Changes in the human immunodeficiency virus V3 region that correspond with disease progression: a meta-analysis

In order to determine the changes in the human immunodeficiency virus type-1 (HIV-1) envelope that corresponds with disease progression, a meta-analysis of viral forms was performed using HIV-1 sequences obtained from GenBank. Studies were selected that included longitudinally derived V3 envelope region sequences from multiple time points along with CD4 values as a marker of disease progression. Studies with a total of 58 subjects, 327 time points, and 380,000 total amino acid residues were included in this meta-analysis. Changes at specific amino acid sites over the course of disease progression stages were analyzed. The most common specific changes were found at amino acid sites 324D to N, 306S/G to R, and 360N to R. Other sites had changes from one amino acid type to another including the appearance of a basic form at 327, a charged form at 319, and 320D/E changing to basic or neutral. The timing of these changes was contrasted to CD4 decline with changes at 324 and 327 appearing before and 306, 320, and 319 appearing after the initiation of CD4 decline.