Changes in Sexual Behaviors in Men Who Have Sex with Men: A Comparison Between the Double-Blind and Open-Label Extension Phases of the ANRS-IPERGAY Trial.

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

Becoming adherent to a preventive treatment for HIV: a qualitative approach.

The clinical trial ANRS-IPERGAY investigated the efficacy of sexual activity-based (i.e. on demand) HIV pre-exposure prophylaxis (PrEP). Using a qualitative method, we analysed the role of adherence as one of the main elements for PrEP effectiveness and its associated determinants. Data were collected in various French ANRS-IPERGAY sites during the double-blind (2012-2014) and open-label study (2015-2016) phases, through two individual interviews per participant, collective interviews and focus groups. A total of 83 participants participated in the present study. Our analysis included 32 individual interviews (with 16 participants), 13 collective interviews (n = 45) and 8 focus groups (n = 33). We investigated adherence to on-demand pill-intake schedule, focusing especially on PrEP integration into daily life. PrEP intake was regulated through coping strategies to simplify implementation and avoid stigmatizing reactions. We considered self-care and pharmaceuticalization of prevention as specific features of sexual activity-based PrEP. As PrEP is a prophylaxis for seronegative people, it is contributing to the emergence of a new identity in the HIV field. Health-care professionals should take into account the practical implementation of PrEP schedules into daily life, assist PrEP users in personal management of pill intake and, more generally, improve adherence to the prophylaxis.

A generalized additive model to disentangle age and diagnosis-specific cohort effects in psychological and behavioral outcomes in people living with HIV: the French cross-sectional ANRS-VESPA2 survey.

BACKGROUND: Unlike their younger counterparts, some of today's older HIV patients were diagnosed before the advent of highly active antiretroviral therapy (HAART). The psychosocial and behavioral outcomes of people living with HIV (PLWH) have been widely studied, and associated factors are well known. However, their evolution both in terms of age and diagnosis-specific cohort effects is not well understood. METHODS: Data from the ANRS-VESPA2 cross-sectional survey, representative of French PLWH, were used to investigate whether psychosocial and behavioral outcomes such as quality of life, need for support and HIV status disclosure, evolve under both the influence of patients' age and diagnosis-specific cohort effects. A semi-parametric generalized additive model (GAM) was employed. The physical and mental components of health-related quality of life, the need for material and moral support, and HIV-status disclosure, constituted our outcomes. RESULTS: Non-linear diagnosis-specific cohort effects were found for physical and mental QoL and HIV-status disclosure. Overall, physical QoL was better in recently diagnosed patients than in those diagnosed in the early 1980s. An increasing influence of diagnosis-specific cohort effects between 1983 and 1995 was observed. No cohort effects were noticeable between 1996 and 2000, while an increasing influence was apparent for patients diagnosed with HIV from 2000 to 2011 (year of study). For mental QoL, the only increase was observed in participants diagnosed with HIV between 1983 and 2000. The relationship between diagnosis-specific cohort effects and HIV status disclosure was negative overall: participants diagnosed after 2000 were much less likely to disclose than those diagnosed before 1995. The effect of age was significantly associated with all outcomes, with a non-linear influence on mental QoL and with the need for material/moral support. CONCLUSIONS: Psychosocial and behavioral outcomes are complex processes which can be explained in different ways by a combination of the clinical and social contexts which PLWH are exposed to at the time of diagnosis, and by developmental characteristics. A greater understanding of these processes could inform healthcare policy-making for specific HIV generations and different HIV age groups.

Sex work among female workers in the traditional mining sector in Mali - results from the ANRS-12339 Sanu Gundo cross-sectional study in 2015.

