Community-based, individualized, hepatitis C therapy in Nepal

Purpose: With direct acting antiviral therapy (DAA) expansion to resource-limited settings there is an urgency to validate best practices for population-based screening and treatment of hepatitis C (HCV). The Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbH (German Development Cooperation) implemented a community-based screening and treatment model for mono-infected and HIV/HCV co-infected persons in Nepal where over 150,000 individuals are living with HCV genotype 3 (GT3: 60%) and genotype 1 (GT1: 40%) (Kinkel, H). Methods: We “pivoted” HCV screening and treatment within 3 existing opioid substitution treatment (OST) sites screening 600 patients with HCV viral load and GT, AST/ Platelet Ratio Index (APRI) and fibroscan; enrolling 150 HCV mono-infected and 150 HIV-HCV co-infected for individualized treatment in an ongoing study. Patients with GT3 disease with optimal predictors (baseline HCV viral load <3,000,000 IU/ ml, HIV-negative, no cirrhosis, age <50, body mass index < 30 kg/m2, favorable IL28B SNP) received 12-weeks sofosbuvir/ peg-IFN-RBV (SIR) vs S/daclatasvir (SD) +/- R (cirrhotics). GT1-regimens included: S/ledipasvir (SL) or SD +/- R (cirrhotics). Results: We demonstrated optimal 4-week complete rapid virologic response (RVRc) (94%) without significant toxicity among the first 105 patients treated (n=69 HIV+; 50% with tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens). Treatment regimens were: 50% SD and 35% SL (with R for 17 patients with compensated cirrhosis), 15% SIR. An APRI cut-off of 2 (compared to fibroscan 10) had 51% sensitivity, 95% specificity (89% negative predictive value) for advanced fibrosis. Conclusions: Both optimal outcomes and drug tolerability demonstrated the effectiveness of community, OST-based HCV screening and treatment in a resource-limited setting with simple individualized DAA-based therapy. Excellent early outcomes across GT 1 and 3 in this “real-life” setting encompassing HIV-infected and injecting drug users supports simple HCV diagnostic/treatment models implemented through OST sites. These results will be valuable for extending population- based HCV treatment to resource-limited settings. Reference: Kinkel H et al. Prevalence of Hepatitis B and C infection and assessment of HCV-genotype among people who inject drugs in three regions of Nepal (PloS One, 2015).