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

LUCILA CASSINO; VIVIANA MBAYED; CAROLINA TORRES; RODOLFO CAMPOS; NATALIA LAUFER; JORGE QUARLERI

Boston, Estados Unidos

Conferencia; 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011); 2011

Background: both HIV and HBV exhibit rapid evolutionary dynamics, typical of viruses dependent on reverse transcriptase-mediated replication. The former has a significant impact on the natural history of chronic HVB infection but little is known on the reciprocal impact in the dynamics of molecular evolution. Aim: to analyze the impact of HIV-1 on the evolutionary rate of HBV at inter and intra-host levels in a prospective 3-year longitudinal study.Methods: serum samples from 17 chronically infected HBV patients (9 HIV-1 coinfected) were collected at baseline and 36 months after. Patients´ CD4 cell count, HBV genotype, HIV-1 and HBV viral load, lamivudine therapy, its related mutations and antiretroviral regimen were documented. HBV DNA was amplified, from preC/C and S genomic regions. Phylogenetic and evolutionary rates were estimated by ML and Bayesian method, respectively. The HBV quasispecies heterogeneity analysis involved its complexity and diversity. Statistical analysis was performed using student T test. Results: The CD4+ cell counts were higher in HBV monoinfected individuals vs. those coinfected (952.1 vs. 237-8, respectively; p>0.05). The HBV ancestral origin was not influenced by HIV-1 coexistence. Evolutionary rate, based on S and preC/C sequences from HBV monoinfected individuals, was 2 fold higher compared to those coinfected. The HBV quasispecies heterogeneity analysis revealed that diversity and complexity were higher among isolates from monoinfected individuals (p<0.05). In the two studied ORFs, no codons under positive selection were indentified. Few codons under negative selection were indentified in HBV monoinfected patients. In any case T cell epitopes were not affected.Discussion: HIV-1 impacts the molecular evolution of HBV. The complex pattern of overlapping reading framesin the HBV genome constrains viral evolution. The slightly higher rate and heterogenecity of quasispecies observed in monoinfected individuals suggest an adaptation of viral variants to a disadvantageous environment, such as potentially higher immune pressure or antiviral therapy. T cell epitopes were conserved at amino acid level supporting functionally constraint and limiting higher evolutionary rates when there is HIV-1 coinfection may reflect different population dynamics.