Female sex workers (FSW) in mining sites are considered to be at very high risk of HIV infection. We aimed to characterize FSW at the Kôkôyô artisanal gold mining site in Mali, and identify factors associated with sex work using data from ANRS-12339 Sanu Gundo, a cross-sectional survey conducted in 2015 at the mine by ARCAD-SIDA, a Malian non-governmental organisation. People attending HIV-prevention activities were invited to participate in the quantitative and qualitative parts of the survey. A probit logistic regression was used for data analysis. Of 101 women who participated in the survey, 26.7% reported sex work as their main activity. Multivariate analysis showed that the probability of sex work as a main activity decreased by 1% per 1-year age increase (p = 0.020). Sex work was significantly more likely to be reported by single, divorced and widowed women (25.4% probability; p = 0.007). FSW were significantly more likely to be non-Malian (36.3% probability; p = 0.003), more likely to have a secondary activity (77% probability; p = 0.002), to work fewer than 56h/week (40.2% probability; p = 0.001) and to be in good health (12.1% probability; p = 0.016). In addition, being aware of the existence of sexually transmitted infection, using psychoactive substances, and having unprotected receptive anal sex during the previous six months were significantly associated with sex work (50.2%; p = 0.006; 45.6%, p = 0.003; and 7.4%, p = 0.016 probability, respectively). Qualitative findings confirm that poverty and boyfriends' refusal to use condoms remain key barriers to systematic condom use among FSW.

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

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

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

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

Treatment interruption in HIV-positive patients followed up in Cameroon's antiretroviral treatment programme: individual and health care supply-related factors (ANRS-12288 EVOLCam survey).

INTRODUCTION: Decreasing international financial resources for HIV and increasing numbers of antiretroviral treatment (ART)-treated patients may jeopardise treatment continuity in low-income settings. Using data from the EVOLCam ANRS-12288 survey, this study aimed to document the prevalence of unplanned treatment interruption for more than 2 consecutive days (TI>2d) and investigate the associated individual and health care supply-related factors within the Cameroonian ART programme. METHODS: A cross-sectional mixed methods survey was carried out between April and December 2014 in 19 HIV services of the Centre and Littoral regions. A multilevel logistic model was estimated on 1885 ART-treated patients in these services to investigate factors of TI>2d in the past 4 weeks. RESULTS: Among the study population, 403 (21%) patients reported TI>2d. Patients followed up in hospitals reporting ART stock-outs were more likely to report TI>2d while those followed up in the Littoral region, in medium- or small-sized hospitals and in HIV services proposing financial support were at lower risk of TI>2d. The following individual factors were also associated with a lower risk of TI>2d: living in a couple, having children, satisfaction with attention provided by doctor, tuberculosis co-infection and not having consulted a traditional healer. CONCLUSIONS: Besides identifying individual factors of TI>2d, our study highlighted the role of health care supply-related factors in shaping TI in Cameroon's ART programme, especially the deleterious effect of ART stock-outs. Our results also suggest that the high proportion of patients reporting TI could jeopardise progress in the fight against HIV in the country, unless effective measures are quickly implemented like ensuring the continuity of ART supply.

Assessement of Awareness of, Concerns and Attitudes Towards HIV-Related Court-Case Sentences in France in a Representative Sample of People Living with HIV (ANRS VESPA2 Survey).

Some of the 12 criminal trials and sentences in France for HIV transmission in 1998-2011 attracted substantial public attention, with a possible negative impact on people living with HIV (PLWH) through reinforced stigma and discrimination. This analysis aimed to characterize PLWH enrolled in the representative ANRS-VESPA2 survey, aware of and concerned about convictions for HIV transmission. Being a migrant from Sub-Saharan Africa, having difficult socio-economic conditions, having unprotected sex with one's main partner and concealing one's HIV status were all factors statistically associated with concern about the sentences. Participants tempted to press charges against someone for infecting them were more likely to be younger, women, not living in a couple, unemployed, and to report a major depressive disorder. Concern about HIV-related criminal proceedings among the most vulnerable PLWH do not reflect the actual risk of prosecution they are exposed to.

Acceptability of HIV cure-related trials: the challenges for physicians and people living with HIV (ANRS-APSEC).

