Hepatitis B prevention and treatment needs in women in Senegal (ANRS 12356 AmBASS survey).

BACKGROUND: Although mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is prevalent in West Africa, epidemiological data on HBV infection in women remain scarce. We studied i) hepatitis B surface antigen (HBsAg) prevalence and its correlates, ii) HBV screening history and serological status awareness, iii) MTCT risk and treatment needs in Senegalese women. METHODS: A cross-sectional population-based serosurvey for HBsAg positivity was conducted in 2018-2019 in the rural area of Niakhar (Fatick region, Senegal). Participants were offered home-based HBV screening and answered face-to-face questionnaires. HBsAg-positive participants underwent clinical and biological assessments. Data were weighted and calibrated to be representative of the area's population. Logistic regression models helped identify factors associated with HBsAg-positivity in adult women (> 15 years old). RESULTS: HBsAg prevalence in adult women was 9.2% [95% confidence interval: 7.0-11.4]. Factors associated with HBsAg-positivity were being 15-49 years old (ref: ≥ 50), living in a household with > 2 other HBsAg-positive members, and knowing someone with liver disease. Only 1.6% of women had already been tested for HBV; no one who tested HBsAg positive was already aware of their serological status. In women 15-49 years old, 5% risked MTCT and none were eligible for long-term antiviral treatment. CONCLUSIONS: Adult women have a high HBsAg prevalence but a low MTCT risk. Low rates of HBV screening and serological status awareness argue for the adoption of systematic screening during pregnancy using free and rapid diagnostic tests. Additionally, screening household members of HBsAg-positive women may greatly improve the cascade of care in rural Senegal. TRIAL REGISTRATION: ClinicalTrials.gov identifier (NCT number): NCT03215732.

Elevated Fatty Liver Index as a Risk Factor for All-Cause Mortality in Human Immunodeficiency Virus-Hepatitis C Virus-Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study).

BACKGROUND AND AIMS: Human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients are at high risk of metabolic complications and liver-related events, which are both associated with hepatic steatosis and its progressive form, nonalcoholic steatohepatitis, a known risk factor for mortality. The fatty liver index (FLI), a noninvasive steatosis biomarker, has recently drawn attention for its clinical prognostic value, although its capacity to predict mortality risk in HIV-HCV-coinfected patients has never been investigated. Using a Cox proportional hazards model for mortality from all causes, with data from the French National Agency for Research on Aids and Viral Hepatitis CO13 HEPAVIH cohort (983 patients, 4,432 visits), we tested whether elevated FLI (≥60) was associated with all-cause mortality. APPROACH AND RESULTS: After multiple adjustment, individuals with FLI ≥ 60 had almost double the risk of all-cause mortality (adjusted hazard ratio [95% confidence interval], 1.91 [1.17-3.12], P = 0.009), independently of the following factors: HCV cure (0.21 [0.07-0.61], P = 0.004), advanced fibrosis (1.77 [1.00-3.14], P = 0.05), history of hepatocellular carcinoma and/or liver transplantation (7.74 [3.82-15.69], P < 10-3 ), history of indirect clinical signs of cirrhosis (2.80 [1.22-6.41], P = 0.015), and HIV Centers for Disease Control and Prevention clinical stage C (2.88 [1.74-4.79], P < 10-3 ). CONCLUSIONS: An elevated FLI (≥60) is a risk factor for all-cause mortality in HIV-HCV-coinfected patients independently of liver fibrosis and HCV cure. In the present era of nearly 100% HCV cure rates thanks to direct-acting antivirals, these findings encourage the more systematic use of noninvasive steatosis biomarkers to help identify coinfected patients with higher mortality risk.

HCV Cure and Cannabis Abstinence Facilitate Tobacco Smoking Quit Attempts in HIV-HCV Co-Infected Patients (ANRS CO13 HEPAVIH Cohort Study).

