Investigating linkage to care following community-based screening for hepatitis B virus in rural Senegal: A mixed methods study.

This paper investigates linkage to care following community-based screening for hepatitis B virus (HBV) in rural Senegal. HBV-positive participants who completed a biological and clinical examination to assess liver disease and treatment eligibility were referred to a regional hospital (if eligible for treatment), invited to join the Sen-B research cohort study (adults with detectable viral load) or referred to their local health centre (all others). Logistic regressions were conducted to investigate factors associated with (i) uptake of the scheduled post-screening examination, and (ii) HBV management initiation. Obstacles to HBV management were identified using thematic analysis of in-depth patient interviews. Of the 206 HBV-positive participants, 163 (79.1%) underwent the examination; 47 of the 163 (28.8%) initiated HBV management. Women, people not migrating for >6 months/year, individuals living in households with more agricultural and monetary resources, with other HBV-positive participants, and beneficiaries of the national cash transfer program, were all more likely to undergo the examination. The likelihood of joining the Sen-B cohort increased with household monetary resources, but decreased with agricultural resources. Initiation of HBV management in local health centre was higher among participants with a non-agricultural economic activity. Individuals reported wariness and confusion about HBV management content and rationale at various stages of the care continuum, in particular with respect to venous blood sampling and management without treatment. In conclusion, HBV community-based test-and-treat strategies are feasible, but early loss to follow-up must be addressed through simplified, affordable management and community support and sensitization.

Cost-utility analysis of four WHO-recommended sofosbuvir-based regimens for the treatment of chronic hepatitis C in sub-Saharan Africa.

BACKGROUND: Although direct-acting antivirals (DAA) have become standard care for patients with chronic hepatitis C worldwide, there is no evidence for their value for money in sub-Saharan Africa. We assessed the cost-effectiveness of four sofosbuvir-based regimens recommended by the World Health Organization (WHO) in Cameroon, Côte d'Ivoire and Senegal. METHODS: Using modelling, we simulated chronic hepatitis C progression with and without treatment in hypothetical cohorts of patients infected with the country's predominant genotypes (1, 2 and 4) and without other viral coinfections, history of liver complication or hepatocellular carcinoma. Using the status-quo 'no DAA treatment' as a comparator, we assessed four regimens: sofosbuvir-ribavirin, sofosbuvir-ledipasvir (both recommended in WHO 2016 guidelines and assessed in the TAC pilot trial conducted in Cameroon, Côte d'Ivoire and Senegal), sofosbuvir-daclatasvir and sofosbuvir-ledipasvir (two pangenotypic regimens recommended in WHO 2018 guidelines). DAA effectiveness, costs and utilities were mainly estimated using data from the TAC pilot trial. Secondary data from the literature was used to estimate disease progression probabilities with and without treatment. We considered two DAA pricing scenarios: S1) originator prices; S2) generic prices. Uncertainty was addressed using probabilistic and deterministic sensitivity analyses and cost-effectiveness acceptability curves. RESULTS: With slightly higher effectiveness and significantly lower costs, sofosbuvir/velpatasvir was the preferred DAA regimen in S1 with incremental cost-effectiveness ratios (ICERs) ranging from US$526 to US$632/QALY. At the cost-effectiveness threshold (CET) of 0.5 times the 2017 country's per-capita gross domestic product (GDP), sofosbuvir/velpatasvir was only cost-effective in Senegal (probability > 95%). In S2 at generic prices, sofosbuvir/daclatasvir was the preferred regimen due to significantly lower costs. ICERs ranged from US$139 to US$216/QALY according to country i.e. a 95% probability of being cost-effective. Furthermore, this regimen was cost-effective (probability> 95%) for all CET higher than US$281/QALY, US$223/QALY and US$195/QALY in Cameroon, Côte d'Ivoire and Senegal, respectively, corresponding to 0.14 (Côte d'Ivoire and Senegal) and 0.2 (Cameroon) times the country's per-capita GDP. CONCLUSIONS: Generic sofosbuvir/daclatasvir is very cost-effective for treating chronic hepatitis C in sub-Saharan Africa. Large-scale use of generics and an increase in national and international funding for hepatitis C treatment must be priorities for the HCV elimination agenda.