Essential HIV cure-related clinical trials (HCRCT) have a potentially high-risk profile in terms of participants' health, which could hinder enrollment by people living with HIV (PLWH) and healthcare professionals (HP). The ANRS-APSEC survey is part of the IAS "Towards an HIV cure" initiative, which promotes multidisciplinary research for a safe, affordable and scalable cure. The study objectives were to understand the psychosocial mechanisms underlying PLWH and HP viewpoints about future HCRCT. Six focus group discussions (three with PLWH (n = 21) and three with HP (n = 30)) were held in three French infectious disease units. From these, three perspectives on HCRCT were identified. The first involved beliefs and knowledge associating HCRCT with poorer health and quality of life for PLWH. The second concerned perceptions of HCRCT as a biological and epidemiological flashback to a situation when HIV infection was left uncontrolled. The third was characterized by aspects of historical HIV culture that embrace innovation.

The ANRS-Ipergay trial, an opportunity to use qualitative research to understand the perception of the "participant"-physician relationship.

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.

Population Pharmacokinetic Modeling of Tenofovir in the Genital Tract of Male HIV-Infected Patients.

The aims of this study were to describe the blood plasma (BP) and seminal plasma (SP) pharmacokinetics of tenofovir (TFV) in HIV-1-infected men, to assess the role of genetic polymorphism in the variability of TFV transfer into the male genital tract, and to evaluate the impact of TFV SP exposure on seminal plasma HIV load (spVL). Men from the Evarist-ANRS EP 49 study treated with TFV as part of their antiretroviral therapy were included in the study. A total of 248 and 217 TFV BP and SP concentrations from 129 men were available for the analysis. For pharmacogenetic assessment, a total of 121 single nucleotide polymorphisms (SNP) were genotyped. Data were analyzed using a nonlinear mixed-effects modeling approach. TFV pharmacokinetics were best described by a two-compartment model for BP and by an effect compartment with different input and output constants for SP. TFV exposures (area under the concentration-time curve from 0 to 24 h [AUC0-24]) were higher in SP than in BP (median AUC0-24, 7.01 versus 2.97 mg · liter-1 · h, respectively). The median (range) SP-to-BP AUC0-24 ratio was 2.24 (0.53 to 34.13). After correction for multiple testing, none of the SNPs were significantly associated with the TFV transfer rate constant. The impact of the TFV SP AUC0-24 or TFV SP-to-BP AUC0-24 ratio on spVL was not significant (P = 0.808 and 0.768, respectively). This is the first population model describing TFV pharmacokinetics in the male genital tract. TFV SP concentrations were higher than BP concentrations. Despite TFV SP exposures being higher than BP exposures, an spVL was detectable for 12.2% of the men.

Disclosure of HIV Status Beyond Sexual Partners by People Living with HIV in France: A Call for Help? Results from the National Cross-Sectional Survey ANRS-VESPA2.

HIV status disclosure remains a complex issue for most people living with HIV (PLWH). We analyzed PLWH disclosure behaviors in France, where treatment is free and where the social image of HIV has improved in the general population. Analyses focused on disclosure to the social network excluding sexual partners (close family, other relatives, friends, colleagues). The study sample comprised 3016 participants from the nationally representative survey ANRS-VESPA2. Three PLWH clusters were identified using hierarchical classification ("high disclosure level": 28.2 %, "medium disclosure level": 27.5 %, and "low disclosure level": 44.3 %). In multivariable analyses, the variable "not living in a couple but psychological social support needed" was independently associated with medium (AOR [95 % CI] 1.8 [1.4; 2.3]) and high levels of disclosure (1.4 [1.1; 1.8]) (multinomial regression models). For PLWH living alone, HIV status disclosure may reveal a need for psychological social support, a key component to treatment adherence and positive prevention.

HIV-1-RNA in seminal plasma correlates with detection of HIV-1-DNA in semen cells, but not with CMV shedding, among MSM on successful antiretroviral regimens.

