Edina Amponsah-Dacosta1, J Nare Rakgole1, Maemu P Gededzha1, Azwidowi Lukhwareni2, Jason T Blackard3, Selokela G Selabe1, M Jeffrey Mphahlele4. 1. HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa. 2. HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa; National Health Laboratory Service, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa. 3. Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 4. HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa; South African Medical Research Council, Soutpansberg Road, Pretoria, South Africa. Electronic address: Jeffrey.Mphahlele@mrc.ac.za.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. MATERIALS AND METHODS: This retrospective study investigated the molecular evolution of chronic HBV in HIV co-infectedpatients on lamivudine (3TC)-based HAART over a 5year period. Four HIV co-infectedpatients, 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. RESULTS: 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. CONCLUSION: Despite persistent HBV infection in the HIV co-infectedpatients 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.
Authors: Mohube B Maepa; Abdullah Ely; Anna Kramvis; Kristie Bloom; Kubendran Naidoo; Omphile E Simani; Tongai G Maponga; Patrick Arbuthnot Journal: Viruses Date: 2022-08-31 Impact factor: 5.818