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Objectives: Our objective was to identify missed opportunities for the use of pre-exposure prophylaxis (PrEP) in people with recently acquired HIV, factors associated with PrEP knowledge, and reasons for not using PrEP., Design: This was a French national cross-sectional multicentre study enrolling people diagnosed with recent HIV (incomplete Western blot or negative HIV test in the previous 6 months) in 28 HIV clinical centres. Data were gathered using a self-administered questionnaire (SAQ)., Method: We analysed missed opportunities for PrEP use via a retrospective prep cascade. Factors associated with prior knowledge of PrEP and reasons for PrEP non-use among those who knew about PrEP were described using univariate and multivariate logistic regression models., Results: Of the 224 eligible patients, 185 completed the SAQ and 168 (91%) were eligible for PrEP. Of these, 90% reported seeing at least one physician during the previous year, 26% received information about PrEP, and 5% used PrEP. Factors independently associated with a higher probability of knowing about PrEP were being a man who has sex with men, being aged 25-30 years (vs older), undergoing HIV screening at least once every semester (vs less often; odds ratio [OR] 4.11; 95% confidence interval [CI] 2.00-8.45), and practicing chemsex (OR 3.19; 95% CI 1.12-9.10). Fear of side effects and a low perceived risk of HIV infection were the two most common reasons for not using PrEP (N = 40 [33.33%] and N = 34 [28.3%], respectively)., Conclusions: We found two gaps in the retrospective PrEP cascade: insufficient provision of PrEP information by healthcare providers (mainly general practitioners) and low PrEP acceptability by informed, eligible patients. More diverse healthcare providers need to be involved in PrEP prescription, and at-risk people need to be sensitized to the risk of HIV infection., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: In the past years, we observed a sharp increase of Syphilis, especially among male who have sex with male (MSM), either HIV-infected, or on pre-exposure prophylaxis (PrEP). Our aim was to assess syphilis prevalence and incidence among people living with HIV (PLWH) and PrEP users., Methods: PLWH were included from 2010 to 2020 and PrEP users from 2016 to 2020 from the Dat'AIDS French cohort. We calculated syphilis prevalence and incidences for first infections, re-infections, and iterative infections (> 2 times). T-Tests, Wilcoxon tests and Chi2 test were used for descriptive analysis and multivariate logistic regression models were used to estimate Odds ratios (OR) and 95% confidence intervals (95% CI) for factors associated with syphilis., Results: Among the 8 583 PLWH, prevalence of subject with past or present syphilis was 19.9%. These subjects were more likely MSM or transgender and aged over 35 years, but prevalence was lower in AIDS subjects. Same pattern was seen for incident infection and re-infection. Incidence was 3.8 per 100 person-years for infection and 6.5 per 100 person-years for re-infection. Among 1 680 PrEP users, syphilis prevalence was 25.8%, with an estimated 7.2% frequency of active syphilis. Risk of syphilis infection was higher in male and increased with age. Incidence was 11.2 per 100 person-years for infection and 11.1 per 100 person-years for re-infection., Conclusion: Syphilis prevalence and incidence were high, especially in older MSM with controlled HIV infection and PrEP users, enhancing the need to improve syphilis screening and behavioral risk reduction counseling among high-risk subjects., Competing Interests: D. Rey declared having received grants from ViiV Healthcare (expert board participation and fee for lecture) and Mylan (fee for lecture). C. Allavena declared having received grants from Gilead, Janssen, MSD, ViiV Healthcare. L. Cotte declared having received grants from Abbvie, Gilead Science, Janssen Cilag, MSD, ViiV Healthcare. For the remaining authors no other conflicts of interest were declared.