OBJECTIVES: Intermittent seminal HIV-RNA detection can occur in MSM despite concomitant plasma virological control on combined ART (cART). We undertook the present study to determine if seminal HIV detection was associated with seminal cytomegalovirus (CMV) detection or detection of HIV-infected cells in semen. METHODS: Longitudinal semen samples from HIV-1-infected MSM on successful cART enrolled in the EVARIST ANRS EP 49 study were analysed. We first conducted a case-control analysis (ratio 1 : 3) to assess HIV-DNA detection in semen cells in the 20 patients with detectable HIV-RNA in seminal plasma (cases) matched with 60 participants with undetectable HIV-RNA (controls) based on total HIV-DNA load in blood cells. Second, we measured CMV-DNA in all seminal plasma samples. RESULTS: HIV-1-DNA in semen cells was detected on at least one sample visit in 12/20 cases and 11/60 controls. Detection of HIV-RNA in seminal plasma was associated significantly with the detection of HIV-DNA in semen cells [OR, 7.6 (95% CI, 2.1-28.4); P = 0.002] when adjusted on total HIV-DNA in blood cells. CMV-DNA was detected in 107/273 seminal plasma samples with a median value of 3.62 log10 copies/mL (IQR, 2.83-4.38), yielding a prevalence of 39.2%. Seminal CMV-DNA shedding [OR, 1.5 (95% CI, 0.6-3.6); P = 0.343] was not associated with the risk of detection of HIV-RNA in seminal plasma. CONCLUSIONS: The presence of HIV-DNA in semen cells was predictive of HIV-RNA detection, suggesting that viral particles arise through local HIV replication by infected semen cells. Despite virological control, compartmentalization of HIV in the genital tract might act in residual replication and transmission.

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

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

Emtricitabine seminal plasma and blood plasma population pharmacokinetics in HIV-infected men in the EVARIST ANRS-EP 49 study.

We aimed to describe blood plasma (BP) and seminal plasma (SP) pharmacokinetics of emtricitabine (FTC) in HIV-1-infected men, assess its penetration in the male genital tract, and evaluate its impact on seminal plasma HIV load (spVL) detection. Men from the EVARIST ANRS EP49 study receiving combined antiretroviral therapy with FTC and with suppressed BP viral load were included in the study. A total of 236 and 209 FTC BP and SP concentrations, respectively, were available. A population pharmacokinetic model was developed with Monolix 4.1.4. The impact of FTC seminal exposure on spVL detection was explored by receiver operating characteristic (ROC) curves and mixed-effects logistic regressions. FTC BP pharmacokinetics was described by a two-compartment model. The addition of an effect compartment with different input and output constants best described FTC SP pharmacokinetics. No covariates were found to explain the variability in SP. FTC exposures (area under the concentration-time curve from 0 to 24 h [AUC0-24]) were higher in SP than in BP (median AUC0-24, 38.04 and 12.95 mg · liter(-1) · h, respectively). The median (range) SP-to-BP AUC0-24 ratio was 2.91 (0.84 to 10.08). Less than 1% of FTC AUC0-24 ratios were lower than 1. The impact of FTC SP AUC0-24 or FTC SP-to-BP AUC0-24 ratio on spVL detection was not significant (P = 0.943 or 0.893, respectively). This is the first population model describing FTC pharmacokinetics simultaneously in both BP and SP. FTC distributes well in the male genital tract with higher FTC concentrations in SP than in BP. FTC seminal plasma exposures were considered efficient in the majority of men.

Comparison of risk factors in HIV-infected men who have sex with men, coinfected or not with hepatitis C virus (ANRS VESPA2 French cross-sectional national survey).