Early ART Initiation Improves HIV Status Disclosure and Social Support in People Living with HIV, Linked to Care Within a Universal Test and Treat Program in Rural South Africa (ANRS 12249 TasP Trial).

We investigated the effect of early antiretroviral treatment (ART) initiation on HIV status disclosure and social support in a cluster-randomized, treatment-as-prevention (TasP) trial in rural South Africa. Individuals identified HIV-positive after home-based testing were referred to trial clinics where they were invited to initiate ART immediately irrespective of CD4 count (intervention arm) or following national guidelines (control arm). We used Poisson mixed effects models to assess the independent effects of (a) time since baseline clinical visit, (b) trial arm, and (c) ART initiation on HIV disclosure (n = 182) and social support (n = 152) among participants with a CD4 count > 500 cells/mm3 at baseline. Disclosure and social support significantly improved over follow-up in both arms. Disclosure was higher (incidence rate ratio [95% confidence interval]: 1.24 [1.04; 1.48]), and social support increased faster (1.22 [1.02; 1.46]) in the intervention arm than in the control arm. ART initiation improved both disclosure and social support (1.50 [1.28; 1.75] and 1.34 [1.12; 1.61], respectively), a stronger effect being seen in the intervention arm for social support (1.50 [1.12; 2.01]). Besides clinical benefits, early ART initiation may also improve psychosocial outcomes. This should further encourage countries to implement universal test-and-treat strategies.

Free access to antiretroviral treatment and protection against the risk of catastrophic health expenditure in people living with HIV: evidence from Cameroon.

BACKGROUND: To foster access to care and reduce the burden of health expenditures on people living with HIV (PLHIV), several sub-Saharan African countries, including Cameroon, have adopted a policy of removing HIV-related fees, especially for antiretroviral treatment (ART). We investigate the impact of Cameroon's free antiretroviral treatment (ART) policy, enacted in May 2007, on catastrophic health expenditure (CHE) risk according to socioeconomic status, in PLHIV enrolled in the country's treatment access program. METHODS: Based on primary data from two cross-sectional surveys of PLHIV outpatients in 2006-2007 and 2014 (i.e., before and after the policy's implementation, respectively), we used inverse propensity score weighting to reduce covariate imbalances between participants in both surveys, combined with probit regressions of CHE incidence. The analysis included participants treated with ART in one of the 11 HIV services common to both surveys (n = 1275). RESULTS: The free ART policy was associated with a significantly lower risk of CHE only in the poorest PLHIV while no significant effect was found in lower-middle or upper socioeconomic status PLHIV. Unexpectedly, the risk of CHE was higher in those with middle socioeconomic status after the policy's implementation. CONCLUSIONS: Our findings suggest that Cameroon's free ART policy is pro-poor. As it only benefitted PLHIV with the lowest socioeconomic status, increased comprehensive HIV care coverage is needed to substantially reduce the risk of CHE and the associated risk of impoverishment for all PLHIV.

Cannabis use is associated with a lower risk of diabetes in chronic hepatitis C-infected patients (ANRS CO22 Hepather cohort).

Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes. In the general population, research has shown the potential benefit of cannabis use for the prevention of diabetes and related metabolic disorders. We aimed to test whether cannabis use is associated with a lower risk of diabetes in chronic HCV-infected patients. Chronic HCV-infected patients (n = 10 445) were selected from the French national, multicenter, observational ANRS CO22 Hepather cohort. Cross-sectional data collected at cohort enrollment were used to assess the association between patients' clinical and behavioural characteristics and the risk of diabetes. Logistic regression model was performed with cannabis use as the main independent variable and a significance level set at 5%. A similar model stratified by the presence of advanced liver fibrosis (FIB-4 > 3.25) was also run. After multivariable adjustment, current (AOR [95%CI]: 0.49 [0.38-0.63]) and former (0.81 [0.67-0.98], P < .001) cannabis use were both associated with a reduced odds of diabetes. Conversely, male gender, tobacco use, elevated BMI, poverty, being a migrant and advanced fibrosis were associated with increased odds of diabetes. The association between cannabis use and diabetes was maintained in the stratified analysis. In this large cross-sectional study of chronic HCV-infected patients, cannabis use was associated with a lower risk of diabetes independently of clinical and socio-behavioural factors. Further studies are needed to elucidate a potential causal link and shed light on cannabis compounds and mechanisms involved in this relationship.