Objectives and Methods: : Progressive multifocal leukoencephalopathy (PML) has rarely been reported in people with HIV (PWH) with long-term HIV immune-virological control. We describe the clinical and biological characteristics of patients with confirmed PML among PWH with a CD4+ cell count more than 200 cells/μl and an undetectable HIV RNA viral load after at least 6 months of combined antiretroviral therapy (cART) at the time of PML diagnosis, in the large French multicenter Dat'AIDS cohort., Results: : Among 571 diagnoses of PML reported in the Dat'AIDS cohort between 2000 and 2019, 10 cases (1.75%) occurred in PWH with a CD4+ cell count greater than 200 cells/μl and an undetectable HIV RNA viral load after at least 6 months of cART. Median CD4+ cell count at PML diagnosis was 395 cells/μl (IQR 310-477). The median duration between the last detectable HIV viral load and the PML diagnosis was 41.1 months (IQR 8.2-67.4). Only one patient treated with rituximab-based chemotherapy for a large B-cell lymphoma had an established risk factor for PML. Among the nine other patients with no apparent severe immunodeficiency, multiple factors of impaired immunity could have led to the development of PML: hepatitis C virus (HCV) co-infection (n = 6), cirrhosis (n = 4), HHV-8 co-infection (n = 3) with Kaposi's sarcoma (n = 2) in association with Castleman's disease (n = 1) and indolent IgA multiple myeloma (n = 1)., Conclusion: : This study highlights that factors other than low CD4+ cell count and high HIV viral load may be associated with the occurrence of PML. Further studies are warranted to investigate in greater detail the immunologic characteristics of PWH with immune-virological control who develop PML., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The arrival of highly effective, well-tolerated, direct-acting antiviral agents (DAA) led to a dramatic decrease in hepatitis C virus (HCV) prevalence. Human immunodeficiency virus (HIV)-HCV-coinfected patients are deemed a priority population for HCV elimination, while a rise in recently acquired HCV infections in men who have sex with men (MSM) has been described. We describe the variations in HIV-HCV epidemiology in the French Dat'AIDS cohort., Methods: This was a retrospective analysis of a prospective cohort of persons living with HIV (PLWH) from 2012 to 2018. We determined HCV prevalence, HCV incidence, proportion of viremic patients, treatment uptake, and mortality rate in the full cohort and by HIV risk factors., Results: From 2012 to 2018, 50 861 PLWH with a known HCV status were followed up. During the period, HCV prevalence decreased from 15.4% to 13.5%. HCV prevalence among new HIV cases increased from 1.9% to 3.5% in MSM but remained stable in other groups. Recently acquired HCV incidence increased from 0.36/100 person-years to 1.25/100 person-years in MSM. The proportion of viremic patients decreased from 67.0% to 8.9%. MSM became the first group of viremic patients in 2018 (37.9%). Recently acquired hepatitis represented 59.2% of viremic MSM in 2018. DAA treatment uptake increased from 11.4% to 61.5%. More treatments were initiated in MSM in 2018 (41.2%) than in intravenous drug users (35.6%). In MSM, treatment at the acute phase represented 30.0% of treatments in 2018., Conclusions: A major shift in HCV epidemiology was observed in PLWH in France from 2012 to 2018, leading to a unique situation in which the major group of HCV transmission in 2018 was MSM. Clinical Trials Registration. NCT02898987., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: As trends in new HIV diagnoses represent a measure of the HIV epidemic, we conducted a 6-year longitudinal study to evaluate the change in rates of new HIV diagnosis, stratified by birthplace, HIV risk groups and CD4 cell count at diagnosis in a large French multicentre cohort., Study Design: We performed a retrospective cohort study using data from the mainland French Dat'AIDS cohort., Methods: Data were obtained for subjects with a new HIV diagnosis date between 2013 and 2018. HIV diagnosis date was defined as the date of the first known positive HIV serology., Results: Between 2013 and 2018, a total of 68,376 people living with HIV (PLHIV) were followed in the Dat'AIDS cohort; 9543 persons were newly diagnosed with HIV. The annual number of new HIV diagnoses decreased from 1856 in 2013, to 1149 in 2018 (-38.1%), P = 0.01; it was more pronounced among subjects born in France, from 858 to 484 (-43.6%), P < 0.01, than in those born abroad (-23.8%, from 821 to 626, P = 0.13). Among subjects born in France, the decrease over the period was -46.7% among men who have sex with men (MSM), -43.5% for heterosexual women and -33.3% for heterosexual men., Conclusion: Our findings show changes in HIV epidemiology in PLHIV born in France, with a decline around 40% in new HIV diagnoses, and a more pronounced decrease among MSM and heterosexual women. Our results support the long-term effectiveness of the antiretroviral therapy as a prevention strategy among the various tools for HIV prevention., (Copyright © 2021 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objectives: Even in an 'optimal' health system, patients' characteristics may have an impact on their care. We investigated whether age, gender and place of birth have an impact in the HIV care continuum in France, a country with a universal free healthcare system., Methods: We estimated differences in the 5 year restricted mean percentage of person-time spent (i) in care, (ii) receiving ART and (iii) on ART and virally suppressed among 2432 (30.2%) women, 3925 MSM (48.7%) and 1709 men who have sex with women (MSW; 21.2%) entering care in the Dat'AIDS French prospective cohort between 1 January 2013 and 31 December 2017. Trial registration: Clinicaltrials.gov reference NCT02898987., Results: Men and women spent 85.6% and 82.8% of person-time on ART and 69.9% and 65% suppressed, respectively. MSM, MSW and women spent 86.9%, 82.6% and 82.8% of person-time on ART and 72.5%, 63.7% and 65% suppressed, respectively. Patients born in France (47%) and patients born abroad spent 87.9% and 81.9% of person-time on ART and 74.6% and 62.9% suppressed, respectively. Young men born abroad were found to spend the smallest person-time with non-detectable viral load (53% for MSW and 58.1% for MSM)., Conclusions: Despite free access to care and universal ART in France, disparities remain in the HIV continuum care across age, country of birth and way of HIV acquisition. Clinical and public health interventions targeting specific patients' conditions are needed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: J.-M.M. reports receiving financial support as an adviser for Gilead Sciences, Merck, Janssen, Bristol-Myers Squibb, and ViiV Healthcare, and research grants from Gilead Sciences and Merck. F.R. reports receiving financial support as an adviser for Gilead Sciences, Merck, Janssen, and ViiV Healthcare, and research grants from Gilead Sciences. B.S. reports receiving support as an adviser for Gilead Sciences, Merck, Janssen, and Bristol-Myers Squibb, and research grants from ANRS, Fondation Pierre Bergé, Gilead Sciences, and Merck. L.C. has received research grants from ViiV Healthcare and Merck, personal fees from Mylan, and nonfinancial support from BMS, Gilead Science, Janssen Cilag, MSD, and ViiV Healthcare. G.P. has received consulting fees from Bristol-Myers Squibb, Boehringer Ingelheim, Tibotec, Nephrotek, Gilead, Roche, MSD, Abbott, and ViiV Healthcare, and research grants from Bristol-Myers Squibb and Gilead Sciences. E.C. reports receiving financial support as an adviser for Janssen, Merck, ViiV, and Novartis, and nonfinancial support from Gilead Sciences. J.C. reports receiving financial support as an adviser for Gilead Sciences, Bristol-Myers Squibb, and AbbVie. L.M. reports receiving grants from ANRS, the Bill & Melinda Gates Foundation, and Gilead. G. Peytavin has received travel grants, consultancy fees, honoraria, or study grants from various pharmaceutical companies, including Gilead Sciences, Janssen, Merck, and ViiV Healthcare. The other authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: A new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) emerged in China during late 2019 and resulted in the coronavirus disease 2019 (COVID-19) pandemic which peaked in France in March-April 2020. Immunodeficiency, precariousness and promiscuity could increase the risk of COVID-19 in HIV-infected patients and in preexposure prophylaxis (PrEP) users. No epidemiological data are available in these two populations. We report COVID-19 attack rate in HIV-infected patients and in PrEP users in the Rhône department, France, and compared it with the general population., Design: Retrospective analysis of a laboratory database., Methods: COVID-19 testing strategy in France was centered on symptomatic infections, hospitalized patients and symptomatic healthcare workers while most asymptomatic cases were not confirmed. SARS-CoV-2 positivity rate on PCR assays and COVID-19 attack rate were determined in HIV-infected patients and in PrEP users. COVID-19 attack rate in the general population was estimated from health authorities' database and demographic data. A corrected attack rate taking into account the laboratory representativeness was calculated., Results: From March to April 2020, 24 860 samples from 19 113 patients (HIV-infected 77, PrEP users 27, others 19 009) were assessed for SARS-CoV-2 PCR assay. The positivity rate appeared similar in HIV-infected patients (15.6%), in PrEP users (14.8%) and in other patients (19.1%). The crude/corrected COVID-19 attack rate appeared similar in HIV-infected patients (0.31/0.38%) and in PrEP users (0.38/0.42%), and of the same order as the estimated attack rate in the general population (0.24%)., Conclusion: The risk of symptomatic COVID-19 in France appeared similar in HIV-infected patients and in PrEP users compared with the general population.

Objectives: Post-exposure prophylaxis (PEP) care remains a challenge for individuals with potential sexual exposure to HIV in terms of PEP completion and ongoing risk behaviours., Methods: A retrospective analysis was carried out on data from the French Dat'AIDS prevention cohort (NCT03795376) for individuals evaluated for PEP between 2004 and 2017. A multivariable analysis was performed of predictors of both PEP completion and condom use [odds ratios (ORs)] and their associated probabilities (P, with P > 95% being clinically relevant)., Results: Overall, 29 060 sexual exposures to HIV were evaluated for PEP [36% in men who have sex with men (MSM) and 64% in heterosexuals]. Overall, 12 different PEP regimens were offered in 19 240 cases (46%). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) was the preferred backbone (n = 14 304; 74%). We observed a shift from boosted protease inhibitor-based regimens to nonnucleoside reverse transcriptase inhibitor- or integrase inhibitor-based regimens in recent years. Overall, 20% of PEP prescriptions were prematurely discontinued. Older age, MSM, intercourse with a sex worker, rape and intercourse with a known HIV-infected source patient were factors associated with increased rates of PEP completion (OR > 1; P > 98%). None of the 12 PEP regimens was associated with premature discontinuation. We also found 12 774 cases of unprotected sexual intercourse (48%). Condom use decreased (OR < 1; P > 99%) with the year of exposure, and was lower in MSM and rape victims. Condom use increased (OR > 1, P > 99%) with age, and was higher in those who had intercourse with a sex worker or with a female partner and in those with knowledge of the partner's HIV status., Conclusions: We provide new insights into how rates of condom use and PEP completion might be improved in those receiving PEP by targeting certain groups of individuals for interventions. In particular, youth and MSM at risk should be linked in a prevention-to-care continuum., (© 2020 British HIV Association.)

