extension conducted between February 2012 and June 2016 among HIV-uninfected MSM starting on-demand PrEP. Using linear mixed model, we evaluated the mean eGFR decline from baseline over time and determined risks factors associated with eGFR decline during the study. RESULTS: During the blind phase, with a median follow-up of 9.4 months, the mean decline slope of eGFR from baseline was -0.88 and -1.53 mL/min/1.73 m2 per year in the placebo (n = 201) and the TDF/FTC group (n = 198) respectively, with a slope difference of 0.65 mL/min/1.73 m2 per year (p = 0.27). Including both phases, 389 participants started on-demand TDF/FTC with a median follow-up of 19.2 months and a mean decline of eGFR from baseline of -1.14 mL/min/1.73 m2 per year (p < 0.001). The slope of eGFR reduction was not significantly different in participants with baseline eGFR ≤ 90 mL/min/1.73 m2 (p = 0.44), age >40 years (p = 0.24) or hypertension (p = 0.21). There was a dose-response relationship between recent tenofovir exposure and lower eGFR when considering the number of pills taken in the two months prior the visit (eGFR difference of -0.88 mL/min/1.73 m2 between >15 pills/month vs. ≤15 pills/month, p < 0.01) or plasma tenofovir concentrations at the visit (eGFR difference compared to ≤2 ng/mL: >2 to ≤10ng/mL: -0.98 mL/min/1.73 m2 , >10 to ≤40ng/mL: -1.28 mL/min/1.73 m2 , >40 ng/mL: -1.82 mL/min/1.73 m2 , p < 0.001). Three participants discontinued TDF/FTC for eGFR < 60 mL/min/1.73 m2 during the OLE phase. No case of Fanconi syndrome was reported. CONCLUSIONS: The renal safety of on-demand PrEP with TDF/FTC was good. The overall reduction and intermittent exposure to TDF/FTC may explain this good renal safety.

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.

BACKGROUND: 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. 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.

Efficacy and safety of ritonavir-boosted dual protease inhibitor therapy in antiretroviral-naive HIV-1-infected patients: the 2IP ANRS 127 study.

OBJECTIVES: We evaluate the efficacy and tolerability of ritonavir-boosted dual protease inhibitor as a nucleoside reverse transcriptase inhibitor-sparing regimen in a prospective open-label randomized pilot trial in antiretroviral-naive patients. METHODS: Thirty patients received fosamprenavir/atazanavir/ritonavir (Group 1) and 31 patients received saquinavir/atazanavir/ritonavir (Group 2). The primary endpoint for efficacy was the rate of early virological success, defined as plasma viral load <50 copies/mL at week 16. The study is registered with ClinicalTrials.gov (NCT00122603). RESULTS: At baseline, median (range) viral load was 4.8 log(10) copies/mL (4.0-5.7) and the median CD4 cell count was 271/mm(3) (197-740). Viral load was <50 copies/mL in 12/30 patients [40%, 95% confidence interval (CI) 23%-58%] and 13/31 patients (42%, 95% CI 25%-59%) at week 16 in Groups 1 and 2, respectively. Patients with failing regimens (viral load >or=400 copies/mL at week 16 or >or=50 copies/mL at week 24) were switched to a standard antiretroviral regimen. At week 48, by an intention-to-treat analysis, 23/30 patients (77%) and 26/31 patients (84%) had plasma HIV-1 RNA <50 copies/mL in Groups 1 and 2, respectively. Four patients discontinued treatment for adverse events, all before week 4. No major changes in the protease gene were detected at treatment failure relative to baseline. Baseline viral load <50 000 copies/mL was the only predictor of virological success at week 16. CONCLUSIONS: Ritonavir-boosted dual protease inhibitor regimens targeting only one step of viral replication were insufficient to rapidly suppress plasma HIV RNA to <50 copies/mL in antiretroviral-naive patients with high viral load at baseline.

In-depth Sampling of High-risk Populations to Characterize HIV Transmission Epidemics Among Young MSM Using PrEP in France and Quebec.

BACKGROUND: A better understanding of HIV transmission dynamics among populations at high risk is important for development of prevention strategies. We determined HIV transmission networks from infected individuals enrolled in the pre-exposure prophylaxis (PrEP) IPERGAY trial in combination with the ANRS PRIMO and Montreal PHI cohorts to identify and characterize active clusters of transmission in this high-risk population. METHODS: Genotypic resistance tests were performed on plasma samples from 31 IPERGAY participants. Reverse transcriptase sequences were analyzed in combination with unique HIV pol sequences from 1351 individuals enrolled in the PRIMO ANRS cohort (1999-2014) and 511 individuals enrolled in the Montreal PHI cohort (1996-2016). Network analyses were performed to infer putative relationships between all participants. RESULTS: Overall, 1893 participants were included. Transmission network analyses revealed that 14 individuals (45.2%) from the IPERGAY trial were involved in 13 clusters sampled over a median period (interquartile range) of 2 (0.3-7.8) years, including 7 dyads and 6 larger clusters ranging from 4 to 28 individuals. When comparing characteristics between clustering individuals enrolled in the PRIMO cohort (n = 377) and in IPERGAY (n = 14), we found that IPERGAY participants had a higher viral load (5.93 vs 5.20 log10 copies/mL, P = .032) and reported a higher number of partners in the last 2 months (P < .01). CONCLUSIONS: These results demonstrate high rates of HIV transmission clustering among young high-risk MSM enrolled in the IPERGAY trial. In-depth sampling of high-risk populations may help to uncover unobserved transmission intermediaries and improve prevention efforts that could be targeted to the most active clusters.

Is on-Demand HIV Pre-exposure Prophylaxis a Suitable Tool for Men Who Have Sex With Men Who Practice Chemsex? Results From a Substudy of the ANRS-IPERGAY Trial.

BACKGROUND: Chemsex-the use of psychoactive substances during sexual encounters-among men who have sex with men is a growing concern. On-demand HIV pre-exposure prophylaxis (PrEP) may be a suitable tool to prevent HIV transmission among "chemsexers." We used the open-label extension study of the ANRS-IPERGAY trial to describe chemsexers and their PrEP use. METHODS: Among the 361 men who have sex with men enrolled in ANRS-IPERGAY's open-label extension study, we selected the 331 with available data on drug use. A 2-monthly web questionnaire on sociobehavioral data was used to compare sexual behaviors between questionnaires where chemsex was reported and those where it was not. Using a generalized estimating equation logistic regression, we studied whether practicing chemsex was associated with correct PrEP use. RESULTS: Among the 331 participants, 30% reported chemsex practice at least once during follow-up and were considered chemsexers. Chemsex was reported in 16% of all questionnaires. Chemsexers were not significantly different from nonchemsexers regarding sociodemographic characteristics, although they reported greater use of anxiolytics and more sensation-seeking. Reporting chemsex was associated with more high-risk sexual practices and a higher perception of risk. After adjustment for other potential correlates, chemsex remained associated with correct PrEP use [odds ratio (95% confidence interval) = 2.24 (1.37 to 3.66)]. CONCLUSIONS: Our findings show that chemsexers were more likely to report high-risk sexual practices but also had a higher perception of risk. They were also more likely to use PrEP correctly when practicing chemsex. Consequently, PrEP may be a suitable tool to reduce HIV-risk transmission among chemsexers.