Late presentation for HCV care: Time to target people with diabetes and/or hazardous alcohol use (ANRS CO22 HEPATHER cohort).

BACKGROUND AND AIMS: Late presentation for care of hepatitis C virus (HCV) infection - defined as having severe liver fibrosis when first consulting a specialist for HCV care - increases morbidity and mortality. Identifying the socio-behavioural correlates of late presentation is essential to improve HCV strategies to optimize HCV cascade of care. We investigated clinical and socio-behavioural correlates of late presentation for care in HCV mono-infected individuals. METHODS: This study included chronic HCV mono-infected patients participating in the French national cohort ANRS CO22 HEPATHER, starting in 2012. The correlates of late presentation were estimated using a Heckman probit selection model, which takes into account the possible selection bias because of missing data in the outcome. RESULTS: Among the 9174 study patients, 1236 had available data on liver fibrosis stage at first presentation for HCV care. Of these, 591 (47.8%) were late presenters. In a multivariable analysis adjusted for age, sex and HCV genotype, having diabetes (adjusted coefficient [95% confidence interval]: 0.55 [0.30; 0.80]), current hazardous alcohol use (0.36 [0.03; 0.69]) and current abstinence but past hazardous alcohol use (0.42 [0.19; 0.64]) (vs. current abstinence and no past hazardous use) were all independently associated with late presentation for HCV care. CONCLUSIONS: As late presentation severely affects HCV cascade of care, our findings bring important new evidence about the need to promptly identify and target people with diabetes and/or past or current hazardous alcohol use for HCV screening and treatment within the wider context of the WHO goal to eliminate HCV by 2030.

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.

Effectiveness of direct-acting antivirals for chronic hepatitis C treatment in migrant and non-migrant populations in France.

Despite universal health coverage in France, migrants face specific socioeconomic barriers that increase the likelihood of a suboptimal cascade of care for chronic hepatitis C virus (HCV) infection and impaired treatment effectiveness in this sub-population. We selected data collected from 2012 to 2018 from the ANRS CO22 HEPATHER prospective cohort study for chronic HCV participants with available data on treatment failure (defined as the presence of a detectable HCV-RNA load 12 weeks after their first DAA treatment ended). We performed multivariable Poisson regression models to test whether treatment failure rates differed significantly between HCV-infected migrants and non-migrants receiving DAA in France (cross-sectional analysis), while taking into account the former's world region of birth and other potential social vulnerability factors. Among the study population's 7,879 patients, 5,829 (74%) were non-migrants and 2,050 (26%) migrants. Median [interquartile range] age was 57 [51-65] years, 4433 (56%) were men and 369 (5%) of the entire study population had treatment failure. After multivariable adjustment, only migrants from Central Asia were at higher risk of treatment failure than non-migrants (aIRR = 2.83; 95% CI [1.72, 4.65]). Results from this large-scale study performed in France suggest a higher risk of DAA treatment failure in migrants from Central Asia than in non-migrants and confirm the overall low treatment failure rate in chronic HCV patients treated with DAA (whether migrants or not). Simplified models of care taking into account language and cultural barriers are needed to improve DAA effectiveness in migrants from Central Asia.

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.

Individual and healthcare supply-related barriers to treatment initiation in HIV-positive patients enrolled in the Cameroonian antiretroviral treatment access programme.

Increasing demand for antiretroviral treatment (ART) together with a reduction in international funding during the last decade may jeopardize access to ART. Using data from a cross-sectional survey conducted in 2014 in 19 HIV services in the Centre and Littoral regions in Cameroon, we investigated the role of healthcare supply-related factors in time to ART initiation in HIV-positive patients eligible for ART at HIV diagnosis. HIV service profiles were built using cluster analysis. Factors associated with time to ART initiation were identified using a multilevel Cox model. The study population included 847 HIV-positive patients (women 72%, median age: 39 years). Median (interquartile range) time to ART initiation was 1.6 (0.5-4.3) months. Four HIV service profiles were identified: (1) small services with a limited staff practising partial task-shifting (n = 4); (2) experienced and well-equipped services practising task-shifting and involving HIV community-based organizations (n = 5); (3) small services with limited resources and activities (n = 6); (4) small services providing a large range of activities using task-shifting and involving HIV community-based organizations (n = 4). The multivariable model showed that HIV-positive patients over 39 years old [hazard ratio: 1.26 (95% confidence interval) (1.09-1.45), P = 0.002], those with disease symptoms [1.21 (1.04-1.41), P = 0.015] and those with hepatitis B co-infection [2.31 (1.15-4.66), P = 0.019] were all more likely to initiate ART early. However, patients in the first profile were less likely to initiate ART early [0.80 (0.65-0.99), P = 0.049] than those in the second profile, as were patients in the third profile [association only significant at the 10% level; 0.86 (0.72-1.02), P = 0.090]. Our findings provide a better understanding of the role played by healthcare supply-related factors in ART initiation. In HIV services with limited capacity, task-shifting and support from community-based organizations may improve treatment access. Additional funding is required to relieve healthcare supply-related barriers and achieve the goal of universal ART access.