Background: In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count., Methods: To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis., Results: During the study period, 61 822 patients were followed in the Dat'AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. The median delay between HIV diagnosis and cART initiation decreased from 9.07 (interquartile range [IQR], 1.39-33.47) months in 2007 to 0.77 (IQR, 0.37-1.60) months in 2017. A decrease in PHI (-35.1%) and PRHI (-25.4%) was observed starting in 2013. The breakpoints for PHI and PRHI were 2012.6 (95% confidence interval [CI], 2010.8-2014.4) and 2013.1 (95% CI, 2011.3-2014.8), respectively., Conclusions: Our findings show that the achievements of 2 public health targets in France and the early initiation of cART were accompanied by a reduction of about one-third in PHI and PRHI between 2013 and 2017., Clinical Trials Registration: NCT02898987., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Safety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy., Objectives: To describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC., Methods: In the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010-18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC., Results: Among 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred., Conclusions: In virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Design: Current international guidelines recommend either boosted protease inhibitor (PI/r)-based or integrase inhibitors (INSTI)-based regimens during primary HIV infection (PHI), even though the latter have only demonstrated their superiority at the chronic stage. We compared the effectiveness of INSTI-based versus PI/r-based combined antiretroviral therapy (cART) initiated during PHI., Methods: This study was conducted among patients who initiated cART between 2013 and 2017, using data from the ANRS-PRIMO cohort and the Dat'AIDS study. Cumulative proportions of patients reaching viral suppression (HIV-1 RNA <50 copies/ml) were calculated using Turnbull's estimator for interval-censored data. CD4 cells and CD4/CD8 ratio increases were estimated using mixed linear models. Results were adjusted for the data source., Results: Among the 712 study patients, 299 received an INSTI-based cART. Patients' baseline characteristics were similar between groups. Viral suppression was reached more rapidly in INSTI-treated versus PI/r-treated patients (P < 0.01), with cumulative proportions of 32 versus 6% at 4 weeks, 72 versus 31% at 12 weeks, 91 versus 78% at 24 weeks and about 95% in both groups at 48 weeks. At 4 weeks, INSTI-treated patients had gained on average 40 CD4 cells/μl (P = 0.05) over PI/r-treated ones; mean CD4 counts were similar in the two groups at 48 weeks. The CD4/CD8 ratio followed the same pattern. Results were similar when restricted to a comparison between dolutegravir-based versus darunavir-based cART., Conclusion: On the basis of this study and available literature, we recommend the use of INSTI-based cART for treatment initiation during PHI, as it leads to faster viral suppression and immune restoration.

We evaluated an elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide single-tablet regimen for human immunodeficiency virus postexposure prophylaxis. The completion rate and adherence were good, and the tolerance was acceptable; no seroconversion was observed. We confirm that this regimen could be appropriate for postexposure prophylaxis., Clinical Trials Registration: NCT02998320., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study has reported an increased risk of cardiovascular diseases in people with human immunodeficiency virus who were exposed to darunavir (DRV) but not to atazanavir (ATV). Our objective was to evaluate associations between ATV or DRV exposures and the risk of myocardial infarction (MI) in a nested case-control study within ANRS-CO4 French Hospital Database on HIV (FHDH)., Methods: Cases were individuals who had a first validated MI between 2006 and 2012. Up to 5 controls were selected at random with replacement among individuals with no history of MI, followed at the time of MI diagnosis, and matched for age and sex. Conditional logistic regression models were used to adjust for potential confounders (MI risk factors and HIV-related parameters) and for cumulative exposure to each antiretroviral drug (ARV)., Results: Overall, 408 MI cases and 1250 controls were included: 109 (27%) cases and 288 (23%) controls had been exposed to ATV, and 41 (10%) cases and 107 (9%) controls had been exposed to DRV. There was no significant association between exposure to ATV (adjusted odds ratio [OR] = 1.54; 95% confidence interval [CI], .87-2.73) or DRV (adjusted OR = 0.51; 95% CI, .11-2.32) and the risk of MI., Conclusions: In FHDH, exposures to ATV or to DRV were not significantly associated with the risk of MI, adjusting for complete ARV history, contrary to the analysis in DAD., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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 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 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 2 per year (p < 0.001). The slope of eGFR reduction was not significantly different in participants with baseline eGFR ≤ 90 mL/min/1.73 m 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 2 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 m 2 , >10 to ≤40ng/mL: -1.28 mL/min/1.73 m 2 , >40 ng/mL: -1.82 mL/min/1.73 m 2 , p < 0.001). Three participants discontinued TDF/FTC for eGFR < 60 mL/min/1.73 m 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., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: A high incidence of acute hepatitis C virus (HCV) (AHCV) infection has been reported among at-risk HIV-negative MSM. The optimal strategy for early diagnosis of AHCV in this population is not clearly defined., Methods: In the ANRS IPERGAY PrEP trial, among high-risk HIV-negative MSM, HCV serology and serum alanine aminotransferase (ALT) were used for screening at enrollment and during follow-up. Behavioral risk factors were compared at baseline between participants who were diagnosed with AHCV during the study compared with those who did not. In participants with a positive HCV serology, we used stored sera to perform the following tests at diagnosis and on previous visits: HCV-antibodies rapid tests, plasma HCV viral load and HCV antigen immunoassay. We evaluated the sensitivity of each test for AHCV diagnosis., Results: Among 429 enrolled participants, 14 were diagnosed with AHCV infection, with a median follow-up of 2.1 (interquartile range, 1.5-2.8) years. AHCV incidence was 1.40 per 100 person-years (95% confidence interval, 0.74-2.39). Patients with AHCV reported a significantly higher number of sexual acts and/or partners, and more frequent recreational drug use at baseline. At the prior visit before AHCV diagnosis (median of 2 months earlier), sensitivities of HCV RNA and HCV antigen tests were, respectively, 100 and 89%, whereas none of the patients had a positive serology, and only 25% had elevated ALT., Conclusion: HCV antigen and RNA tests were positive within a median of 2 months before the detection of antibodies and ALT elevation. These tests could be considered for HCV screening in high-risk MSM.

Background: Sexually transmitted acute hepatitis C virus (HCV) infections (AHIs) have been mainly described in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Cases in HIV-negative MSM are scarce. We describe the epidemic of AHI in HIV-infected and HIV-negative MSM in Lyon, France., Methods: All cases of AHI diagnosed in MSM in Lyon University Hospital from 2014 to 2017 were included. AHI incidence was determined in HIV-infected and in preexposure prophylaxis (PrEP)-using MSM. Transmission clusters were identified by construction of phylogenetic trees based on HCV NS5B (genotype 1a/4d) or NS5A (genotype 3a) Sanger sequencing., Results: From 2014 to 2017, 108 AHIs (80 first infections, 28 reinfections) were reported in 96 MSM (HIV-infected, 72; HIV-negative, 24). AHI incidence rose from 1.1/100 person-years (95 confidence interval [CI], 0.7-1.7) in 2014 to 2.4/100 person-years (95 CI, 1.1-2.6) in 2017 in HIV-infected MSM (P = .05) and from 0.3/100 person-years (95 CI, 0.06-1.0) in 2016 to 3.4/100 person-years (95 CI, 2.0-5.5) in 2017 in PrEP users (P < .001). Eleven clusters were identified. All clusters included HIV-infected MSM; 6 also included HIV-negative MSM. All clusters started with ≥1 HIV-infected MSM. Risk factor distribution varied among clusters., Conclusions: AHI incidence increased in both HIV-infected and HIV-negative MSM. Cluster analysis suggests initial transmission from HIV-infected to HIV-negative MSM through chemsex and traumatic sexual practices, leading to mixed patterns of transmission regardless of HIV status and no overlap with the general population., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France., Methods: Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients' baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription., Results: From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 years = 1.76, 95% CI 1.35-2.3, P < 0.001) and site of prescription (OR of former IPERGAY sites = 2.28, 95% CI 1.84-2.83, P < 0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (OR = 0.68, 95% CI 0.57-0.82 and 0.75, 95% CI 0.57-0.98, respectively; P < 0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation., Conclusions: In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

ANRS-IPERGAY was a community-based randomized trial investigating the efficacy of sexual activity-based HIV pre-exposure prophylaxis (PrEP) in a population of males and transgender females who had sex with men and were at high risk of HIV infection. We qualitatively analyzed the support provided to participants by community-based health workers (CBHW) throughout the trial's double-blind and open-label extension phases. In particular, we showed that the relationship between participants and CBHW strongly influenced self-managed pill intake. The delicate construction of this relationship, balanced between trust and dependence, played an important role in PrEP adherence. CBHW had to deal with various issues surrounding participants' feelings of empowerment regarding their role in the trial, as well as related tensions between various logics and rationalities. They were essential to participants' continued involvement.

