Evolution and recombination of genes encoding HIV-1 drug resistance and tropism during antiretroviral therapy.
Characterization of residual plasma virus during antiretroviral therapy (ART) is a high priority to improve understanding of HIV-1 pathogenesis and therapy. To understand the evolution of HIV-1 pol and env genes in viremic patients under selective pressure of ART, we performed longitudinal analyses of plasma-derived pol and env sequences from single HIV-1 genomes. We tested the hypotheses that drug resistance in pol was unrelated to changes in coreceptor usage (tropism), and that recombination played a role in evolution of viral strains. Recombinants were identified by using Bayesian and other computational methods. High-level genotypic resistance was seen in approximately 70% of X4 and R5 strains during ART. There was no significant association between resistance and tropism. Each patient displayed at least one recombinant encompassing env and representing a change in predicted tropism. These data suggest that, in addition to mutation, recombination can play a significant role in shaping HIV-1 evolution.
Shi
Binshan
B
Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA.
Kitchen
Christina
C
Weiser
Barbara
B
Mayers
Douglas
D
Foley
Brian
B
Kemal
Kimdar
K
Anastos
Kathryn
K
Suchard
Marc
M
Parker
Monica
M
Brunner
Cheryl
C
Burger
Harold
H
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D016000:Cluster Analysis; D024882:Drug Resistance, Viral; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011995:Recombination, Genetic; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014764:Viral Proteins / Q000235:genetics*; D056189:Viral Tropism / Q000187:drug effects*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D019380:Anti-HIV Agents; D014764:Viral Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus
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