OBJECTIVES: HIV-infected men who have sex with men (HIV-MSM) are at high risk of hepatitis C virus (HCV) infection. This study aimed to compare risk factors between HIV-MSM coinfected with HCV and those who are not, in a national representative survey conducted in France. METHODS: The ANRS VESPA2 survey (April 2011-January 2012) collected sociodemographic and behavioural data (through face-to-face administered questionnaires) as well as medical data (physician questionnaire) among 3022 HIV-infected adults recruited in 73 French HIV hospital departments. We identified behavioural correlates of HCV coinfection among sexually active HIV-MSM who participated in VESPA2 (logistic regression models). RESULTS: Ninety-three of the 1037 HIV-MSM of the study population (8.9%) were coinfected with HCV. The following risk factors were independently associated with HCV coinfection, after adjustment for age and time since HIV diagnosis: current or past injecting drug use, having had at least 20 male sexual partners during the previous 12 months, reporting inconsistent condom use during anal sex with casual partners, and attending sex parties. Individuals reporting at least three sexual risk factors were at the highest risk of being coinfected with HCV (OR (95% CI): 22.86 (9.74; 53.62), p<0.0001). CONCLUSIONS: HIV-MSM reporting several sexual risk factors should be sensitised to risk-reduction behaviours to avoid HCV transmission to sexual partners, and infection or reinfection with HCV.

HIV-1 DNA levels in peripheral blood mononuclear cells and cannabis use are associated with intermittent HIV shedding in semen of men who have sex with men on successful antiretroviral regimens.

BACKGROUND: Few data exist on the efficacy of combined antiretroviral therapy (cART) in semen of human immunodeficiency virus type 1 (HIV-1) infected men who have sex with men (MSM) with sustained control of HIV replication in blood. METHODS: HIV-1 infected MSM on successful cART for >6 months were enrolled. HIV-RNA was quantified in seminal plasma (spVL) and in blood plasma (bpVL) from 2 paired samples collected 4 weeks apart. Relationship between spVL and bpVL (measured by an ultrasensitive assay, LOQ 10 copies/mL), total peripheral blood mononuclear cells (PBMC)-associated HIV-DNA, sexually transmitted infections (STIs), and self-reported socio-behavioral characteristics was assessed using GEE logistic regression. RESULTS: In total, 157 patients were included. Median time with bpVL <50 copies/mL was 3.3 years. spVL was detectable in 23/304 samples (prevalence 7.6%). Median spVL was 145 cp/mL (100-1475). spVL was detectable on the first, on the second, and on both samples in 5, 14, and 2 men, respectively. In sum, 33 individuals (21%) had STIs (asymptomatic in 24/33). Residual bpVL was undetectable by ultrasensitive assay in 225/300 samples (75%). After multivariable adjustments, PBMC-associated HIV-DNA (OR 2.6[1.2; 6.0], for HIV-DNA > 2.5 log10 cp/10(6) PBMC, P = .02), and cannabis use during sexual intercourse (OR 2.8[1.2; 6.7], P = .02) were the only factors associated significantly with spVL. CONCLUSION: We show that HIV-RNA can be detected intermittently in semen of HIV-1 infected MSM despite successful cART. The size of blood HIV-1 reservoir predicted spVL detection. Our results indicated also that the possible effect of cannabis should be taken into account when developing prevention interventions targeted toward HIV-infected MSM on successful cART.

Health-related quality of life of people living with HIV followed up in hospitals in France: comparing trends and correlates between 2003 and 2011 (ANRS-VESPA and VESPA2 national surveys).

In recent years, France has witnessed both structural changes in the population of people living with HIV and a relative improvement in the social representation of HIV infection. However, potential changes in people's day-to-day experience with HIV have not been documented. We used data from the national surveys ANRS-VESPA (2003) and VESPA2 (2011) to compare the levels and patterns of correlates of health-related quality of life (HRQL) in adult HIV-infected patients followed up in French hospitals over a period of eight years. Mean physical and mental SF-12 scores were compared (VESPA, n = 2072; and VESPA2, n = 2267) using analysis of variance (ANOVA) F tests. Heckman regression models were then used to identify independent correlates of physical and mental quality of life in the two surveys, while accounting for possible bias due to missing score values. A common set of potential socio-demographic, clinical, behavioral, and psychosocial correlates was tested. Individuals reported a decrease in physical quality of life in VESPA2 compared with VESPA (mean score (standard error): 47.5 (0.2) versus 49.6 (0.2), p < .0001), and better mental HRQL (44.3 (0.3) versus 42.3 (0.3), p < 0.0001). In both surveys, financial difficulties and patient-perceived experience of rejection behaviors by medical staff were independently associated with impaired physical and mental quality of life. Older age and unemployment were independently associated with impaired physical quality of life. Immigrants from Sub-Saharan Africa reported better mental quality of life. Findings show that quality of life levels in adult HIV-infected patients followed up at hospital in France has significantly, yet modestly, changed in recent years. However, the pattern of quality of life correlates has remained relatively stable. The impact of patient-provider relationships on self-reported outcomes is confirmed. Further research is needed to identify potential differences in quality of life correlates in specific subgroups of patients, such as men who have sex with men, women, immigrants, and injecting drug users.