Objective: To describe the changes in first-line antiretroviral (ART) regimens in France between 2005 and 2015 and patients' characteristics related to the use of protease inhibitors in 2015., Methods: We extracted all patients starting ART between 2005 and 2015 from a large prospective cohort. Regimens were classified as three nucleoside reverse transcriptase inhibitors (NRTI), or two NRTIs with a boosted protease inhibitor (bPI), with a non-nucleoside reverse transcriptase inhibitor (NNRTI), or with an INSTI. Patients' characteristics at the time of initiation were collected. A multinomial logit model was fitted to analyze characteristics related to the choice of regimen in 2015., Results: We analyzed data from 15,897 patients. The proportion of patients starting with (i) a bPI decreased from 60% before 2014 to 38.1% in 2015; (ii) an NNRTI decreased from 30% to 17.8% in 2015; (iii) an INSTI gradually increased to 39.4% in 2015. In 2015, patients with an initial viral load ˃5 log copies/mL were less likely to receive NNRTI (OR=0.08) or INSTI regimens (OR=0.69) than bPIs. Patients with initial CD4 + T cell count ˂200/mm 3 were less likely to receive an NNRTI (OR=0.28) or an INSTI regimen (OR=0.52) than a bPI. Women were less likely to receive an NNRTI (OR=0.79) or an INSTI regimen (OR=0.71) than a bPI; although this depended on age., Conclusion: The use of bPI as first-line ART declined sharply in France from 2005 to 2015. bPI remained of preferential use in patients with high viral load, low CD4 + T cell count, and in women., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Sexual life is an important dimension of quality of life, which may be affected by the fear of transmission in people living with HIV/AIDS (PLWHA), despite the fact that antiretroviral therapy prevents person-to-person transmission. We, therefore, aimed to explore the sexual life satisfaction of PLWHA and its correlation with their fear of HIV transmission and self-esteem. Consecutive adult PLWHA from seven HIV care facilities in the Rhone-Alpes region, France, were asked to complete a self-administered, anonymous questionnaire concerning sociological and medical data, satisfaction with sexual life (18 questions), and self-esteem (Rosenberg score). Overall, 690 PLWHA answered the questionnaire (mean age 49.2 ± 11 years); 74.9% were men, of which 75.1% had sex with men. Overall, 68.0% of respondents feared transmitting HIV (a lot/a bit). A lower satisfaction with sexual life was significantly associated with being female, not having a stable sexual partner, being unemployed, having a low income, experiencing a fear of HIV transmission, having lower self-esteem, and not reporting an excellent/very good health status. These results strongly suggest that the information concerning the antiretroviral-induced suppression of infectivity should be widely diffused, as this may enhance the quality of sexual life in PLWHA.

Introduction: Achieving functional cure of chronic HBV infection (Hepatitis B surface antigen [HBsAg] clearance, eventually followed by acquisition of anti-hepatitis B surface antigen [Anti-HBs]) in individuals with HIV and HBV infections is a rare event. In this setting, factors related to HBV cure have not yet been fully characterized., Methods: HIV-infected individuals with chronic HBV infection enrolled in the French Dat'AIDS cohort (NCT02898987), who started combined antiretroviral (cART)-anti-HBV treatment were retrospectively analyzed for HBsAg loss and Anti-HBs seroconversion., Results: Overall, 1419 naïve-subjects received three different cART-anti-HBV treatment schedule: (1) 3TC or FTC only (n = 150), (2) TDF with or without 3TC or FTC (n = 489) and (3) 3TC or FTC as first line followed by adding/switching to TDF as second line (n = 780). Individuals were followed-up for a median of 89 months (IQR, 56-118). HBV-DNA was < 15 IU/mL in 91% of individuals at the end of the follow-up. Overall, 97 individuals cleared HBsAg (0.7/100 patient-years), of whom, 67 seroconverted for Anti-HBs (0.5/100 patient-years). A high CD4 nadir, a short delay between HBV diagnosis and treatment, a longer time on HBV therapy, an African origin and TDF-based therapy were independent predictors of HBsAg clearance (Probability of odds ratio [OR]>1, >95%) suggested by Bayesian analysis. Also, TDF-based regimen as first line (OR, 3.03) or second line (OR, 2.95) increased rates of HBsAg clearance compared to 3TC or FTC alone, with a 99% probability., Conclusions: HBsAg clearance rate was low in HIV-HBV co-infected cART-anti-HBV treated individuals, but was slightly improved on TDF-based regimen., Competing Interests: The authors have declared that no competing interests exist.

Background: HIV pre-exposure prophylaxis (PrEP) was implemented in France in November 2015 based on individual-level risk factors for HIV infection. We evaluated the proportion of missed opportunities for PrEP among newly HIV-diagnosed people entering the Dat'AIDS cohort in 2016., Methods: Multicenter retrospective analysis in 15 French HIV clinical centers of patients with a new diagnosis of HIV infection. Among them we differentiated patients according to the estimated date of infection: those occurring in the PrEP area (a previous negative HIV test in the last 12 months or those with an incomplete HIV-1 western blot (WB) with no HIV-1 anti-Pol-antibody at time of HIV diagnosis) and those in the pre-PrEP area (older infections). Epidemiological, biological and clinical data at HIV diagnosis were collected. Clinicians retrospectively identified potential eligibility for PrEP based on individual-level risk factors for HIV infection among those infected in the PrEP area., Results: Among 966 patients with a new HIV diagnosis, 225 (23.3%) were infected in the PrEP area and 121 (53.8%) had complete data allowing evaluation of PrEP eligibility. Among them, 110 (91%) would have been eligible for PrEP, median age 31 years, with 68 (75.6%) born in France and 10 (11.1%) in Central/West Africa, with more than one previous STI in 19 (15.7%). The main eligibility criteria for PrEP were being a man who had sex with men or transgender 91 (82.7%) with at least one of the following criteria: unprotected anal sex with ≥2 partners in the last 6 months: 67 (60.9%); bacterial sexually transmitted infection in the last 12 months: 33 (30%); Use of psychoactive substances in a sexual context (chemsex): 16 (14.5%). PrEP was indicated for other HIV risk factors in 25 (22.7%)., Conclusion: With 91% (110/121) of patients infected in the PrEP area eligible for PrEP, this study highlights the high potential of PrEP in avoiding new infection in France but also shows a persistent delay in HIV testing. Thus, an important limit on PrEP implementation in France could be insufficient screening and care access.