In Western countries, tobacco smoking is highly prevalent among patients co-infected with HIV and hepatitis C virus (HCV). In the era of antiretrovirals and HCV cure, smoking-related health damages contribute greatly to morbidity and mortality in HIV-HCV co-infected patients. We used longitudinal data from the ANRS CO13 HEPAVIH cohort to identify the correlates of tobacco smoking quit attempts (TSQA) in HIV-HCV co-infected patients. TSQA were modelled using a multivariable discrete-time Cox proportional hazards model in 695 HIV-HCV co-infected tobacco smokers. HCV cure was associated with a 76% higher chance of TSQA (adjusted hazard ratio [95% confidence interval]: 1.76 [1.06-2.93], p = 0.029), and cannabis use with a 37% lower chance (0.63 [0.40-1.00], p = 0.049), independently of the mode of HIV transmission, other psychoactive substance use, and body mass index. Patients should be screened for tobacco and cannabis use at HCV treatment initiation and during follow-up. They should also be provided with comprehensive counselling and referral to addiction services. Non-smoking routes of cannabis administration should be promoted for cannabis users who wish to quit smoking tobacco.

HCV-Related Mortality Among HIV/HCV Co-infected Patients: The Importance of Behaviors in the HCV Cure Era (ANRS CO13 HEPAVIH Cohort).

Mortality among individuals co-infected with HIV and hepatitis C virus (HCV) is relatively high. We evaluated the association between psychoactive substance use and both HCV and non-HCV mortality in HIV/HCV co-infected patients in France, using Fine and Gray's competing-risk model adjusted for socio-demographic, clinical predictors and confounding factors, while accounting for competing causes of death. Over a 5-year median follow-up period, 77 deaths occurred among 1028 patients. Regular/daily cannabis use, elevated coffee intake, and not currently smoking were independently associated with reduced HCV-mortality (adjusted sub-hazard ratio [95% CI] 0.28 [0.10-0.83], 0.38 [0.15-0.95], and 0.28 [0.10-0.79], respectively). Obesity and severe thinness were associated with increased HCV-mortality (2.44 [1.00-5.93] and 7.25 [2.22-23.6] versus normal weight, respectively). Regular binge drinking was associated with increased non-HCV-mortality (2.19 [1.10-4.37]). Further research is needed to understand the causal mechanisms involved. People living with HIV/HCV co-infection should be referred for tobacco, alcohol and weight control interventions and potential benefits of cannabis-based therapies investigated.

Prevention and care of hepatitis B in the rural region of Fatick in Senegal: a healthcare workers' perspective using a mixed methods approach.

BACKGROUND: In countries where hepatitis B virus (HBV) is endemic, including Senegal, the World Health Organization recommends systematic HBV screening of pregnant women and vaccination at birth to prevent mother-to-child transmission (MTCT). This study investigated healthcare workers' (HCW) knowledge and practices regarding HBV prevention and care in the rural region of Fatick in Senegal, as well as challenges they faced in implementing prevention activities related to HBV MTCT. METHODS: A mixed-methods survey was conducted between May-July 2017 among 112 HCW working in 15 healthcare facilities in two districts of the Fatick region using face-to-face questionnaires and semi-structured interviews. Descriptive statistics and chi-square/Mann-Whitney tests were used to analyze quantitative data, while qualitative data were analyzed thematically. RESULTS: The study population included 87 HCW in the quantitative component (83% women, median age [interquartile range, IQR] = 35 [31-40] years) and 11 in the qualitative component. A knowledge gap was observed in key areas of HBV infection: only 24, 51 and 38%, respectively, correctly reported that early HBV acquisition is associated with a high risk of developing chronic infection, that perinatal transmission is one of the main modes of HBV transmission in Senegal, and that three to four doses of HBV vaccine are required to ensure immunization in children. Despite good acceptability of systematic screening of pregnant women and vaccination at birth, only 48% of HCW mainly involved in prenatal care and 71% of those involved exclusively in vaccination routinely performed these two key interventions. HCW reported several structural barriers that may hinder their implementation: a lack of training in HBV and in counseling, poor availability of rapid diagnostic tests (RDT), high costs of both screening and treatment, a lack of adequate information on treatment options and missed opportunities for vaccination at birth. CONCLUSIONS: HCW working in the Fatick region may be insufficiently trained and supported to effectively implement HBV prevention strategies. Our findings suggest an urgent need to strengthen MTCT prevention in this region, by improving HCW knowledge in key areas of HBV infection, providing RDT and antiviral treatment at low cost, and enhancing community-based interventions for the timely vaccination of newborns.

B-cell non-Hodgkin lymphoma linked to Coxiella burnetii.

