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

Abstract

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.

Keywords: Cameroon; Chronic hepatitis C; Cost-effectiveness analysis; Cost-utility analysis; Côte d’Ivoire; Direct-acting antivirals; Senegal; Sofosbuvir.

Fig. 1

Simplified diagram of the Markov model. The oval boxes represent the different health states in the model, including two absorbing health states (CHC-related and CHC-unrelated deaths; the latter is not represented in the diagram for simplification purposes) and the following transient health states: fibrosis stages F0 to F3 (measured using the METAVIR scoring system), CC, DC and HCC. At model entry (CHC infection), all patients had a detectable viral load and were at the F0, F1, F2, F3 or CC stages. Arrows on full lines denote the transitions between health states according to treatment decision (i.e., whether patients received treatment or not) and treatment success (i.e., whether patients achieved SVR after treatment or not). The disease progression stops in all cured patients (i.e., who achieved SVR) except in patients in the CC health state at the end of the treatment cycle. Patients in the F3, CC, DC and HCC health states had a risk of CHC-related death. In addition, patients had a risk of CHC-unrelated death in all health states, corresponding to the “natural mortality” rate, which depends on age, gender and country. Arrows on dashed lines show reinfection in patients who achieved SVR. Abbreviation: CC, Compensated Cirrhosis; CHC, Chronic Hepatitis C; CHC RD, Chronic hepatitis C-related death; DC, Decompensated Cirrhosis; F0-F3, METAVIR fibrosis stages F0 to F3; HCC, Hepatocellular Carcinoma; SVR, Sustainable Virologic Response

Fig. 2

Cost-effectiveness acceptability curves for sofosbuvir/velpatasvir versus the status-quo (Scenario 1: originator prices) (a) and for sofosbuvir/daclatasvir versus the status-quo (Scenario 2: generic prices) (b) in Cameroon, Côte d’Ivoire and Senegal. The colored vertical lines (green, red and blue) indicate the cost-effectiveness thresholds of 0.5 times the GDP/capita in 2017 for each of the three study countries (i.e., US$683.5 in Senegal, US$711 in Cameroon, US$778.5 in Côte d’Ivoire, respectively). The cost-effectiveness acceptability curves show the probability that the preferred regimen in each scenario (i.e., sofosbuvir/velpatasvir in scenario 1 (a) and sofosbuvir/daclatasvir in scenario 2 (b)) is cost-effective compared with the status quo at various cost-effectiveness thresholds ranging from US$0 to US$1500/QALY. The green, red and blue curves correspond, respectively, to Senegal, Cameroon and Côte d’Ivoire. Abbreviations: GDP: Gross Domestic Product; ICER: Incremental cost-effectiveness ratio; QALYs: Quality adjusted Life-years