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Risk factors for cytomegalovirus (CMV) acquisition in men having sex with men remain unclear. Seroprevalence, incidence, risk factors and shedding of CMV were analyzed among participants enrolled in the HIV pre-exposure prophylaxis IPERGAY-ANRS trial. Among the 417 participants tested, 382 were seropositive at baseline (prevalence of 91.6%; 95%CI[88.5–94.1]) and 10/35 seroconverted during the study (incidence of 17.1 per 100 person-years; 95%CI[8.2–31.3]). A high number of sexual partners was independently associated with CMV seroprevalence. Shedding among CMV-seroconverters was reported for 6/9 and 2/9 at the oral and anal levels, respectively. Our data supports transmission of CMV during sexual contacts. Study part of the ANRS-IPERGAY Clinical trial ClinicalTrials.gov number, NCT01473472. [ABSTRACT FROM AUTHOR]

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 [m.sup.2] 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 [m.sup.2] 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 [m.sup.2] per year (p < 0.001). The slope of eGFR reduction was not significantly different in participants with baseline eGFR [less than or equal to] 90 mL/min/1.73 [m.sup.2] (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 [m.sup.2] between >15 pills/month vs. [less than or equal to]15 pills/month, p < 0.01) or plasma tenofovir concentrations at the visit (eGFR difference compared to [less than or equal to]2 ng/mL: >2 to [less than or equal to]10ng/mL: -0.98 mL/min/1.73 [m.sup.2], >10 to [less than or equal to]40ng/mL: -1.28 mL/min/1.73 [m.sup.2], >40 ng/mL: -1.82 mL/min/1.73 [m.sup.2], p < 0.001). Three participants discontinued TDF/FTC for eGFR < 60 mL/min/1.73 [m.sup.2] 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. Keywords: PrEP; on-demand; intermittent; kidney; eGFR; tenofovir; HIV, 1 | INTRODUCTION Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)--emtricitabine (FTC) raises a lot of expectations to hamper HIV epidemic due to its high effectiveness to prevent HIV acquisition [...]

Objectives: We aimed to assess among men who have sex with men (MSM) risk factors for HIV infection, to identify those who require urgent pre-exposure prophylaxis (PrEP) prescription.Methods: All participants enrolled in the placebo arm of the ANRS IPERGAY trial, or infected between screening and day 0, were included. Baseline characteristics were described and HIV incidence rate ratios (RRs) were estimated with their 95% CIs.Results: 203 MSM were included with a median follow-up of 9 months. During the study period, 16 participants acquired HIV infection while not receiving tenofovir disoproxil and emtricitabin (TDF/FTC) over 212.4 person-years (PYs) of follow-up (incidence rate 7.5/100 PYs, 95% CI: 4.3 to 12.2). Being enrolled in Paris was associated with a significant increased risk of HIV infection (RR: 4.1; 95% CI: 1.1 to 28.3). A high number of sexual partners in prior 2 months (≥10 vs <5) and of condomless receptive anal sex episodes in prior 12 months (>5 vs <5) were strong predictors for HIV acquisition (RR: 10.6 (2 to 260.2) and 3.3 (1.2 to 10.2), respectively). Those who reported more often or only receptive sexual practices were also at increased risk (RR: 9.8 (2.0 to 246.6)). The use of recreational drugs in prior 12 months, especially gamma hydroxybutarate/gamma butyrolactone (RR: 5.9; 95% CI: 2 to 21.7), was associated with a significantly increased risk of HIV acquisition even after adjustment for sexual practices.Conclusions: MSM who have frequent condomless receptive anal sex and multiple partners, or use recreational drugs should be targeted in priority for PrEP prescription especially if they live in an area with a high prevalence of HIV infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is a reliable pharmacokinetics biomarker of adherence to tenofovir disoproxil fumarate (TDF). We aimed to use DBSs to estimate pill intake among participants using on-demand pre-exposure prophylaxis (PrEP) and to identify predictive factors associated with higher TFV-DP concentrations.Methods: DBSs were collected at the last study visit of the open-label phase of the ANRS IPERGAY study, assessing on-demand oral TDF/emtricitabine for PrEP among MSM and transgender female participants. We quantified TFV-DP in DBSs centrally. We assessed correlation between pill count and TFV-DP concentration by Spearman correlation and explored associations between participant demographics, sexual behaviour and PrEP use during sexual intercourse (SI) with TFV-DP concentrations by univariate and multivariate logistic regression models.Results: The median age of the 245 participants included in this study was 40 years, with a median body weight of 73 kg. Median (IQR) TFV-DP concentration reached 517 (128-868) fmol/punch, corresponding to an estimated intake of 8-12 tablets per month (2-3 doses per week). Only 39% of participants had a TFV-DP concentration above 700 fmol/punch. TFV-DP concentrations were moderately correlated with pill count (r: 0.59; P < 0.001). In multivariate analysis, only systematic use of PrEP during SI and more frequent episodes of SI in the past 4 weeks were significantly associated with higher TFV-DP levels [OR (95% CI): 11.30 (3.62-35.33) and 1.46 (1.19-1.79), respectively; P < 0.001].Conclusions: Among participants using on-demand PrEP, estimated pill intake reached 8-12 tablets per month and was correlated with frequency and systematic use of PrEP for SI. [ABSTRACT FROM AUTHOR]

