Effect of HIV/HCV Co-Infection on the Protease Evolution of HIV-1B: A Pilot Study in a Pediatric Population.

Abstract

This pilot study evaluates in pediatric patients the impact of HIV/HCV coinfection in the molecular evolution of the HIV-1 subtype B protease (HIV-1BPR). For this study, HIV-1B/HCV coinfected (15) and HIV-1B monoinfected (56) patients with available HIV-1B pol sequences were enrolled. Both groups of patients had comparable gender frequencies and average age, time of infection, antiretroviral treatment (ART) exposure and time under ART. Prevalence of drug resistance mutations (DRM), genetic diversity, number of synonymous (dS) and non-synonymous (dN) mutations per site and selection pressures (dN - dS) in the HIV-1BPR were estimated and compared between mono- and coinfected patients. Both HIV-1B populations presented similar genetic diversity (0.050 ± 0.02 vs. 0.045 ± 0.01) and dS (0.074 ± 0.03 vs. 0.078 ± 0.04). In turn, in coinfected patients the HIV-1BPR had higher dN (0.045 ± 0.01 vs. 0.024 ± 0.01) and dN-dS (-0.026 ± 0.02 vs. -0.048 ± 0.04) values, and less amino acid sites under purifying selection (4.2% vs. 42.1%) than in monoinfected patients. Accordingly, in co-infection with HCV, the HIV-1BPR sites 50, 53, 82, 84 and 88 - associated with resistance to PIs - were under neutral evolution, whereas these sites were under purifying selection in monoinfected patients. This pilot study suggests that HIV-1B may evolve differently in the presence than in the absence of HCV.