Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

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.

Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus-co-infected patients (ANRS CO13-HEPAVIH).

Liver steatosis is common in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-co-infected patients. Some recent studies have found that cannabis use is negatively associated with insulin resistance in the general population and in HIV-HCV-co-infected patients. Given the causal link between insulin resistance and steatosis, we hypothesized that cannabis use has a positive impact on steatosis. Therefore, we aimed to study whether cannabis use in this population was associated with a reduced risk of steatosis, measured by ultrasound examination. ANRS CO13-HEPAVIH is a French nationwide multicentre cohort of HIV-HCV-co-infected patients. Medical and socio-behavioural data from clinical follow-up visits and annual self-administered questionnaires were prospectively collected. A cross-sectional analysis was conducted using data from the first visit where both ultrasound examination data for steatosis (positive or negative diagnosis) and data on cannabis use were available. A logistic regression model was used to evaluate the association between cannabis use and steatosis. Among study sample patients (n = 838), 40.1% had steatosis. Fourteen per cent reported daily cannabis use, 11.7% regular use and 74.7% no use or occasional use ("never or sometimes"). Daily cannabis use was independently associated with a reduced prevalence of steatosis (adjusted odds ratio [95% CI] = 0.64 [0.42;0.99]; P = .046), after adjusting for body mass index, hazardous alcohol consumption and current or lifetime use of lamivudine/zidovudine. Daily cannabis use may be a protective factor against steatosis in HIV-HCV-co-infected patients. These findings confirm the need for a clinical evaluation of cannabis-based pharmacotherapies in this population. Eudract.ema.europa.eu number, DGS050367.

Heterosexual practices of women and men living with HIV attending hospital outpatient services (ANRS-VESPA2 survey): a French comparative study with the general population (CSF survey).

HAART has improved the well-being of many people living with HIV (PLWH). This study aimed at (i) comparing heterosexual practices between PLWH and the general population by gender, and (ii) identifying factors associated with sexual practices and at-risk behaviors in the two populations. Self-reported data were collected among PLWH attending hospitals (VESPA2 survey; n = 3022) and the general population (CSF survey; n = 10,280). Significant differences between the two samples were corrected for by implementing propensity score matching on both socio-demographic characteristics and sexual behavior in terms of number of partners. Men not reporting heterosexual intercourse were excluded. After matching, 61% of women (out of 707) and 68% of men (out of 709) were sexually active in both populations. PLWH practiced oral sex less than the general population and used condoms more consistently over the previous 12-month period, irrespective of having multiple sexual partners or not. For women living with HIV: those with several sexual partners and those consuming drugs over the previous 12 months were more likely to practice oral sex; those living in a couple for at least 6 years and migrants were less likely to practice anal intercourse. For men living with HIV: those reporting bisexual relationships and those with multiple sexual partners over the previous 12 months were more likely to practice anal heterosexual intercourse; migrants reported less oral sex, irrespective of HIV status. Error term correlations showed that anal intercourse was not linked to condom use for women or men from either population. Our results show that PLWH had a lower rate of heterosexual practices compared with the general population, and used condoms more often, irrespective of the number of sexual partners and strong cultural background (e.g., for Sub-Saharan African women). Further preventive information needs to be disseminated on the risk of infection transmission through heterosexual anal intercourse.

Satisfaction with care in HIV-infected patients treated with long-term follow-up antiretroviral therapy: the role of social vulnerability.

The aim of this study was to determine factors associated with complete satisfaction with the care provided (satisfaction with physicians and satisfaction with services and organization) among HIV-infected patients followed up in the French ANRS CO8 APROCO-COPILOTE cohort. Analyses focused on cross-sectional data collected during the ninth year of cohort follow-up. Satisfaction with care, sociodemographic characteristics, and behavioral data were collected using self-administered questionnaires, while clinical data were derived from medical records. Complete satisfaction with care was defined as being 100% satisfied. Two logistic regression models were used to identify predictors of (1) complete satisfaction with physicians (n=404) and (2) complete satisfaction with services and organization (n=396). Sixteen percent of patients were completely satisfied with physicians, while 15.9% were completely satisfied with services and organization. Being older and reporting fewer discomforting antiretroviral therapy (ART) side effects were factors independently associated with complete satisfaction with both physicians and services and organization. Strong support from friends and absence of hepatitis C (HCV) co-infection were independently associated with complete satisfaction with physicians, while strong support from one's family and comfortable housing conditions were independently associated with complete satisfaction with services and organization. Even after nine years of follow-up, social vulnerabilities still strongly influence HIV-infected patients' interactions with the health care system. Day-to-day experience with the disease, including perceived treatment side effects, appears to play a key role in the quality of these interactions. More attention should be given to patient satisfaction, especially for socially vulnerable patients, in order to avoid potentially detrimental consequences such as poor adherence to ART.

Factors associated with unprotected anal intercourse among men who have sex with men in Douala, Cameroon.

OBJECTIVES: Research on men who have sex with men (MSM) in sub-Saharan Africa was neglected for a long time. The objective of this study was to understand factors associated with unprotected anal intercourse (UAI) with male partners among a group of MSM living in the city of Douala, Cameroon. METHODS: In 2008, a survey on the sexual activity and practices of MSM was set up in Douala in collaboration with a local community-based organisation. Data were collected among a convenience sample of 168 MSM during face-to-face interviews with trained interviewers. RESULTS: A total of 142 individuals reported sexual activity during the previous 6 months, among whom 80 (57%) reported UAI with male partners. In a multivariate logistic regression model adjusted for the frequency of sexual intercourse, not having had access to prevention interventions and not knowing any HIV-infected person were both independently associated with a higher risk of UAI. Other factors associated with this higher risk included having had a stable male partnership at some point in one's life and not having been out of Douala for more than 4 weeks during the previous year. CONCLUSIONS: This community-based research is the first study of MSM in Cameroon and the HIV transmission risks they face. Results show the importance of HIV prevention interventions from peers, and underline the need to maintain efforts to develop specific interventions targeting MSM more efficiently in the African context.

CD4 T cell recovery is slower in patients experiencing viral load rebounds during HAART.

To determine whether viral load rebounds during HAART impact on CD4+ T cell recovery and immune reconstitution, we studied a prospective cohort of 355 antiretroviral naive patients enrolled to be randomized in a trial of three strategies of induction/maintenance HAART. The extent of immune reconstitution in blood through 72 weeks of antiretroviral treatment was evaluated. Lymphocyte subset markers (CD4, CD8, CD45RA, CD62L, CD16, CD19), activation markers (HLA-DR, CD38, CD25) were performed by cytometry analysis. Our results showed that plasma HIV-1 RNA was suppressed to below 500 copies per ml through week 72 in 240 patients (group 1) while the remaining 115 patients experienced at least one viral rebound (group 2). At baseline, CD4 cell count was higher and HIV-1 RNA was lower in group 1 than in group 2. Over 72 weeks, mean increase in CD4+ T cell count was 0.32 cell/mm3/day in group 1 and only 0.14 cell/mm3/day in group 2 (P < 0.0001). However, the patterns of changes in CD4+ and CD8+ T cell subsets during therapy were very similar across the two groups with only subtle and very limited differences. We conclude that permanent control of HIV replication could be necessary for faster immune reconstitution.