Introduction: In the SMART trial, baseline plasma hsCRP, IL6 and D‐dimer levels were strongly correlated to all‐cause mortality. A case‐control study has shown an increase of IL‐6 and D‐dimer levels after one month of antiretroviral therapy (ART) interruption, which was correlated to viral load. Restarting ART was associated to a decrease in D‐dimer but not IL‐6 or hsCRP levels. We assessed biomarkers levels up to 96 weeks in ART‐experienced adults with plasma HIV RNA levels Methods: Stored plasma for 160 participants (80 IT and 80 CT), matched by age, sex and CDC classification, were analyzed blinded for IL‐6, sCD‐14, hsCRP and D‐dimer levels at baseline, week 8 (IT group only), week 16 and week 96. Lower levels of detection for IL‐6, sCD14, hsCRP and D‐Dimer were 1.5 pg/mL, 250 ng/mL, 0.03 µg/mL and 0.21 µg/mL, respectively. The primary objective was to compare changes in IL‐6, hsCRP, sCD14 and D‐dimer plasma levels from baseline to week 8, 16 and 96 in the IT and CT arms. Biomarkers levels were log10 transformed prior to analysis. Results: At baseline, patients were mostly men (86%), with a median age of 40 years, a CD4+ T‐cell count of 768/mm[sup.3], have received a median of 4.7 years of ART and 85% had HIV RNA Compared to baseline, D‐dimer levels significantly increased 8 weeks after ART interruption in the IT arm (+23% fold change, 95% CI +9% to +39%) but reverted to baseline levels at week 16 and remained unchanged at week 96. There was no significant change from baseline in the other biomarker levels in the IT arm. Similarly, no significant change from baseline in biomarker levels was seen in the CT arm up to 96 weeks. Conclusion: Coagulation and inflammatory biomarkers levels remained stable over 96 weeks in well‐suppressed HIV‐infected patient on ART. Following ART interruption there was a significant increase in D‐dimer but not in inflammatory biomarkers levels. This increase was reversed upon reintroduction of ART. These data suggest that ART interruption increases coagulation rather than inflammatory biomarkers., Table 1: Changes in biomarkers levels in participants from the intermittent (IT) vs continuous (CT) treatment arms through 96 weeks (*p=0.002, Wilcoxon test) IL‐6(pg/mL) sCD14(ng/mL) hsCRP(#x00B5;g/mL) D‐dimer(µg/mL) IT CT IT [...]

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. [ABSTRACT FROM AUTHOR]

Background: In the ANRS EASIER trial where treatment-experienced patients switched from enfuvirtide (ENF) to raltegravir (RAL), a high incidence of transaminase elevation was reported in the RAL arm. Methods: We compared the incidence of emergent liver enzyme elevations (LEE) of grade 2 or more among patients randomized to the maintenance ENF arm or the switch RAL arm up to W24. We also assessed the overall incidence of LEE over the 48-week duration of the trial and baseline risk factors for grade 2 or more alanine aminotransferase (ALT) elevation using univariate and multivariate analyses. Results: During the first 24 weeks, 6/84 (7.1 %) and 2/85 patients (2.4%) presented with ALT elevation of grade 2 or more in the RAL and ENF arms, respectively (p = 0.21). Grade 2 or more γGT and ALP elevations were seen in 18 and 11 % (p = 0.35), and 5 and 1 % (p = 0.14) of patients in the RAL and ENF arms, respectively. The 48-week incidence of grade 2 or more LEE was 11.6 per 100-pts-years for ALT, 24.5 per 100-pts-years for γ-GT and 4.5 per 100-pts-years for ALP, respectively. In the multivariate analysis, tipranavir/ritonavir use (OR 3.66; 95 % Cl [1.20-11.1], p = 0.022) and elevated ALT at baseline (OR 10.3; 95 % Cl [2.67-39.6], p < 10-3) were significantly associated with a grade 2 or more ALT elevation during follow-up. Conclusion: The incidence of LEE was relatively high in these highly treatment-experienced patients switching to a RAL-based regimen. Both tipranavir/ritonavir use and high baseline ALT levels were associated with an increased risk of ALT. [ABSTRACT FROM AUTHOR]