Long-term clinical benefits of Sofosbuvir-based direct antiviral regimens for patients with chronic hepatitis C in Central and West Africa.

BACKGROUND: In Sub-Saharan Africa, chronic hepatitis C (CHC) is a major public health issue. We estimated the long-term clinical benefits of treating CHC with sofosbuvir-based regimens in Cameroon, Côte d'Ivoire and Senegal using Markov model combining data from the literature with estimates of direct-acting antiviral (DAAs) effectiveness in West and Central Africa. METHODS: Disease progression was simulated with and without treatment in fictive cohorts of patients "diagnosed" with CHC in Cameroon (n = 3224), Côte d'Ivoire (n = 9748) and Senegal (n = 6358). Lifetime treatment benefits were assessed using (a) life-years saved (LYS); (b) life-years (LY) avoided in compensated cirrhosis (CC), decompensated cirrhosis (DC) and hepatocellular carcinoma; and (c) comparison of the proportions of patients at each disease stage with and without treatment. Probabilistic and determinist sensitivity analyses were performed to address uncertainty. RESULTS: Sofosbuvir-based treatment would save [mean, 95% confidence intervals] 3.3 (2.5; 5.7) LY per patient in Cameroon, 2.7 (2.1; 4.8) in Côte d'Ivoire and 3.6 (2.8; 6.3) in Senegal. With treatment, approximately 6% (1%) of the patients still alive in each of the study countries would be in the CC (DC) health state 11 (15) years after CHC diagnosis, vs 15% (5%) without treatment. Scenario analysis showed earlier diagnosis and treatment initiation would dramatically improve LYS and morbidity. CONCLUSION: Sofosbuvir-based treatment could significantly reduce CHC-related mortality and help control CHC-related liver disease progression in West and Central Africa. However, the goal of disease elimination necessitates a substantial decrease in DAAs prices, greater political commitment and increases in both national and external health expenditures.

Incidence and Burden of Herpes Zoster in Sweden: A Regional Population-Based Register Study.

INTRODUCTION: Herpes zoster (HZ) is a painful disease that mainly affects individuals whose immune system has been weakened because of increasing age (> 50 years) or certain diseases or treatments. We estimated the complete burden of HZ. METHODS: This population-based register study analysed healthcare data from the VEGA and Digitalis databases of Västra Götaland Region (VGR), Sweden. The VEGA database includes all patients in VGR, covering both hospital and primary care. The Digitalis records prescribed medications. The study population included patients aged ≥ 18 years with at least one registered primary or secondary HZ diagnosis (based on International Classification of Diseases [ICD] codes) between 2005 and 2021. Incidence rates (95% confidence intervals [CI]) were stratified by age, sex and diagnosis/analgesic prescription. RESULTS: Overall HZ incidence increased from 2.5 (95% CI 2.4-2.6) in 2005 to 4.2 (95% CI 4.1-4.3) in 2021. The increase in incidence was rapid from 2005 to 2013, followed by a plateauing trend. From 2014-2019, the lifetime risk of HZ, excluding recurrent cases, was 36.5% (95% CI 35.5-37.4%). Municipal differences ranged from 34.4% (95% CI 32.5-36.4%) to 43.6% (95% CI 39.9-47.4%). Recurrence rates of HZ were 8.7% and 9.1% with follow-up periods of 5.5 and 10.5 years, respectively. Reported postherpetic neuralgia (PHN) cases increased five-fold over the study period. In 2019, 19% of all HZ patients developed HZ-related neuropathic pain; 13.6% had signs of persistent pain (> 90 days; i.e. PHN). An increased occurrence of cerebral and cardiovascular disease was observed in HZ patients. Among high-risk groups the occurrence of HZ peaked among those with inflammatory and autoimmune diseases. CONCLUSION: HZ and PHN risk in Sweden is comparable to that in other European countries prior to implementing HZ national vaccination programs. Municipal differences suggest that the lifetime risk of HZ in Sweden is at least 36.5%. CLINICAL TRIAL REGISTRATION: NCT Number ( www. CLINICALTRIALS: gov ).