We examined trends in the MI incidence and age at MI diagnosis among adults living with HIV-1 between 2000 and 2009, by comparison with the French MI registries, by gender. Age standardized incidence rates and standardized incidence-ratios (SIRs) were estimated for individuals included in the French hospital database on HIV (n = 71 204, MI = 663) during three periods: 2000-2002, 2003-2005 and 2006-2009. Median ages at MI diagnosis were compared using the Brown-Mood test. Over the study periods, the absolute rate difference and relative risks were higher in women than in men in 2000-2002 and 2006-2009, with respective SIRs 1.99 (1.39-2.75) and 1.12 (0.99-1.27) in 2006-2009. The trends were different for men and women with a decreasing trend in SIRs in men and no change in women. In both sexes, among individuals with CD4 ≥500/μL and controlled viral-load on cART, the risk was no longer elevated. Age at MI diagnosis was significantly younger than in the general population, especially among women (-6.2 years, p<0.001; men: -2.1 years, p = 0.02). In HIV-1-positive adults, absolute rate difference and relative risks and trends of MI were different between men and women and there was no additional risk among individuals on effective cART., Competing Interests: Aliou BALDE was supported by the Fogarty International Center of the National Institutes of Health under Award Number D43TW007995 and D43TW010350. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All authors declare no conflict of interest, although several members of the group have, at some stage in the past, received funding from a variety of pharmaceutical companies for research, travel grants, speaking engagements or consultancy fees. Sylvie Lang has received travel grants from Boehringer-Ingelheim. Laurent Cotte has received study grants from ViiV Healthcare and MSD; personal fees from BMS, Gilead Sciences, Janssen, MSD and ViiV healthcare. Jean Ferrières has received grants and lecture fees from Amgen, Merck, and Sanofi. Elisabeth Aslangul has received travel grants from Sanofi, Pfizer and Bristol-Myers-Squibb. Antoine Chéret has received study grants from Merck and personal fees from Gilead, ViiV Healthcare, and Janssen. Jean-Luc Meynard has received honoraria from Gilead, Abbott, ViiV Healthcare and BMS. Jean-Michel Molina has received study grants from Merck and Gilead Sciences; advisory board member for Merck, Gilead Sciences, Janssen, ViiV Healthcare, BMS, and Teva, and a speakers’ bureau for Gilead. Franck Boccara has received study grant from Amgen, speaker fees from AstraZeneca, Merck; advisory board member for Amgen, Sanofi, Gilead, and ViiV Healthcare. Dominique Costagliola has received travel grants, consultancy fees, honoraria or study grants from Abbott, Boehringer-Ingelheim, Bristol-Myers-Squibb, Gilead Sciences, Glaxo-Smith-Kline, Janssen, Merck and Roche.There are no patents, products in development, or marketed products to declare. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.

Background: The IPERGAY ANRS trial showed that on-demand preexposure prophylaxis (PrEP) with tenofovir (TDF) and emtricitabine (FTC) was highly effective in preventing HIV infection among highly exposed MSM. Here, we analyzed drug resistance-associated mutations (RAMs) among all participants who acquired HIV infection during this trial., Methods: Resistance was analyzed on frozen plasma at the time of HIV diagnosis among participants enrolled in the double-blind and open-label phases of the ANRS IPERGAY trial. Reverse transcriptase sequencing was performed, using population-based and ultradeep sequencing (454 GS Flex). Adherence was measured by pill counting and by plasma tenofovir and FTC assay., Results: During the trial, 31 participants were diagnosed with HIV-1 infection (subtype B, 64.5%), using antigen/antibody immune assay in 29 cases and plasma HIV RNA assay in two. The median plasma HIV-1 RNA level was 5.52 log10 copies/ml. Drug resistance was tested in 12 participants before starting PrEP, in six assigned to TDF/FTC group and in 13 assigned to placebo group. Primary resistance to nucleoside reverse transcriptase inhibitors (zidovudine) and/or nonnucleoside reverse transcriptase inhibitors was detected in six participants (19%; 95% confidence interval 7-42). No major or minor TDF-resistant or FTC-resistant variants were detected., Conclusion: No TDF or FTC resistance-associated mutations were found among participants who acquired HIV in the ANRS IPERGAY trial.

Background: Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections have been reportedly associated with a higher risk of diabetes mellitus (DM) but results are conflicting., Aims: To determine whether there is an association between chronic HCV and the incidence of DM, and to study the role of factors such as cirrhosis, IFN-based HCV therapy, sustained virologic response (SVR) and chronic HBV infection among patients living with HIV (PLHIV) followed in a large French multicentre cohort in the combination antiretroviral therapy (cART) era., Methods: All PLHIV followed up in the Dat'AIDS cohort were eligible. Cox models for survival analysis were used to study the time to occurrence of DM., Results: Among 28 699 PLHIV, 4004 patients had chronic HCV infection. The mean duration of HCV follow-up was 12.5 ± 8.1 years. The rate ratio of DM was 2.74 per 1000 person-years. By multivariate analysis, increasing age, body mass index>25, AIDS status, nadir CD4 cell count ≤200/mm 3 , detectable HIV viral load and cirrhosis (HR 2.26 95% CI 1.14-1.18; P < 0.0001) were predictors of DM, whereas longer cART duration was associated with a lower risk of DM. Chronic HCV and HBV infection and IFN-based HCV therapy were not associated with DM. In a subanalysis among HCV-infected patients, SVR was not related to DM., Conclusions: Our study shows that in the HIV population, cirrhosis is associated with an increased occurrence of DM, but not chronic HCV infection or duration of HCV infection., (© 2018 John Wiley & Sons Ltd.)

The ANRS-IPERGAY trial consisted in providing sexual activity-based antiretroviral prophylaxis for HIV prevention (PrEP) with a package of prevention tools (counselling, condoms, HIV and sexually transmitted infections' screening) to highly exposed HIV-negative men who have sex with men (MSM). Few data exist concerning the patient-physician relationship in the particular context of PrEP, where physicians discuss sexual behaviours with MSM who are not classic patients, in that consultation is for prevention purposes, not for illness. This study took place during the open-label extension of ANRS-IPERGAY trial when all participants received PrEP. In this qualitative study, we examined how physicians perceived their relationship with participants in the ANRS-IPERGAY trial. Of all 30 physicians involved in the trial who were contacted by email to participate in an interview about their opinions and perceptions of ANRS-IPERGAY 18 volunteered to participate in the current sub-study. We performed a vertical analysis for each interview to identify the extract in each physician's discourse concerning their relationship with MSM participants, and conducted a horizontal analysis to construct the thematic tree and subsequently investigate differences and similitudes between themes. An analysis of all physicians' discourses showed that the participant-physician relationship during the trial could be described through 4 themes: (i) personal experience of the relationship, (ii) trust and non-judgement, (iii) positive relational climate and (iv) influence of physician's characteristics (age, gender, etc.) on relationship. We found that the particular context of PrEP led some physicians to adopt a patient-as-partner approach during consultations rather than a paternalist or hierarchical approach. Indeed, the close follow-up provided by the trial and the active role of patients in their own prevention care trajectory, are more compatible with the patient-as-partner approach. The prescription of PrEP may lead to an evolution in patient-physician relationships and may even modify the professional identity of physicians.

Objective: High hepatitis C virus (HCV) treatment uptake combined with effective direct-acting antiviral-based regimens resulted in a dramatic decline of HCV infection in French people living with HIV (PLWH). We assessed the yearly incidence of new HCV infection in PLWH enrolled in the large French Dat'AIDS cohort from 2012 to 2016 with a specific focus on MSM., Methods: The incidence of new HCV infection was determined yearly in HCV-negative PLWH with serological follow-up during 2012-2016. The incidence of HCV reinfection was determined in patients who were cured of a previous infection., Results: Among 40 714 PLWH, HCV status was available in 38 217 (94%). A total of 5557 PLWH (15%) were HCV infected at first time-point, 82% of whom were cured of HCV by the end of 2016. Among 21 519 HCV-negative PLWH with serological follow-up (63 449 patient-years), 219 first HCV infections occurred (MSM: 188, others: 31). Similarly, among 3406 patients who were cured of a previous infection (10 602 patient-years), 73 reinfections occurred (MSM: 51, others: 22). From 2012 to 2016, the incidence of a first infection in MSM rose from 0.5 to 0.92% patient-years, whereas the incidence or reinfection remained stable (2.52-2.90% patient-years)., Conclusion: Despite a high HCV treatment uptake and cure rate, the incidence of first HCV infection regularly increased in French HIV-positive MSM between 2012 and 2016. The incidence of reinfection fluctuated but remained constantly higher than the incidence of first infection, suggesting that a subgroup of MSM pursued high-risk practices following cure of a first infection.

