Evidence of susceptibility to lamivudine-based HAART and genetic stability of hepatitis B virus (HBV) in HIV co-infected patients: A South African longitudinal HBV whole genome study

• Published in: Infection, genetics and evolution genetics and evolution, 2016-09, Vol.43, p.232-238
• Main Authors: Amponsah-Dacosta, Edina, Rakgole, J. Nare, Gededzha, Maemu P., Lukhwareni, Azwidowi, Blackard, Jason T., Selabe, Selokela G., Mphahlele, M. Jeffrey
• Format: Article
• Language: English
• Subjects: 3TC-based HAART; Adult; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Coinfection; DNA, Viral - genetics; Evolution, Molecular; Female; Genetic variability; Genome, Viral; Genotype; HBV; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B virus - growth & development; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - virology; HIV; HIV - drug effects; HIV - genetics; HIV - growth & development; HIV Infections - drug therapy; HIV Infections - virology; Humans; Lamivudine - therapeutic use; Male; Microbial Sensitivity Tests; Middle Aged; Molecular evolution; Retrospective Studies; South Africa; Viral Load; Whole genome
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2016.05.035

Reports on the concomitant impact of HIV co-infection and long term highly active anti-retroviral therapy (HAART) on the genetic stability and molecular evolution of HBV are limited in sub-Saharan Africa. This retrospective study investigated the molecular evolution of chronic HBV in HIV co-infected patients on lamivudine (3TC)-based HAART over a 5year period. Four HIV co-infected patients, consecutively recruited and followed-up, were screened for hepatitis B serological markers, and their viral loads determined. The HBV genome was amplified from longitudinal samples and characterized by Bayesian inference, mutational analysis, and identification of immune selection pressure. All patients exhibited persistent chronic HBV infection at baseline, as well as over the course of follow-up despite exposure to 3TC-based HAART. The polymerase gene in all isolates was relatively variable prior to HAART initiation at baseline and during the course of follow-up, although primary drug resistance mutations were not detected. All but one patient were infected with HBV subgenotype A1. The divergence rates between baseline and the last follow-up sequences ranged from 0 to 2.0×10−3 substitutions per site per year (s/s/y). Positive selection pressure was evident within the surface and core genes. Despite persistent HBV infection in the HIV co-infected patients exposed to long term 3TC-based HAART, the molecular evolution of HBV over a 5year period was unremarkable. In addition, HBV exhibited minimal genetic variability overtime. •HIV positive patients experienced persistent HBV chronic infection despite exposure to long term 3TC-based HAART.•Notably, primary drug resistant variants were not isolated prior to or during 3TC-based HAART.•Overall, divergence rates of HBV isolates were indicative of minimal genetic variability overtime.