Bacteria can induce human lymphomas, whereas lymphoproliferative disorders have been described in patients with Q fever. We observed a lymphoma in a patient with Q fever that prompted us to investigate the association between the 2 diseases. We screened 1468 consecutive patients of the 2004 to 2014 French National Referral Center for Q fever database. The standardized incidence ratios (SIRs) of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were calculated comparatively to the 2012 Francim Registry. The presence of Coxiella burnetii was tested using immunofluorescence and fluorescence in situ hybridization using a specific 16S ribosomal RNA probe and genomic DNA probe. Seven patients (0.48%) presented mature B-cell lymphoma consisting of 6 DLBCL and 1 FL. An excess risk of DLBCL and FL was found in Q fever patients compared with the general population (SIR [95% confidence interval], 25.4 [11.4-56.4] and 6.7 [0.9-47.9], respectively). C burnetii was detected in CD68(+) macrophages within both lymphoma and lymphadenitis tissues but localization in CD123(+) plasmacytoid dendritic cells (pDCs) was found only in lymphoma tissues. Q fever patients with persistent focalized infection were found more at risk of lymphoma (hazard ratio, 9.35 [1.10-79.4]). Interleukin-10 (IL10) overproduction (P = .0003) was found in patients developing lymphoma. These results suggest that C burnetii should be added to the list of bacteria that promote human B-cell non-Hodgkin lymphoma, possibly by the infection of pDCs and IL10 overproduction. Screening for early lymphoma diagnosis should be considered in the management of patients with Q fever, especially those with persistent focalized infections.

Protective effect of coffee consumption on all-cause mortality of French HIV-HCV co-infected patients.

BACKGROUND & AIMS: Coffee has anti-inflammatory and hepato-protective properties. In the general population, drinking ≥3cups of coffee/day has been associated with a 14% reduction in the risk of all-cause mortality. The aim of this study was to investigate the relationship between coffee consumption and the risk of all-cause mortality in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). METHODS: ANRS CO13 HEPAVIH is an ongoing French nationwide prospective cohort of patients co-infected with HIV-HCV collecting both medical and psychosocial/behavioural data (annual self-administered questionnaires). We used a Cox proportional hazards model to estimate the effect of elevated coffee consumption (≥3cups/day) at baseline on all-cause mortality during the cohort's five-year follow-up. RESULTS: Over a median [interquartile range] follow-up of 5.0 [3.9-5.9] years, 77 deaths occurred among 1,028 eligible patients (mortality rate 1.64/100 person-years; 95% confidence interval [CI] 1.31-2.05). Leading causes of death were HCV-related diseases (n=33, 43%), cancers unrelated to AIDS/HCV (n=9, 12%), and AIDS (n=8, 10%). At the first available visit, 26.6% of patients reported elevated coffee consumption. Elevated coffee consumption at baseline was associated with a 50% reduced risk of all-cause mortality (hazard ratio 0.5; CI 0.3-0.9; p=0.032), after adjustment for gender and psychosocial, behavioral and clinical time-varying factors. CONCLUSIONS: Drinking three or more cups of coffee per day halves all-cause mortality risk in patients co-infected with HIV-HCV. The benefits of coffee extracts and supplementing dietary intake with other anti-inflammatory compounds need to be evaluated in this population. LAY SUMMARY: Coffee has anti-inflammatory and hepato-protective properties but its effect on mortality risk has never been investigated in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). This study shows that elevated coffee consumption (≥3cups/day) halves all-cause mortality risk in patients co-infected with HIV-HCV. The benefits of coffee extracts and supplementing dietary intake with other anti-inflammatory compounds need to be evaluated in this population.

The impact of ledipasvir/sofosbuvir on patient-reported outcomes in cirrhotic patients with chronic hepatitis C: the SIRIUS study.

