PATTERNS OF HIV-1 EVOLUTION IN INDIVIDUALS WITH DIFFERING RATES OF CD4 T-CELL DECLINE

Evolution of HIV-1 env sequences was studied in 15 seroconverting inje ction drug users selected for differences in the extent of CD4 T cell decline. The rates of increase of either sequence diversity at a given visit or divergence from the first seropositive visit were both highe r in progressors than in nonprogressors. Viral evolution in individual s with rapid or moderate disease progression showed selection favoring nonsynonymous mutations, while nonprogressors with low viral loads se lected against the nonsynonymous mutations that might have resulted in viruses with higher levels of replication. For 10 of the 15 subjects no single variant predominated over time. Evolution away from a domina nt variant was followed frequently at a later time point by return to dominance of strains closely related to that variant. The observed evo lutionary pattern is consistent with either selection against only the predominant virus or independent evolution occurring in different env ironments within the host. Differences in the level to which CD4 T cel ls fall in a given time period reflect not only quantitative differenc es in accumulation of mutations, but differences in the types of mutat ions that pro,ide the best adaptation to the host environment.