Evaluation Of Genetic Diversity, Drug Resistance Mutational And Cytokine Patterns On Hepatotoxicity Markers Among Hiv Patients In Northwest Region, Cameroon

Highly active anti-retroviral therapy (HAART) has been known to cause hepatotoxicity despite its benefit to improve the morbidity and mortality associated with HIV infections. However, the impact of HAART on HIV subtypes, drug resistance mutations and cytokine profiles, is not yet fully elucidated especially in the Northwest Region (NWR) of Cameroon. Therefore, this study was carried out with aim of determining the effect of HIV-1 subtypes, drug resistance mutations, cytokine profiles and risk factors on hepatotoxicity markers among HIV-1 drug naïve adults in the NWR of Cameroon. This was a longitudinal study conducted from February to November 2016 and newly diagnosed HIV-1 drug-naive patients were recruited into the study. Stratified and simple random sampling techniques were used in selecting the five study sites. Blood samples were collected prior to HAART initiation Day (D) 0 and at D30 and D180. The participants were placed on either Tenofovir (TDF) + Lamivudine (3TC) + Efavirenz (EFV) or Zidovudine (AZT) + 3TC + Nevirapine (NVP) or AZT+3TC+EFV regimens. Serum levels of alanine aminotransferases (ALT), aspartate aminotransferases (AST) and alkaline phosphatase (ALP) were analyzed. Human Th1/Th2/Th17 cytokines were measured using a cytometric bead array assay. Genotypic and transmitted drug resistance (TDR) analyses were performed by sequencing HIV virus using an in-house protocol. Data were analyzed using SPSS vs. 23 and Graph pad prism 6. HIV-1 subtypes were determined phylogenetically using MEGA vs. 7 while TDR and resistance-associated mutations (RAMs) were identified using the Stanford HIVDR interpretation program. The level of significance was set at 5%. In all, 100 individuals participated in the study with a mean (age range) of 36.5 (18-61) years. Of this, 37(37%) and 49(49%) patients presented with hepatotoxicity while 15% and 28% of patients had severe hepatotoxicity at D30 and D180 respectively. Serum levels of ALT, AST and ALP increased significantly (p