BACKGROUND: Interferon- and ribavirin (RBV)-free regimens can improve patient-reported outcomes (PROs) during treatment. AIM: To compare PROs during treatment with ledipasvir and sofosbuvir (LDV/SOF) to placebo and to LDV/SOF + RBV. METHODS: Treatment-experienced CH-C genotype 1 patients with compensated cirrhosis (N = 154) were randomized to receive 24 weeks of LDV/SOF or 12 weeks of placebo followed by 12 weeks of LDV/SOF + RBV (the SIRIUS clinical trial). While blinded to their HCV RNA level and study treatment, patients completed PRO questionnaires (SF-36, FACIT-F, CLDQ-HCV, WPAI:SHP) at baseline, during and post-treatment. RESULTS: Baseline PRO scores were similar between the two study arms. Patients receiving LDV/SOF showed improvement in a number of PROs (predominantly related to mental health) starting as early as 4 weeks after treatment initiation; no PRO decrement from baseline were noted, and no PRO scores were inferior to placebo (all P > 0.05). In the second 12 weeks, patients who were receiving LDV/SOF continued to improve PROs (up to +9.2% from a 100% maximum possible score, P < 0.05), while patients receiving LDV/SOF + RBV had less gains or no improvement in their PRO scores. However, regardless of the regimen, patients who successfully cleared the virus (N = 149) had significant improvement in all aspects of PROs (up to +12.2% by post-treatment week 12, up to +16.9% by week 24). CONCLUSIONS: Treatment-experienced cirrhotic patients experience a notable improvement of their PROs during treatment with LDV/SOF. Furthermore, achieving SVR-12 is associated with significant PRO improvement, which further improves at post-treatment week 24 in this difficult to treat group of patients with chronic hepatitis C.

Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients: A Longitudinal Analysis (ANRS CO13 HEPAVIH).

BACKGROUND: Diabetes and insulin resistance (IR) is common in human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients, a population also concerned with elevated cannabis use. Cannabis has been associated with reduced IR risk in some population-based surveys. We determined whether cannabis use was consistently associated with reduced IR risk in HEPAVIH, a French nationwide cohort of HIV-HCV-coinfected patients. METHODS: HEPAVIH medical and sociobehavioral data were collected (using annual self-administered questionnaires). We used 60 months of follow-up data for patients with at least 1 medical visit where IR (using homeostatic model assessment of insulin resistance [HOMA-IR]) and cannabis use were assessed. A mixed logistic regression model was used to evaluate the association between IR risk (HOMA-IR > 2.77) and cannabis use (occasional, regular, daily). RESULTS: Among the 703 patients included in the study (1287 visits), 323 (46%) had HOMA-IR > 2.77 for at least 1 follow-up visit and 319 (45%) reported cannabis use in the 6 months before the first available visit. Cannabis users (irrespective of frequency) were less likely to have HOMA-IR > 2.77 (odds ratio [95% confidence interval], 0.4 [.2-.5]) after adjustment for known correlates/confounders. Two sensitivity analyses with HOMA-IR values as a continuous variable and a cutoff value of 3.8 confirmed the association between reduced IR risk and cannabis use. CONCLUSIONS: Cannabis use is associated with a lower IR risk in HIV-HCV-coinfected patients. The benefits of cannabis-based pharmacotherapies for patients concerned with increased risk of IR and diabetes need to be evaluated in clinical research and practice.

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.

Reevaluation of the risk of fetal death and malformation after Q Fever.

A meta-analysis of 136 Q fever pregnancies, including 4 new cases and 7 population-based serological studies, revealed significant increases in fetal death and malformation after Q fever during pregnancy. This poor obstetric outcome is prevented by antibiotic treatment.

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.

Prediction of HIV drug resistance based on virologic, immunologic, clinical, and/or adherence criteria in the Stratall ANRS 12110/ESTHER trial in Cameroon.

Our study in Cameroonian rural district hospitals showed that the immunologic and clinical failure criteria had poor performance to identify human immunodeficiency virus drug resistance in a timely manner. Switching to second-line antiretroviral therapy after 2 consecutive viral loads ≥5000 copies/mL, as recommended by the World Health Organization, appeared to be the most appropriate strategy.

Changes in sexual activity and risk behaviors among PLWHA initiating ART in rural district hospitals in Cameroon -- data from the STRATALL ANRS 12110/ESTHER trial.

