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V3 envelope sequences were determined from amplified human immunodeficiency virus type 1 (HIV-1) sequences of uncultivated leukocytes obtained sequentially from four infected adults over the course of infection. Lower levels of sequence heterogeneity were noted in samples obtained early in IIV-1 infection, prior to CD4 depletion, than in samples obtained at later times during disease. The pattern of amino acid sequence divergence included nonrandom changes, with evidence of sequence variants arising from HIV-1 quasi-species present earlier in infection. Consensus sequences for isolates obtained early after infection from different patients demonstrated a high level of conservation with one another and a consensus sequence for macrophage-tropic HIV-1 isolates.These findings suggest that a highly r subset of HIV-1 quasi-species can be transmitted and can establish infection.

Evolution of HIV-1 env sequences was studied in 15 seroconverting injection 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 higher in progressors than in nonprogressors. Viral evolution in individuals with rapid or moderate disease progression showed selection favoring nonsynonymous mutations, while nonprogressors with low viral loads selected 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 dominant variant was followed frequently at a later time point by return to dominance of strains closely related to that variant. The observed evolutionary pattern is consistent with either selection against only the predominant virus or independent evolution occurring in different environments within the host. Differences in the level to which CD4 T cells fall in a given time period reflect not only quantitative differences in accumulation of mutations, but differences in the types of mutations that provide the best adaptation to the host environment.

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