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.
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.
Authors: Binshan Shi; Christina Kitchen; Barbara Weiser; Douglas Mayers; Brian Foley; Kimdar Kemal; Kathryn Anastos; Marc Suchard; Monica Parker; Cheryl Brunner; Harold Burger Journal: Virology Date: 2010-05-08 Impact factor: 3.616
Authors: Julie B Dumond; Rosa F Yeh; Kristine B Patterson; Amanda H Corbett; Byung Hwa Jung; Naser L Rezk; Arlene S Bridges; Paul W Stewart; Myron S Cohen; Angela D M Kashuba Journal: AIDS Date: 2007-09-12 Impact factor: 4.177
Authors: Kimdar S Kemal; Kathryn Anastos; Barbara Weiser; Christina M Ramirez; Qiuhu Shi; Harold Burger Journal: AIDS Res Hum Retroviruses Date: 2013-04-01 Impact factor: 2.205
Authors: Kartik K Venkatesh; Allison K DeLong; Rami Kantor; Stacey Chapman; Jessica Ingersoll; Jaclynn Kurpewski; Maria Pia De Pasquale; Richard D'Aquila; Angela M Caliendo; Susan Cu-Uvin Journal: J Womens Health (Larchmt) Date: 2013-03-26 Impact factor: 2.681
Authors: Marta Bull; Gerald Learn; Indira Genowati; Jennifer McKernan; Jane Hitti; David Lockhart; Kenneth Tapia; Sarah Holte; Joan Dragavon; Robert Coombs; James Mullins; Lisa Frenkel Journal: PLoS One Date: 2009-09-22 Impact factor: 3.240