Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline

Richard B. Markham, Wei Cinn Wang, Anton E. Weisstein, Zhe Wang, Alvaro Munoz, Alan Templeton, Joseph Margolick, David Vlahov, Thomas Quinn, Homayoon Farzadegan, Xiao Fang Yu

Research output: Contribution to journalArticlepeer-review

Abstract

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 non-progressors. 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.

Original languageEnglish (US)
Pages (from-to)12568-12573
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number21
DOIs
StatePublished - Oct 13 1998

ASJC Scopus subject areas

  • General

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