What is the context?The varicella-zoster virus (VZV) can reactivate after primary infection and cause herpes zoster or shingles.Shingles is painful and mostly affects people aged > 50 years or those who have weakened immunity due to age, illness or medical treatments.The National Immunization Program (NIP) in Sweden does not currently include vaccination against shingles.We evaluated how often individuals from Västra Götaland Region, Sweden, experienced shingles and its complications.What is new?Overall, the number of shingles and PHN cases increased significantly from 2005 to 2021.We found that 14% of patients with shingles had pain persisting for > 3 months after a shingles episode.Most people developing shingles (about 70%) are healthy individuals without comorbidities, although those with underlying health issues have more risk of getting shingles.Over a follow-up period of 5.5 years, 8.7% of patients with shingles had more than one shingles episode.What is the impact?The occurrence of shingles and postherpetic neuralgia in Sweden is higher than what was reported previously and is comparable to other European countries before the implementation of shingles vaccination programmes.

Hepatitis B in Senegal: A Successful Infant Vaccination Program but Urgent Need to Scale Up Screening and Treatment (ANRS 12356 AmBASS survey).

Senegal introduced the infant hepatitis B virus (HBV) vaccination in 2004 and recently committed to eliminating hepatitis B by 2030. Updated epidemiological data are needed to provide information on the progress being made and to develop new interventions. We estimated the prevalence of hepatitis B surface antigen (HBsAg) in children and adults living in rural Senegal and assessed hepatitis B treatment eligibility. A cross-sectional population-based serosurvey of HBsAg was conducted in 2018-2019 in a large sample (n = 3,118) of residents living in the Niakhar area (Fatick region, Senegal). Individuals positive for HBsAg subsequently underwent clinical and biological assessments. Data were weighted for age and sex and calibrated to be representative of the area's population. Among the 3,118 participants, 206 were HBsAg positive (prevalence, 6.9%; 95% confidence interval [CI], 5.6-8.1). Prevalence varied markedly according to age group in individuals aged 0-4, 5-14, 15-34, and ≥35 years as follows: 0.0% (95% CI, 0.00-0.01); 1.5% (95% CI, 0.0-2.3); 12.4% (95% CI, 9.1-15.6); and 8.8% (95% CI, 6.1-11.5), respectively. Of those subsequently assessed, 50.9% (95% CI, 41.8-60.0) had active HBV infection; 4 (2.9%; 95% CI, 0.9-9.4) were eligible for hepatitis B treatment. Conclusion: In this first population-based serosurvey targeting children and adults in rural Senegal, HBsAg prevalence was very low in the former, meeting the World Health Organization's (WHO) < 1% HBsAg 2020 target; however, it was high in young adults (15-34 years old) born before the HBV vaccine was introduced in 2004. To reach national and WHO hepatitis elimination goals, general population testing (particularly for adolescents and young adults), care, and treatment scale-up need to be implemented.

Cost-Utility Analysis of a Dolutegravir-Based Versus Low-Dose Efavirenz-Based Regimen for the Initial Treatment of HIV-Infected Patients in Cameroon (NAMSAL ANRS 12313 Trial).

