Development of hepatotoxicity in individuals harbouring different HIV subtypes and drug-resistant variants in Cameroon

Objective: The aim of this study was to determine the effect of HIV-1 genetic variants and drug resistance-associated mutations (DRM) on the development of hepatotoxicity. Design and participants: This was a longitudinal study of 81 newly diagnosed HIV-infected individuals in five HIV Treatment clinics in the Northwest Region (NWR) of Cameroon from February 2016 to November 2016. Methodology: Eighty-one antiretroviral drug-naive patients were recruited into the study and followed-up for 6 months. Blood samples were collected prior to ART initiation and 180 days (D180) later. Serum levels of aminotransferases were analyzed by enzymatic  methods. The HIV-1 protease and reverse transcriptase sequences were obtained using an in-house protocol and DRMs were identifiedusing the Stanford HIVDR interpretation program, and HIV-1 subtypes by phylogeny. Results: The mean age of the study participants was 36.5 years. Of these, 37(45.7%) patients showed hepatotoxicity at D180. There were four pure subtypes and five recombinant types with CRF02_AG (74.1%) being the predominant genetic variants. The prevalence of hepatotoxicity was highest among individuals infected with HIV-1 CRF02_AG (70.3%). The prevalence of DRM was 11.1% (9/81).  Hepatotoxicity was significantly (p =0.04) higher 77.8% (7/9) among patients with resistant virus. Conclusion: Data from this study reveals a high level of hepatotoxicity among patients with DRM probably as a result of persistent viral replication. These findings highlight the need to conduct routinely DRM surveillance among patients with hepatotoxicity in order to improve patient management and care.