Objectives: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis., Methods: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes., Results: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified., Conclusions: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis., (© 2017 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objectives: The aim of the study was to determine whether there is a relationship between social deprivation and time of HIV diagnosis in France., Methods: Prospectively collected data from a multicentre database were used in the study. Patients with a first HIV diagnosis between 1 January 2014 and 31 December 2015 were selected from the database. Deprivation was measured using the European Deprivation Index (EDI), which is an ecological index constructed from the address of residence and based on the smallest geographical census unit, in which individuals are classified so as to be comparable with national quintiles. Time of diagnosis was classified as being at an early, intermediate, late, or advanced stage of disease. Age, gender, distance from home to HIV centre, most probable route of infection, and hepatitis B or C coinfection were considered in the analysis. Because of a strong interaction between gender and most probable route of infection, we constructed a 'population' variable: men who have sex with men (MSM), heterosexual men and women., Results: Of 1421 newly diagnosed patients, 44% were diagnosed either late or at an advanced stage of disease, and 46.3% were in the highest deprivation quintile. Using multivariate logistic regression, 'population' [odds ratio (OR) 0.62 (95% confidence interval (CI) 0.48-0.78) for MSM compared with women] and age [OR 1.39 (95% CI 1.07-1.80), 1.72 (1.32-2.23) and 1.86 (1.40-2.47) for the second, third and fourth quartiles, respectively, compared with the first quartile] were found to be related to late diagnosis. EDI level was not related to late HIV diagnosis., Conclusions: 'Population' seems to be more relevant than EDI to define evidence-based interventions to limit late diagnosis., (© 2017 British HIV Association.)

Objectives: We undertook the economic evaluation of the double-blind randomized ANRS-IPERGAY trial, which showed the efficacy of on-demand preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) in preventing HIV infection among high-risk MSM., Design and Methods: The economic evaluation was prospective. Counseling, drugs (TDF-FTC at &OV0556;500.88 for 30 tablets), tests, visits, and hospital admissions were valued based on in-trial use. The cost of on-demand PrEP/HIV infection averted was compared with the yearly and lifetime costs of HIV infection in France in a cost and benefits analysis., Results: The yearly number of participants needed to treat to prevent one HIV infection was 17.6 (95% confidence interval = 10.7-49.9). The annual cost of counseling was &OV0556;690/participant. The total 1-year costs of PrEP were &OV0556;4271/participant, of which &OV0556;3129 (73%) were drug costs corresponding to 15 tablets of TDF-FTC/month. The yearly cost of on-demand PrEP to avoid one infection was &OV0556;75 258. Using TDF-FTC generic (&OV0556;179.9/30 tablets) reduced the 1-year costs of on-demand PrEP to &OV0556;2271/participant and &OV0556;39 970/infection averted, respectively. Using TDF-FTC at international market discounted prices (&OV0556;60/30 tablets) reduced the costs to &OV0556;1517/participant and the cost to &OV0556;26 787/infection averted, comparable with the yearly treatment cost of HIV infection in France. On-demand PrEP was found to be cost saving in France if the duration of exposure was less than 7.5 years at current drug price and 13 years at generic price., Conclusion: On-demand PrEP in high-risk MSM with TDF-FTC can be considered cost saving. Other benefits include the treatments of other diseases and reductions in secondary infections.

Background: HCV treatment uptake has drastically increased in HIV-HCV coinfected patients in France since direct-acting antiviral (DAA) treatment approval, resulting in HCV cure in 63% of all HIV-HCV patients by the end of 2015. We investigated the impact of scaling-up DAA on HCV prevalence in the whole HIV population and in various risk groups over the next 10 years in France using a transmission dynamic compartmental model., Methods: The model was based on epidemiological data from the French Dat'AIDS cohort. Eight risk groups were considered, including high-risk (HR) and low-risk (LR) men who have sex with men (MSM) and male/female heterosexuals, intra-venous drug users, or patients from other risk groups. The model was calibrated on prevalence and incidence data observed in the cohort between 2012 and 2015., Results: On January 1, 2016, 156,811 patients were registered as infected with HIV in France (24,900 undiagnosed patients) of whom 7938 (5.1%) had detectable HCV-RNA (722 undiagnosed patients). Assuming a treatment coverage (TC) rate of 30%/year (i.e., the observed rate in 2015), model projections showed that HCV prevalence among HIV patients is expected to drop to 0.81% in 2026. Sub-analyses showed a similar decrease of HIV-HCV prevalence in most risk groups, including LR MSM. Due to higher infection and reinfection rates, predicted prevalence in HR MSM remained stable from 6.96% in 2016 to 6.34% in 2026. Increasing annual TC rate in HR MSM to 50/70% would decrease HCV prevalence in this group to 2.35/1.25% in 2026. With a 30% TC rate, undiagnosed patients would account for 34% of HCV infections in 2026., Conclusions: Our model suggests that DAA could nearly eliminate coinfection in France within 10 years for most risk groups, including LR MSM. Elimination in HR MSM will require increased TC.

Objective: We investigated whether patients receiving selected antiretroviral combinations had a higher risk of chronic kidney disease (CKD) using traditional regression modeling and a causal approach in a large prospective cohort., Patients and Methods: For the purpose of this study, we selected 6301 patients who (i) started their first antiretroviral regimen after 1st January 2004, (ii) had at least one serum creatinine measurement within 6 months before ART initiation (study entry), and (iii) had at least two measurements after study entry. Baseline eGFR was defined from the last serum creatinine measurement before study entry. All eGFR values were calculated using the Modification of Diet and Renal Disease (MDRD) equation. Both traditional Cox proportional hazards model and Cox marginal structural models were applied. Distinct coding for antiretroviral therapy exposure were investigated as well as double robust estimators., Results: Overall we showed that patients receiving tenofovir (TDF) with a ritonavir boosted protease inhibitor (rbPI) exhibited a higher risk of CKD compared with patients who received TDF with a non-nucleosidic reverse transcriptase inhibitor (NNRTI). Such an increased risk was observed considering both initial and current regimens. Our analysis revealed a clinician-driven switch away from TDF among persons experiencing a decline in renal function while receiving this drug., Conclusion: Our results show that combination of TDF and boosted protease inhibitor is associated with a higher CKD risk than TDF and a NNRTI.

Since 2016, an increase in the number of hepatitis A cases affecting mainly men who have sex with men (MSM) has been reported in low endemic countries in Europe. We calculated the attack rate in Lyon, France, in populations considered at high-risk: HIV-infected MSM and HIV-negative MSM receiving HIV pre-exposure prophylaxis (PrEP). In these populations, high level of immunity did not prevent the outbreak, indicating that vaccination should be reinforced, particularly in younger individuals.