OBJECTIVES: Evidence comparing the economic and patient values of the World Health Organization's preferred (dolutegravir 50 mg [DTG]-based) and alternative (low-dose [400 mg] efavirenz [EFV400]-based) first-line antiretroviral regimens is limited. We compared patient-reported outcomes (PROs), costs, and the cost-utility of DTG- versus EFV400-based regimens in treatment-naive HIV-1 adults in the randomised NAMSAL ANRS 12313 trial in Yaoundé, Cameroon. METHODS: We used clinical data, PROs, and health resource use data collected in the trial's first 96 weeks (2016-2019). Quality-adjusted life-years (QALYs) were computed using utility scores obtained from the 12-item Short Form (SF-12) generic health scale. Other PROs included perceived symptoms, depression, anxiety, and stress. In the 96-week base-case analysis, we estimated the unadjusted and multivariate-adjusted (1) mean costs (in US$, 2016 values) and QALYs/patient, (2) incremental costs and QALYs/patient, and (3) net health benefit (NHB). Outcomes were extrapolated over 5 and 10 years. Uncertainty was assessed using the cost-effectiveness acceptability curve and scenario and cost-effective price threshold analyses. RESULTS: In the base-case analysis, the NHB (95% confidence interval) for the DTG-based regimen relative to the EFV400-based regimen was 0.056 (- 0.037 to 0.153), corresponding to an 88% probability of DTG being cost-effective. A 10% decrease in this regimen's price (from $5.2 to $4.7/month) would increase its cost-effectiveness probability to 95%. When extrapolating outcomes over 5 and 10 years, the DTG-based regimen had a 100% probability of being cost-effective for a large range of cost-effectiveness thresholds. CONCLUSIONS: At 2020 antiretroviral drug prices, a DTG-based first-line regimen should be preferred over an EFV400-based regimen in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02777229.

The Costs of Introducing the Hepatitis B Birth Dose Vaccine into the National Immunization Programme in Senegal (NéoVac Study).

Some African countries are still reluctant to introduce the hepatitis B vaccine birth dose (HepB-BD) into their expanded program of immunization (EPI), partly because of logistical, economic, and cost information constraints. To assist decision-makers in these countries, we assessed the economic and financial costs of HepB-BD introduction in Senegal in 2016. We performed a micro-costing study in a representative sample of Senegal's EPI sites at all levels in 2018. Information on EPI and HepB-BD activity-related inputs and costs was collected using standardized questionnaires and semi-structured interviews. Using inverse probability weighting, we computed weighted average costs associated with HepB-BD introduction for each EPI level, country-level aggregated costs and estimated costs per newborn. Economic and financial costs from a government perspective were estimated in US dollars for 2015, 2016 and 2017. Total economic costs were USD 143,364 in 2015, USD 759,406 in 2016 and USD 867,311 in 2017, while financial costs were USD 127,745, USD 82,519 and USD 29,853, respectively. When annualizing pre-introduction and initial training costs, the economic (financial) cost per vaccinated newborn was USD 2.10 (USD 0.30) in 2016 and USD 1.90 (USD 0.20) in 2017. Our estimates provide valuable information to implement HepB-BD in Sub-Saharan African countries that have not yet integrated this vaccine.

Cannabis use and reduced risk of elevated fatty liver index in HIV-HCV co-infected patients: a longitudinal analysis (ANRS CO13 HEPAVIH).

Background: Cannabis use and elevated fatty liver index (FLI≥ 60) (a biomarker of hepatic steatosis in the general population) have been identified as predictors of HCV-related and overall mortality, respectively, in HIV-HCV co-infected patients. However, the relationship between cannabis use and the risk of elevated FLI has never been explored.Methods: Using five-year follow-up data from 997 HIV-HCV co-infected patients (ANRS CO13 HEPAVIH cohort), we analyzed the relationship between cannabis use and FLI using mixed-effects multivariable logistic (outcome: elevated FLI yes/no) and linear (outcome: continuous FLI) regression models.Results: At the last follow-up visit, 27.4% of patients reported regular or daily cannabis use and 27.8% had elevated FLI. After multivariable adjustment, regular or daily cannabis use was associated with a 55% lower risk of elevated FLI (adjusted odds ratio [95% confidence interval]: 0.45 [0.22; 0.94]; p = 0.033) and lower FLI values (adjusted model coefficient: -4.24 [-6.57; -1.91], p < 0.0001).Conclusions: Cannabis use is associated with a reduced risk of elevated fatty liver index in HIV-HCV co-infected patients. Further research is needed to confirm whether and how cannabinoids may inhibit the development of hepatic steatosis or other metabolic disorders in high-risk populations.