The continued scaling-up of antiretroviral therapy (ART) in Sub-Saharan Africa provides an opportunity to further study its impact on sexual behaviors among people living with HIV/AIDS (PLWHA). We explored time trend and correlates of sexual activity among PLWHA initiating ART in Cameroon and compared sexual risk behaviors between patients sexually active before and after initiating ART and those resuming sexual activity after ART initiation. Analyses were based on longitudinal data collected within the randomized trial (n=459) conducted in nine rural district hospitals in Cameroon. Sexual activity was defined as reporting at least one sexual partner during the previous 3 months. Inconsistent condom use (ICU) was defined as reporting to have "never," "sometimes," or "nearly always" used condoms at least once with a partner(s) either HIV-negative or of unknown HIV status during the same period. Mc Nemar tests were used to assess time trend, while mixed-effect logistic regressions were conducted to analyze the effect of time since ART initiation on sexual activity. The proportion of sexually active patients significantly increased over time: from 31.8% at baseline to 40.2 and 47.1% after 6 and 12 months of ART, respectively (p=0.001), to 55.9% after 24 months (p=0.02). After adjustment for behavioral and psychosocial factors, time since ART initiation was independently associated with reporting sexual activity (AOR [95% CI]=1.30 [1.17-1.46] per 6-month increase, p=0.001). ICU was more frequent among patients sexually active both before and after ART initiation than among those who resumed sexual activity after ART initiation (82 vs. 59%, p

Positive relations between sexual quality of life and satisfaction with healthcare in women living with HIV and/or HCV: Results from a multicountry study.

INTRODUCTION: The sexual quality of life is a neglected concern in women living with HIV (WHIV) or with HCV (WHCV), which can further be affected by their experience with stigma, social instability, fear of transmission and reduced access to treatment. The objective of this study was to identify sociodemographic, psychosocial, and behavioural factors associated with sexual quality of life (SQoL) in this study group. METHODS: Between December 2017 and December 2018, PROQoL-Sex Life questionnaire was administered to 404 WHIV and WHCV in five countries. PROQoL-SQoL consists of four dimensions: positive sexual perception (Psp), stigma and social distress (Sti), soft sexual practices (Sof), sexual practices with a partner (Sp), all of which were scored from 0 to 100 and considered as main outcomes, lower scores mean better sexual quality of life. Linear mixed effects models were used to evaluate the association with sociodemographic and psychosocial factors. RESULTS: Of the participants analyzed, 191 were living with HCV, 180 with HIV and 33 with HIV and HCV, median age was 48. Among WHIV, a higher satisfaction with health care, and talking about sexuality with healthcare workers were associated with lower scores in all the dimensions of the SQoL, while psychoactive substance use was associated with lower scores of Sti and Sof. Moreover, higher satisfaction with health care, talking about sexuality with healthcare workers, and psychoactive substance use (except cocaine use) in WHCV were associated with lower scores in Psp, Sti, and Sof. Besides, cocaine use was associated with higher scores of Sof. CONCLUSION: This study highlighted strong relationship between the quality of health care, and psychoactive substance use (except cocaine) and the sexual quality of life in WHIV and WHCV in these five countries. These findings draw attention to the different interventions that can be proposed for improving the sexual quality of life.

Adherence to and effectiveness of highly active antiretroviral treatment for HIV infection: assessing the bidirectional relationship.

BACKGROUND: It is well established that high adherence to HIV-infected patients on highly active antiretroviral treatment (HAART) is a major determinant of virological and immunologic success. Furthermore, psychosocial research has identified a wide range of adherence factors including patients' subjective beliefs about the effectiveness of HAART. Current statistical approaches, mainly based on the separate identification either of factors associated with treatment effectiveness or of those associated with adherence, fail to properly explore the true relationship between adherence and treatment effectiveness. Adherence behavior may be influenced not only by perceived benefits-which are usually the focus of related studies-but also by objective treatment benefits reflected in biological outcomes. METHODS: Our objective was to assess the bidirectional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical approach based on the separate estimations of an adherence and an effectiveness equation to an econometric approach using a 2-equation simultaneous system based on the same 2 equations. RESULTS: Our results highlight a reciprocal relationship between adherence and treatment effectiveness. After controlling for endogeneity, adherence was positively associated with treatment effectiveness. Furthermore, CD4 count gain after baseline was found to have a positive significant effect on adherence at each observation period. This immunologic parameter was not significant when the adherence equation was estimated separately. In the 2-equation model, the covariances between disturbances of both equations were found to be significant, thus confirming the statistical appropriacy of studying adherence and treatment effectiveness jointly. CONCLUSIONS: Our results, which suggest that positive biological results arising as a result of high adherence levels, in turn reinforce continued adherence and strengthen the argument that patients who do not experience rapid improvement in their immunologic and clinical statuses after HAART initiation should be prioritized when developing adherence support interventions. Furthermore, they invalidate the hypothesis that HAART leads to "false reassurance" among HIV-infected patients.