Background: HIV infection and inflammatory and autoimmune diseases (IADs) are both related to immune dysfunction. Epidemiological data on IAD in patients living with HIV (PLHIV) are scarce. The aim of this study was thus to estimate the prevalence of 26 IAD among PLHIV followed in a large French multicenter cohort in the combination antiretroviral therapy (cART) era (from January 2000 to July 2013), and to describe their occurrence according to cART onset, the immuno-virological status of patients and hepatitis C virus (HCV) and/or hepatitis B virus coinfection., Method and Results: During the study period, 33 403 PLHIV were included in the Dat'AIDS cohort; 1381 patients with an IAD were identified. The most prevalent IADs were psoriasis, sarcoidosis, rheumatoid arthritis, ankylosing spondyloarthritis, Grave's disease, autoimmune hemolytic anemia, immune thrombocytopenia and chronic inflammatory bowel disease. In contrast, the prevalence of systemic lupus erythematosus and multiple sclerosis were low. Most patients (59%) developed IAD after HIV infection with a mean delay of 10.6 ± 6.4 years. Compared with the entire cohort, HCV coinfection was significantly more frequent in patients with psoriasis, Grave's disease and immune thrombocytopenia, and chronic hepatitis B in patients was more frequent in those with immune thrombocytopenia and autoimmune hemolytic anemia. Among patients developing IAD after the diagnosis of HIV infection, 572 (70%) were on antiretroviral therapy and 419 of them (73%) had undetectable HIV viral load., Conclusion: Our study showed that some IAD are not rare among PLHIV and occur mostly in patients with immuno-virological control under cART. The higher frequency of HCV or hepatitis B virus coinfection for some IAD is also confirmed.

Objectives: Direct-Acting Antivirals (DAAs) opened a new era in HCV treatment. We report the impact of HCV treatment in French HIV-HCV coinfected patients., Methods: All HIV-HCV patients from the Dat'AIDS cohort followed between 2012 and 2015 were included. HCV status was defined yearly as naive, spontaneous cure, sustained virological response (SVR12), failure or reinfection., Results: Among 32,945 HIV-infected patients, 15.2% were positive for anti-HCV antibodies. From 2012 to 2015, HCV incidence rate increased from 0.35%PY to 0.69%PY in MSM, while median incidence was 0.08%PY in other patients. Median reinfection rate was 2.56%PY in MSM and 0.22%PY in other patients. HCV treatment initiation rate rose from 8.2% in 2012 to 29.6% (48.0% in pre-treated patients vs 22.6% in naïve patients). SVR12 rate increased from 68.7% to 95.2%. By the end of 2015, 62.7% of the patients were cured either spontaneously or following SVR., Conclusions: HCV treatment dramatically increased in HIV-HCV patients in France from 2012 to 2015 resulting in HCV cure in nearly two-thirds of the patients in this cohort. Combined with a declining HCV prevalence, the prevalence of active HCV infection among HIV patients will drastically decrease in the forthcoming years., (Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: The aim of the study was to describe the ageing HIV-infected population (> 50 years old) and their current antiretroviral therapy (ART), comorbidities and coprescriptions in France in 2013 and to compare them to the younger population., Methods: A retrospective analysis of a prospectively collected database was performed. The characteristics of patients receiving ART as well as their current ART and their numbers of comorbidities and comedications at the censoring date (1 July 2013) were compared between patients ageing with HIV infection, patients who seroconverted while ageing, and younger patients., Results: We compared 10 318 ageing patients [median age 56 years; 25% interquartile range (IQR) 53-62 years] with 13 302 younger patients (median age 42 years; 25% IQR 36-47 years). The ageing patients were more frequently male than the younger patients (77 vs. 65%). Among the ageing patients, 7025 were diagnosed with HIV infection before 2000 and represented a distinct group, the 'experienced ageing' group, by comparison with the 'recently diagnosed ageing' group. Triple therapy containing a boosted protease inhibitor was used in 28.2% of the patients (vs. 39% and 36% of the younger and "recently diagnosed ageing" groups, respectively); a nonnucleoside reverse transcriptase inhibitor in 27% (vs. 33% and 38%, respectively), an integrase strand transfer inhibitor (INSTI) in 9% (vs. 7% and 9%, respectively), and another regimen (fewer or more than three drugs) in 35.8% (vs. 21% and 16.5%, respectively). "Experienced ageing" patients typically had one or more comorbidities (62.1%) and were receiving at least one comedication (71%). Central nervous system (CNS) agents (prescribed in 44.6% of the "experienced ageing" patients) and antilipidaemics (in 44.2%) were the most frequently prescribed comedications. INSTIs were used in 23% of the population and were used significantly more often in patients with comorbidities and coprescriptions. For all comparisons, P < 0.0001., Conclusions: In ageing HIV-infected patients, especially those with a long history of HIV infection, comorbidities and coprescriptions are highly prevalent., (© 2016 British HIV Association.)

Objective: Poorer immunologic responses to combined antiretroviral treatment (cART) have been reported among sub-Saharan African (SSA) migrants than among native Europeans. We studied whether differences in CD4 cell recovery between French natives and SSA migrants starting first-line cART could be explained by differences in socioeconomic conditions, inflammatory marker levels, and other established determinants., Methods: We compared 319 French natives and 175 SSA migrants (ANRS-COPANA cohort). Clinical, biological, and socioeconomic data (education, employment, income, and cohabiting partnership) were recorded at regular visits. A piecewise linear mixed-effects model was used to analyze CD4 cell count kinetics on cART., Results: Compared with French natives, SSA migrants were more frequently women, younger, less educated, living in more adverse conditions, and had more frequent symptoms of depression. The rate of CD4 cell recovery during the first 4 months on cART was significantly slower in SSA migrants, despite a similar virologic response, but did not differ significantly thereafter. The mean CD4 cell count rose from 251 cells/μl at baseline to 508 cells/μl at 36 months in migrants, and from 308 to 623 cells/μl in natives (additional mean gain of 58 cells/μl in natives). The difference persisted after adjustment for clinical, updated socioeconomic, and living conditions (-0.40√CD4 cells/month, P = 0.04); 25-hydroxyvitamin D, monocyte chemoattractant protein-1 and soluble tumor necrosis factor receptor 1 (sTNFR1) levels were lower in SSA migrants, but only sTNFR1 contributed to the difference in CD4 slope., Conclusion: Initial CD4 cell recovery on cART was slower among SSA migrants than among French natives. This difference was not explained by established clinical and biological determinants or by socioeconomic status.