Population attributable fractions of mortality in people living with HIV: roles of delayed antiretroviral therapy, hepatitis coinfections and social factors.

OBJECTIVES: Despite free access to antiretroviral therapy (ART) from 1996 onward, and treatment for all people living with HIV (PLWHIV) from 2013, mortality in Brazil has not homogeneously decreased. We investigated to what extent delayed ART, hepatitis coinfections and sociodemographic factors predict all-cause mortality in Brazilian PLWHIV. DESIGN: We included PLWHIV at least 18 years, with complete CD4 cell count data, followed up between 2007 and 2015 in Brazil. METHODS: After multiple imputation, an extended Cox model helped estimate the effects of fixed and time-varying covariates on mortality. RESULTS: The study population (n = 411 028) were mainly male (61%), white (55%), 40 years or less (61%), heterosexually HIV infected (71%), living in the Southeast region (48%) and had basic education (79%). Hepatitis C virus and hepatitis B virus coinfection prevalences were 2.5 and 1.4%, respectively. During a 4-year median follow-up, 61 630 deaths occurred and the mortality rate was 3.45 (95% confidence interval: 3.42-3.47) per 100 person-years. Older age, male sex, non-white ethnicity, illiteracy/basic education and living outside the Southeast and Central-West regions were independently associated with increased mortality. The main modifiable predictors of mortality were delayed ART (i.e. CD4 cell count <200 cells/µl at ART initiation) (adjusted population attributable fraction: 14.20% [95% confidence interval: 13.81-14.59]), being ART-untreated (14.06% [13.54-14.59]) and ART-treated with unrecorded CD4 at ART initiation (5.74% [5.26-6.21]). Hepatitis C virus and hepatitis B virus coinfections accounted for 2.44 [2.26-2.62] and 0.42% [0.31-0.53] of mortality, respectively. CONCLUSION: The current study demonstrates that besides early ART and coinfection control, actions targeting males, non-whites and illiterate people and those with basic education are important to reduce avoidable deaths among Brazilian PLWHIV.

Cost-Effectiveness Analysis of Lopinavir/Ritonavir Monotherapy Versus Standard Combination Antiretroviral Therapy in HIV-1 Infected Patients with Viral Suppression in France (ANRS 140 DREAM).

BACKGROUND: Protease inhibitor monotherapy is a simplified treatment strategy for virally suppressed HIV-positive patients that has the potential for cost savings, as fewer drugs are used than with combination therapy. However, evidence for its economic value is limited. OBJECTIVES: We assessed the cost-effectiveness of lopinavir/ritonavir monotherapy followed by treatment intensification in case of viral load rebound versus combination antiretroviral therapy (cART) with efavirenz/emtricitabine/tenofovir in HIV-1 infected patients with viral suppression in the ANRS 140 DREAM trial. METHODS: DREAM was conducted in 36 French Hospitals between 2009 and 2013. For each treatment strategy, we estimated the unadjusted and multivariate-adjusted mean costs (in €, year 2010 values) and quality-adjusted life-years (QALYs) per patient, as well as incremental costs and QALYs per patient. We then assessed uncertainty using the cost-effectiveness acceptability curve, scenario analyses and cost-effectiveness price-threshold (CEPT) analysis. RESULTS: In the base-case analysis considering 2009-2013 antiretroviral drug (ARV) prices, adjusted incremental costs and QALYs were - €3296 (95% confidence interval [CI] - 5202 to - 1391) and 0.006 (95% CI - 0.021 to 0.033), respectively, over 2 years, suggesting that monotherapy was cost-effective with a probability of 100% at various cost-effectiveness thresholds. In scenario analyses considering 2018 ARV prices, monotherapy remained cost-effective but with a lower probability (94% vs. 100% in the base-case analysis). The current price of cART would have to decrease by 34% to be cost-effective with a probability of 95%. CONCLUSION: Monotherapy appears to be cost-effective compared with cART for virologically suppressed HIV-positive patients in France. CEPT analysis is a useful tool to identify the preferred strategy to adopt given that ARV prices change rapidly. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00946595.