A 12-week course of sofosbuvir/ledipasvir proved highly effective in a sub-Saharan African setting, results of a study carried out in Rwanda show. The findings were presented on Friday at the 2018 International Liver Congress in Paris.
But, the study also found that people who were classified as reactive to both genotypes 1 and 4 were much less likely to be cured by treatment, indicating the importance of field implementation studies for identifying the diversity of viral genotypes and treatment responses across genotypes as direct-acting antivirals become available in lower-income countries.
The prevalence of hepatitis C ranges from less than 1% in southern Africa to around 8% in central Africa. Prevalence in eastern Africa is approximately 3%, according to a synthesis of prevalence estimates published in 2016. Approximately 140,000 people are estimated to be living with hepatitis C in Rwanda.
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
Access to direct-acting antiviral treatment has been very limited owing to cost, lack of drug registration and approval, lack of experience in treating viral hepatitis and lack of testing, as well as resource-limited health systems.
Extensive experience in the delivery of antiretroviral treatment for HIV infection in sub-Saharan Africa shows that diagnosis, treatment and monitoring of a chronic viral infection are achievable with the investment of resources and training of healthcare workers.
The Simplifying Hepatitis C Antiviral Therapy in Rwanda for Elsewhere in the Developing World (SHARED) study was a proof-of-concept pilot of direct-acting antiviral treatment. The study was sponsored by Partners in Health, a Boston-based organisation that has worked extensively to develop models of care suitable for management of conditions including cancer, tuberculosis and HIV in resource-limited settings such as Malawi and Rwanda.
Three hundred people with genotype 1 or 4 hepatitis C infection were enrolled in this prospective study of sofosbuvir/ledipasvir treatment. The study excluded people with decompensated cirrhosis, hepatitis B virus co-infection or hepatocellular carcinoma. The study also excluded people with HIV/hepatitis C virus (HCV) co-infection if their HIV infection was not fully suppressed on antiretroviral therapy.
Participants had a median age of 64 years, 62% were women, 10% had co-infection with HIV and 83% had a genotype 4 infection. The study population was predominantly poor (82% had a median monthly income < $120 a month), unemployed (64%) and had limited formal education (62% had primary education only).
Twelve weeks after the completion of treatment 87% of participants had achieved a sustained virologic response (SVR12) but a sub-group of participants who were reactive to both genotypes 1 and 4 on a genotyping test had a lower cure rate (60%). Viral sequencing showed that 13% of people (n = 39) had the '4r' variant of genotype 4 and virologic response was markedly lower in those with '4r' (54%) than in those with other sub-genotypes (87-100%). Seventy-eight per cent of those reactive to genotypes 1 and 4 had the '4r' sub-genotype. Seventeen participants with the '4r' sub-genotype experienced viral relapse after completing treatment. The '4r' genotype has been identified in Rwanda, the Democratic Republic of Congo and southern Ethiopia.
No participant discontinued treatment due to an adverse event but grade 3 or 4 adverse events were experienced by 16-18% of study participants. Participants often had little previous health care and many chronic problems were diagnosed for the first time during the study, such as hypertension (32%).
The researchers concluded HCV treatment can be delivered by non-specialist teams with limited laboratory monitoring in resource-limited settings but expressed concern regarding the potential for unexpected lack of response.