Objectives: Pill burden during antiretroviral treatment (ART) is associated with worse adherence and impaired virological suppression. We compared the effectiveness, tolerance, and persistence on treatment of single tablet regimens (STRs) with non-STR once-daily regimens in patients receiving first-line ART., Methods: Retrospective analysis of naïve HIV-1 infected patients prospectively enrolled in the French Dat'AIDS cohort and initiating first-line ART with STRs or once-daily non-STRs from 2004 to 2013. The primary outcome was time to treatment discontinuation defined by any change in the treatment regimen. STR and non-STR groups were compared controlling for baseline risk factors by inverse probability weighted treatment Cox analysis (IPWT) and propensity-score matching (PSM)., Results: Overall, 3212 patients (STR 499, non-STR 2713) were included. Median time to treatment discontinuation was shorter in non-STR patients than in STR patients, both in the IPWT (HR = 0.61, p<0.0001) and the PSM cohort (HR = 0.55, p<0.0001). This difference disappeared when censoring ART modification for simplification, both in the IPWT (HR = 0.97, p = 0.65) and the PSM cohort (HR = 0.91, p = 0.33). A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and HR = 0.22, p = 0.003, respectively). A lower rate of treatment modification for adverse event was observed with non-STRs in the IPWT cohort (HR = 1.46, p<0.0001), but not in the PSM cohort (HR = 1.22, p = 0.11)., Conclusion: First-line therapy with STRs was associated with a longer time to treatment discontinuation than with non-STRs. However, when ART modification for simplification was not considered as a failure, STRs and non-STRs were similar., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr Cotte reports grants from ViiV Healthcare, MSD, non-financial support from Gilead, Janssen, BMS, ViiV Healthcare, MSD, Abbott, outside the submitted work and personal fees from Gilead, Janssen, BMS, ViiV Healthcare, MSD, Abbott. Dr Ferry has nothing to disclose. Dr Pugliese has nothing to disclose. Dr Valantin reports personal fees from ViiV Healthcare, personal fees from Janssen, other conflict of interest from BMS and MSD, outside the submitted work. Dr Allavena reports personal fees from Gilead, BMS, ViiV Healthcare, MSD and Janssen, outside the submitted work. Dr Cabié reports non-financial support from Gilead, Janssen, ViiV Healthcare, MSD, outside the submitted work. Dr Poizot-Martin reports personal fees from Gilead, personal fees from BMS, personal fees from Abbvie, personal fees from ViiV Healthcare, outside the submitted work. Dr Rey reports personal fees from Gilead, non-financial support from Gilead, MSD, and BMS, outside the submitted work. Dr Duvivier reports grants from Gilead, grants from BMS, Janssen, ViiV Healthcare, and MSD, outside the submitted work. Dr Chéret has nothing to disclose. Dr Dellamonica has nothing to disclose. Dr Parienti has nothing to disclose. Pierre Pradat performed medical writing services and received financial support from Dat’AIDS. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Tenofovir disoproxil fumarate is associated with renal and bone toxicity. In a single-arm, open-label study of 242 virologically suppressed, HIV-infected participants with creatinine clearance 30-69 mL/min who switched to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, participants had stable creatinine clearance, significant and durable improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001), and significant increases in hip and spine bone mineral density through 96 weeks (P < 0.001). Eighty-eight percent maintained HIV-1 RNA <50 c/mL at week 96. These longer-term results support the use of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-infected individuals with mild-moderately impaired renal function., Competing Interests: F.A.P. reports receiving research grant to institution from Gilead and ViiV, and personal fees from Gilead, ViiV, Janssen, MSD, and Abbvie. P.T. reports receiving consulting fees from Merck and research grant to institution for Gilead trials and has serve on adjudication committee for GlaxoSmithKline. L.C. has received research grants from MSD, and ViiV; personal fees from Mylan; and nonfinancial support from MSD, ViiV, Janssen, Gilead, and BMS. M.E.A., S.J., A. Cheng, M.D., and M.W.F. are employees of Gilead and hold stock interest in the company. The remaining authors have no conflicts of interest to disclose.

Objective: We assessed the virological efficacy of a 6 month maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy combining tenofovir disoproxil fumarate/emtricitabine with maraviroc/raltegravir., Methods: HIV-1-infected naive patients were enrolled in an open label, single-arm, Phase 2 trial. All patients received maraviroc 300 mg twice daily, raltegravir 400 mg twice daily and tenofovir/emtricitabine for 24 weeks. Patients with stable HIV-RNA <50 copies/mL stopped tenofovir/emtricitabine at week (W) 24 and pursued maraviroc/raltegravir until W48. The primary endpoint was the virological response defined by HIV-RNA <50 copies/mL at W48., Results: Thirty-three patients were analysed. Patients were mostly male (94%), Caucasians (91%), MSM (82%); their median age was 42 years. At baseline, median CD4 cell count was 453 cells/mm 3 and HIV-RNA was 4.3 log copies/mL. All patients had CCR5-tropic viruses by genotropism and phenotropism assays. All but one patient had an HIV-RNA < 50 copies/mL at W24 and entered the simplification phase. Virological success was maintained at W48 in 88% (90% CI 79%-97%) of patients. N155H mutation was detected at failure in one patient. No tropism switch was observed. Raltegravir and maraviroc plasma exposure were satisfactory in 92% and 79% of 41 samples from 21 patients. Five severe adverse events (SAEs) were observed up to W48; none was related to the study drugs. Four patients presented grade 3 AEs; none was related to the study. No grade 4 AE was observed. No patient died., Conclusions: Maraviroc/raltegravir maintenance therapy following a 6 month induction phase with maraviroc/raltegravir/tenofovir/emtricitabine was well tolerated and maintained virological efficacy in these carefully selected patients., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The aim of preventive measures against human immunodeficiency virus (HIV) is to reduce the incidence of HIV infection in the general population and in high-risk groups, such as men having sex with men (MSM), and to reduce the risk that a given individual will contract or spread the virus. Male and female condoms, post-exposure prophylaxis and circumcision are preventive methods currently recognized or promoted worldwide. Although modest success has been reported in a phase-III vaccine trial, other methods are being evaluated, such as vaginal and rectal microbicides, and pre-exposure prophylaxis (PrEP). Herein, we discuss results from prevention trials, especially those focusing on PrEP and particularly on recent results from 'on-demand' PrEP regimens. The efficacy of PrEP (rates of 0%-86%) is strongly correlated with adherence and plasma concentrations of antiretrovirals. Adverse events are rare. Selection of emtricitabine-resistant strains is mainly reported in individuals with an undiagnosed HIV infection using PrEP. PrEP is now strongly recommended in WHO prevention programmes for individuals at substantial risk for HIV with a view to controlling this epidemic by 2030., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Data on the long-term efficacy and safety of abacavir/lamivudine (ABC/3TC) and nevirapine (NVP) are scarce. This combination has the advantage of simplifying treatment and improving long-term tolerance. The aim of this study was to compare the rate of any discontinuation of antiretroviral (ARV) regimen because of virologic failure (VF), and/or adverse drug reaction (ADR) among patients receiving stable ARV regimens for at least 6 months.ABC/3TC/NVP was compared to ABC/3TC with either ritonavir-boosted darunavir (DRV/r) or ritonavir-boosted atazanavir (ATV/r), unboosted ATV, or tenofovir/emtricitabine (TDF/FTC) with either one of the following: ATV/r, unboosted ATV, DRV/r, efavirenz (EFV), or NVP, in the French prospective multicenter Dat'AIDS cohort.The study enrolled 16,511 patients treated with following ARV regimens: ABC/3TC/NVP (n = 1089), TDF/FTC/NVP (n = 1542), ABC/3TC/DRV/r (n = 1065), ABC/3TC/ATV/r (n = 1847), ABC/3TC/ATV (n = 563), TDF/FTC/ATV/r (n = 3519), TDF/FTC/DRV/r (n = 2767), TDF/FTC/ATV (n = 419), and TDF/FTC/EFV (n = 3700). Mean follow-up was 36 ± 24 months. Patients treated with ABC/3TC/NVP received this regimen as a switch regimen in 97% of cases. By multivariable analysis, the risk of treatment discontinuation due to VF was similar between ABC/3TC/NVP and other ARV regimens, except for TDF/FTC/ATV and ABC/3TC/ATV, which were associated with a higher risk of treatment interruption due to VF (hazard ratio [HR] 1.99; 95% confidence interval [CI] 1.29-3.06 and HR 2.19; 95% CI 1.51-3.18, respectively). Treatment discontinuation due to ADR was lowest with the ABC/3TC/NVP regimen. Other ARV regimens were associated with a 1.80- to 3.19-fold increase in the risk of treatment discontinuation due to ADR (P < 0.0001 for all comparisons).ABC/3TC/NVP as a simplification regimen is a long-term effective regimen with lower discontinuation due to long-term toxicity compared with other standard ARV regimens.