HBV mutations in untreated HIV-HBV co-infection using genomic length sequencing

Abstract

HIV infection has a significant impact on the natural progression of hepatitis B virus (HBV) related liver disease. In HIV-HBV co-infected patients, little is known about mutations in the HBV genome, which can influence severity of liver disease. The aim of this study was to characterize and to determine the frequency of known clinically-significant mutations in the HBV genomes from HIV-HBV co-infected patients and from HBV mono-infected patients. To accomplish this, genomic length HBV sequencing was performed in highly-active anti-retroviral therapy (HAART) –naïve HIV-HBV co-infected patients (n= 74) and in anti-HBV therapy-naïve HBV mono-infected patients (n=55). The frequency of HBV mutations differed between the co-infected and mono-infected patients when comparing patients with the same genotype. BCP mutations A1762T and G1764A were significantly more frequent in HBV genotype C mono-infection and the −1G frameshift was significantly more frequent in co- infection and was only observed in HBV genotype A co-infection. PreS2 deletions were observed more frequently in the setting of co-infection. Further work is needed to determine if these mutational patterns influence the differences in liver disease progression in HIV-HBV co-infected and HBV mono-infected patients.

Comparative analysis of hepatitis B virus genotype a molecular evolution in patients infected with HBV and in patients co‐infected with HBV and HIV

“…Even so, the frequency of mutations under positive selection was lower among patients co-infected with HBV and HIV. This is consistent with the weaker HBVspecific T-cell response observed in HIV-HBV coinfection [Audsley et al, 2010].…”

“…Two different factors, such as the high HBV replication capacity and the lack of proofreading activity by the HBV polymerase, contribute to the development of quasispecies complexity and diversity during infection. The HBV quasispecies composition appears to be different when HIV is present, as previously reported [Cassino et al, 2009;Audsley et al, 2010]. The present study demonstrates that the intra-host analyses of HBV isolates revealed high complexity and diversity among patients infected with HBV exhibiting higher numbers of viral variants and genetic distance.…”

“…The impact of the dynamic changes on the HBV quasispecies heterogeneity from different genomic regions is unknown in HBV-HIV co-infected patients. To date, sequence analyses of the HBV genome in individuals co-infected with HBV-HIV have been limited to direct sequencing of complete genomes [Audsley et al, 2010], and partial genomic regions [Matthews et al, 2006] at a single time-point.…”

Genotyping and virological characteristics of hepatitis B virus in HIV-infected individuals in Sudan

“…43 The presence of deletion mutants in HBV from HBV/HIV co-infected individuals has been described in genotype A, both subgenotype A1 44 and subgenotype A2. 45 PreS2F22L was found in four isolates from HBsAg-positive HBV/HIV co-infected individuals and was found to be significantly associated with G1896A. PreS2F22L has been significantly associated with cirrhosis 46 and has been shown to be a risk factor for the development of HCC in Chinese patients infected with genotype C 47 and in Indian patients infected with genotype D. 46,48 HIV infection has been intimated to increase the hepatocarcinogenic potential of HBV.…”

Molecular Evolution of Hepatitis Viruses

“…This mutation results in premature termination of the deduced HBV precore and core genes and was associated with high HBV viral load. PreS2 deletions were observed more frequently in co-infection (Audsley et al, 2010). …”