Influence of CD4+ T cell counts on viral evolution in HIV-infected individuals undergoing suppressive HAART

We analyzed the viral C2-V4 envelope diversity, glycosylation patterns, and d(S)/d(N) ratios of plasma HIV-1 in an attempt to better understand the complex interaction between viral quasispecies and the host-selective pressures pre- and post-HAART. Phylogenetic analysis of the envelope gene of five patients revealed monophyletic clustering in patients with higher CD4(+) T cell counts and sequence intermingling in those with lower CD4(+) T cells in relation to the stage of HAART. Our analyses also showed clear shifts in N-linked glycosylation patterns in patients with higher CD4(+) T cells, suggesting possible distinct immunological pressures pre- and post-HAART. The relative preponderance of synonymous/nonsynonymous changes in the envelope region suggested a positive selection in patients with higher CD4(+) T cells, whereas lack of evidence for positive selection was found in the patients with lower CD4(+) T cells. An exception to the last analysis occurred in the only patient who reached complete viral suppression, maybe due to drug pressure exerted over the pol gene that may obscure the immune pressure/selection at the envelope in this analysis. All these indications may suggest that even when HAART generates viral suppression, quasispecies evolve in the envelope gene probably resulting from host-selective pressure. (C) 2004 Elsevier Inc. All rights reserved.