HIV-1 drug resistance in variants from the female genital tract and plasma.
BACKGROUND
Human immunodeficiency virus type 1 (HIV-1) drug-resistance mutations may arise in a fraction of viral variants, and these variants may differ between compartments, including the genital tract and blood.


METHODS
We studied 14 women with detectable HIV-1 in both the genital tract and plasma despite antiretroviral treatment. We obtained HIV-1 RNA sequences from 280 unique viral variants and then determined the resistance genotype and the predicted phenotype (Virtual Phenotype; Virco BVBA) of each variant.


RESULTS
Eight patients (57%) displayed mutations conferring high-level HIV-1 drug resistance. Although we observed differences in specific mutations among viral variants, 13 of the 14 women showed highly concordant HIV-1 genotypic and predicted phenotypic resistance patterns in the 2 compartments. In 1 patient, resistance mutations appeared only in plasma; all variants in her genital tract, which displayed a low viral load, were susceptible.


CONCLUSIONS
These data suggest that, for the majority of women, determination of HIV-1 drug resistance in the plasma will approximate the drug-resistance pattern in the genital tract. Analysis of individual variants enabled us to identify minority species bearing distinctive linked mutations, which may serve as a source of novel resistance genotypes. These data are relevant to clinical management and the evolution of drug resistance.
Kemal
Kimdar Sherefa
KS
Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA.
Burger
Harold
H
Mayers
Douglas
D
Anastos
Kathryn
K
Foley
Brian
B
Kitchen
Christina
C
Huggins
Penelope
P
Schroeder
Tamara
T
Picchio
Gaston
G
Back
Sara
S
Gao
Wei
W
Meyer
William A
WA
Weiser
Barbara
B
D000328:Adult; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005836:Genitalia, Female / Q000821:virology*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
D019380:Anti-HIV Agents; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease