Ledipasvir-sofosbuvir treatment for chronic hepatitis C virus (HCV) infection may be efficacious, safe, and tolerable for HCV genotype 1 and 4 in adults in Rwanda, according to a study published in Lancet Gastroenterology Hepatology.
Of the 71 million individuals infected with HCV globally, approximately 10 million live in sub-Saharan Africa, which contributes to high mortality in this area as a result of cirrhosis and hepatocellular carcinoma. However, access to HCV treatment in this region remains limited despite the development of generic direct-acting antivirals (DAA). Ambitious goals have been established in Rwanda to facilitate HCV elimination with steps toward this goal including establishment of strong national governance and planning systems, development of diagnostic capacity, regulatory approval and introduction of DAA, and training of key health professionals.
Although HCV genotype 4 is the predominant genotype in this region, the epidemiology, diversity, and resistance profile of genotype 4 is largely unknown in this area. Further, few prospective studies on DAA efficacy and safety from this region exist. Therefore, this study aimed to establish the safety and efficacy of ledipasvir‑sofosbuvir for chronic HCV genotype 1 or 4 infection in adults in Rwanda (ClinicalTrials.gov identifier: NCT02964091).
Between 2017 and 2018, 300 participants (aged ³18 years) with HCV genotype 1 or 4 infection and a plasma HCV RNA concentration of >1000 IU/mL were enrolled from 4 HCV treatment centers in Rwanda. All participants were given a single combination tablet composed of 90 mg ledipasvir and 400 mg sofosbuvir once daily for 12 weeks. HCV genotype was established using an Abbott platform and HCV subtype was established with polymerase chain reaction amplification. The primary efficacy outcome was the proportion of participants who had sustained virologic response, which was defined as no quantifiable HCV RNA in the plasma 12 weeks after the end of study treatment. The primary safety outcome was the proportion of participants with grade 3 or 4 adverse events.
Genotyping results showed that 83% of participants had genotype 4, 1% had genotype 1, and 16% had both genotype 1 and genotype 4. Viral sequencing showed that all participants had genotype 4 infection; 45% of participants had subtype 4k, 16% had subtype 4r, 14% had subtype 4q, and 8% had subtype 4v.
The results demonstrated a high rate of treatment adherence and that ledipasvir-sofosbuvir was safe, effective, and well tolerated. In addition, 87% of participants achieved sustained virologic response through week 12 of treatment. However, genotype subtype 4r was found by viral sequencing in a high proportion of study participants (16%) and was associated with substantially lowered sustained virologic response at 12 weeks posttreatment (56%) than other subtypes (93%). The most common adverse events were hypertension (32%), headache (26%), dizziness (20%), and fatigue (19%); however, none of the adverse events was thought to be caused by the study drug. Further, there were no drug-related treatment discontinuations.
Overall, the study authors concluded that, “Genotype 4r is uniquely expressed in this region and associated with high rates of treatment failure, suggesting a need for rigorous test-of-cure in clinical practice and consideration of the use of newer pangenotypic [DAA] regimens in this region.”
Disclosure: This study was funded by Gilead Science.
Gupta N, Mbituyumuremyi A, Kabahizi J, et al. Treatment of chronic hepatitis C virus infection in Rwanda with ledipasvir-sofosbuvir (SHARED): a single-arm trial [published online December 11, 2018]. Lancet Gastroenterol Hepatol. doi: 10.1016/S2468-1253(18)30382-0