Monitoring the Impact of HIV-1 Coexistence on Molecular Evolution of Hepatitis B Virus

CASSINO L; MBAYED V; TORRES C; CAMPOS R; LAUFER N; QUARLERI J

Boston, MA, USA

Conferencia; 18th Conference on retrovirus and Opportunistic Infections; 2011

Background: HIV infection has a significant impact on the natural history of chronic hepatitis B (HBV) infection. When in monoinfection, both viruses exhibit rapid evolutionary dynamics, typical of viruses dependent on reverse transcriptase-mediated replication. Our aim was to analyze the impact of HIV on the evolutionary rate of HBV at inter and intra-host levels in a 3-year longitudinal study. Methods: Two samples from 17 chronically infected HBV patients (9 HIV-coinfected) were collected at 1 and 36 months during a period of 3 years. Patients’ CD4 T cell counts, HBV genotype, HIV and HBV viral load, lamivudine therapy and its related mutations and antiretroviral regimen were documented. HBV DNA was amplified from two preC/C and S genomic regions, which were cloned and sequenced with further evaluation of positive/negative selection of T cell epítopes. Phylogenetic and evolutionary rates were estimated by ML and Bayesian method, respectively. The HBV quasispecies heterogeneity analysis involved complexity and diversity. Results: The CD4+ T cell counts were significantly higher in HBV monoinfected individuals than in HIV coinfected ones (p<0.05, T test). The HBV ancestral origin did not appear to be influenced by HIV coexistence. HBV evolutionary rate, based on S and preC/C sequences from HBV monoinfected individuals was almost two fold higher than those coinfected. The HBV quasispecies heterogeneity analysis revealed that diversity and complexity were higher among isolates from monoinfected versus coinfected individuals (p<0.05, T test). In the two HBV studied ORFs, no codons under positive selection were identified and only few codons under negative selection were identified in HBV monoinfected patients but in any case T cell epítopes were not affected. Discussion: The presence of HIV impacts the molecular evolution of HBV. The complex pattern of overlapping reading frames in the HBV genome constrains viral evolution. The slightly higher rate and heterogenenicity of quasispecies observed in monoinfected individuals suggests an adaptation of viral variants to a disadvantageous environment, such as potentially higher immune pressure or antiviral therapy. As expected, T cell epitopes were conserved at amino acid level supporting functionally constraint and limiting higher evolutionary rates. These data suggest that the discrepancies observed in the HBV evolutionary rates when there is HIV coinfection may reflect different population dynamics.