Hepatitis B and C Co-Infection among HIV-Infected Adults while on Antiretroviral Treatment: Long-Term Survival, CD4 Cell Count Recovery and Antiretroviral Toxicity in Cambodia

Background: Despite the high burden, there is a dearth of (long-term) outcome data of hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infected patients receiving antiretroviral treatment (ART) in a clinical setting in resource-constrained settings, particularly from Asia. Methods: We conducted a retrospective cohort study including all adults initiating standard ART (non-tenofovir-based) between 03/2003 and 09/2012. HBV infection was diagnosed by HBV surface antigen detection. HCV diagnosis relied on antibody detection. The independent effect of HBV and HCV on long-term (>= 5 years) ART response in terms of mortality (using Cox regression), severe livertoxicity (using logistic regression) and CD4 count increase (using mixed-effects modelling) was determined. Results: A total of 3089 adults were included (median age: 35 years (interquartile range 30-41); 46% male), of whom 341 (11.0%) were co-infected with HBV and 163 (5.3%) with HCV. Over a median ART follow-up time of 4.3 years, 240 individuals died. Mortality was 1.6 higher for HBV co-infection in adjusted analysis (P = 0.010). After the first year of ART, the independent mortality risk was 3-fold increased in HCV co-infection (P = 0.002). A total of 180 (5.8%) individuals discontinued efavirenz or nevirapine due to severe livertoxicity, with an independently increased risk for HBV (hazard ratio (HR) 2.3; P<0.001) and HCV (HR 2.8; P<0.001). CD4 recovery was lower in both HBV and HCV co-infection but only statistically significant for HBV (P<0.001). Discussion: HBV and HCV co-infection was associated with worse ART outcomes. The effect of early ART initiation and providing effective treatment for hepatitis co-infection should be explored.