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Journal of Virology, July 2005, p. 9006-9018, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.9006-9018.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Changes in Human Immunodeficiency Virus Type 1 Fitness and Genetic Diversity during Disease Progression

Division of Infectious Diseases, Department of Medicine,¹ Molecular Virology Program, Case Western Reserve University, Cleveland, Ohio 44106,² Laboratory of Immunology, Institute of Tropical Medicine, Antwerp, Belgium,³ Department of Microbiology, University of Washington, Seattle, Washington⁴

Received 10 September 2004/ Accepted 27 February 2005

This study examined the relationship between ex vivo human immunodeficiency virus type 1 (HIV-1) fitness and viral genetic diversity during the course of HIV-1 disease. Primary HIV-1 isolates from 10 patients at different time points were competed against control HIV-1 strains in peripheral blood mononuclear cell (PBMC) cultures to determine relative fitness values. Patient HIV-1 isolates sequentially gained fitness during disease at a significant rate that directly correlated with viral load and HIV-1 env C2V3 diversity. A loss in both fitness and viral diversity was observed upon the initiation of antiretroviral therapy. A possible relationship between genotype and phenotype (virus replication efficiency) is supported by the parallel increases in ex vivo fitness and viral diversity during disease, of which the correlation is largely based on specific V3 sequences. Syncytium-inducing, CXCR4-tropic HIV-1 isolates did have higher relative fitness values than non-syncytium-inducing, CCR5-tropic HIV-1 isolates, as determined by dual virus competitions in PBMC, but increases in fitness during disease were not solely powered by a gradual switch in coreceptor usage. These data provide in vivo evidence that increasing HIV-1 replication efficiency may be related to a concomitant increase in HIV-1 diversity, which in turn may be a determining factor in disease progression.

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