TY - JOUR
T1 - HIV-1 drug resistance in variants from the female genital tract and plasma
AU - Kemal, Kimdar Sherefa
AU - Burger, Harold
AU - Mayers, Douglas
AU - Anastos, Kathryn
AU - Foley, Brian
AU - Kitchen, Christina
AU - Huggins, Penelope
AU - Schroeder, Tamara
AU - Picchio, Gaston
AU - Back, Sara
AU - Gao, Wei
AU - Meyer, William A.
AU - Weiser, Barbara
N1 - Funding Information:
Financial support: National Institutes of Health (grants R01AI52015 and U01AI/ DE 35004).
PY - 2007/2/15
Y1 - 2007/2/15
N2 - 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.
AB - 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.
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U2 - 10.1086/510855
DO - 10.1086/510855
M3 - Article
C2 - 17230413
AN - SCOPUS:33846784099
SN - 0022-1899
VL - 195
SP - 535
EP - 545
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -
