Abstract

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) are hyperendemic in sub-Saharan Africa. The HBV genotypes prevailing in HIV-infected Africans are unknown. Our aim was to determine the HBV genotypes in HIV-infected participants and to identify clinically significant HBV mutations. From 71 HBV DNA+ve HIV-infected participants, 49 basic core promoter/precore (BCP/PC) and 29 complete S regions were successfully sequenced. Following phylogenetic analysis of 29 specimens in the complete S region, 28 belonged to subgenotype A1 and one to D3. Mutations affecting HBeAg expression at the transcriptional (1762T1764A), translational (Kozak 1809–1812, initiation 1814–1816, G1896A with C1858T), or post translational levels (G1862T), were responsible for the high HBeAg-negativity observed. The G1862T mutation occurred only in subgenotype A1 isolates, which were found in one third (7/21) of HBsAg−ve participants, but in none of the 18 HBsAg+ve participants (p<0.05). Pre-S deletion mutants were detected in four HBsAg+ve and one HBsAg−ve participant/s. The following mutations occurred significantly more frequently in HBV isolated in this study than in strains of the same cluster of the phylogenetic tree: ps1F25L, ps1V88L/A; ps2Q10R, ps2 R48K/T, ps2A53V and sQ129R/H, sQ164A/V/G/D, sV168A and sS174N (p<0.05). ps1I48V/T occurred more frequently in females than males (p<0.05). Isolates with sV168A occurred more frequently in participants with viral loads >200 IU per ml (p<0.05) and only sS174N occurred more frequently in HBsAg−ve than in HBsAg+ve individuals (p<0.05). Prior to initiation of ART, ten percent, 3 of 29 isolates sequenced, had drug resistance mutations rtV173L, rtL180M+rtM204V and rtV214A, respectively. This study has provided important information on the molecular characteristics of HBV in HIV-infected southern Africans prior to ART initiation, which has important clinical relevance in the management of HBV/HIV co-infection in our unique setting.

Highlights

  • Hepatitis B virus (HBV), with a genome of,3,200 base pairs, is the smallest DNA virus infecting humans, yet it is one of the most important human pathogens, causing major health problems globally

  • The relatively longer amplicon of the S region compared to the basic core promoter/precore (BCP/PC) region, meant that fewer samples could be sequenced in that region successfully

  • Compared to areas of low endemicity, where human immunodeficiency virus (HIV) and HBV are most likely transmitted at the same time during sexual maturity, in southern Africa, where both viruses are endemic, HBV infection occurs before the age of 5 years and these children become chronic carriers of HBV in adulthood [8]

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Summary

Introduction

Hepatitis B virus (HBV), with a genome of ,3,200 base pairs, is the smallest DNA virus infecting humans, yet it is one of the most important human pathogens, causing major health problems globally. The two viruses share a common mode of transmission and can co-exist in the same host [4], and HBV and HIV co-infections are frequent in sub-Saharan Africa [5]. Because HBV infection precedes HIV infection in sub-Saharan Africa [5], the HBV exposure rate does not differ from that found in HBV monoinfected [6,7,8,9]. Even though direct comparison between studies is difficult because of differences in study design and geographical regions, a range of 28% to 99.8% exposure to HBV and 0.4% to 23% HBsAg prevalence have been found in HIV-infected South African cohorts [10,11,12,13,14,15,16,17,18,19,20]. Comparisons between HBV mono-infected and HBV/HIV co-infected individuals are further confounded by the fact that since the introduction of universal HBV vaccination in April 1995, no comprehensive studies have been carried out in South Africa to determine either the exposure or prevalence rates of HBV infection

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