The virophage as a unique parasite of the giant mimivirus.

Viruses are obligate parasites of Eukarya, Archaea and Bacteria. Acanthamoeba polyphaga mimivirus (APMV) is the largest known virus; it grows only in amoeba and is visible under the optical microscope. Mimivirus possesses a 1,185-kilobase double-stranded linear chromosome whose coding capacity is greater than that of numerous bacteria and archaea1, 2, 3. Here we describe an icosahedral small virus, Sputnik, 50 nm in size, found associated with a new strain of APMV. Sputnik cannot multiply in Acanthamoeba castellanii but grows rapidly, after an eclipse phase, in the giant virus factory found in amoebae co-infected with APMV4. Sputnik growth is deleterious to APMV and results in the production of abortive forms and abnormal capsid assembly of the host virus. The Sputnik genome is an 18.343-kilobase circular double-stranded DNA and contains genes that are linked to viruses infecting each of the three domains of life Eukarya, Archaea and Bacteria. Of the 21 predicted protein-coding genes, eight encode proteins with detectable homologues, including three proteins apparently derived from APMV, a homologue of an archaeal virus integrase, a predicted primase-helicase, a packaging ATPase with homologues in bacteriophages and eukaryotic viruses, a distant homologue of bacterial insertion sequence transposase DNA-binding subunit, and a Zn-ribbon protein. The closest homologues of the last four of these proteins were detected in the Global Ocean Survey environmental data set5, suggesting that Sputnik represents a currently unknown family of viruses. Considering its functional analogy with bacteriophages, we classify this virus as a virophage. The virophage could be a vehicle mediating lateral gene transfer between giant viruses.

Structural studies of the giant mimivirus.

Mimivirus is the largest known virus whose genome and physical size are comparable to some small bacteria, blurring the boundary between a virus and a cell. Structural studies of Mimivirus have been difficult because of its size and long surface fibers. Here we report the use of enzymatic digestions to remove the surface fibers of Mimivirus in order to expose the surface of the viral capsid. Cryo-electron microscopy (cryoEM) and atomic force microscopy were able to show that the 20 icosahedral faces of Mimivirus capsids have hexagonal arrays of depressions. Each depression is surrounded by six trimeric capsomers that are similar in structure to those in many other large, icosahedral double-stranded DNA viruses. Whereas in most viruses these capsomers are hexagonally close-packed with the same orientation in each face, in Mimivirus there are vacancies at the systematic depressions with neighboring capsomers differing in orientation by 60 degrees . The previously observed starfish-shaped feature is well-resolved and found to be on each virus particle and is associated with a special pentameric vertex. The arms of the starfish fit into the gaps between the five faces surrounding the unique vertex, acting as a seal. Furthermore, the enveloped nucleocapsid is accurately positioned and oriented within the capsid with a concave surface facing the unique vertex. Thus, the starfish-shaped feature and the organization of the nucleocapsid might regulate the delivery of the genome to the host. The structure of Mimivirus, as well as the various fiber components observed in the virus, suggests that the Mimivirus genome includes genes derived from both eukaryotic and prokaryotic organisms. The three-dimensional cryoEM reconstruction reported here is of a virus with a volume that is one order of magnitude larger than any previously reported molecular assembly studied at a resolution of equal to or better than 65 Angstroms.