Impact of antiretroviral therapy on viral tropism in HIV-infected patients followed longitudinally for over 5 years

Abstract

Viral tropism plays a major role in HIV pathogenesis and may influence the activity of entry inhibitors. The impact of antiretroviral therapy use on the dynamics of viral tropism over time is still poorly understood. HIV co-receptor usage was determined longitudinally for over 5 years in 237 plasma specimens collected from 73 distinct HIV-1-infected drug-naive individuals, 42 of whom initiated antiretroviral therapy thereafter and 31 who remained untreated. Viral tropism was estimated genotypically using the phenotype predictor software webPSSM, considering as X4 virus populations those with pure X4 and dual/mixed X4/R5 variants. At baseline, the prevalence of X4 viruses was 3.2% and 14.6% in patients who remained untreated and in those who initiated antiretroviral therapy, respectively (P = 0.112). Mean plasma HIV-RNA was lower in the former compared with the latter (3.8 +/- 0.9 versus 4.5 +/- 0.9 log; P < 0.004), while conversely the mean CD4 count was greater in untreated than in those who had begun therapy (536 +/- 191 versus 278 +/- 192 cells/mm3; P < 0.001). During follow-up, switch in co-receptor use occurred overall in 26% of the study population, with no significant differences between the groups. Emergence of X4 viruses was significantly associated with lower CD4 counts regardless of antiretroviral treatment exposure. The use of antiretroviral therapy does not seem to influence the selection of X4 viruses, which mainly occur in patients with low CD4 counts.