Recombination Between Variants from Genital Tract and Plasma: Evolution of Multidrug-resistant HIV Type 1

Overview

Journal AIDS Res Hum Retroviruses

Publisher Mary Ann Liebert

Specialty Infectious Diseases

Date 2012 Feb 28

PMID 22364185

Citations 4

Authors

Kimdar S Kemal

Christina M Ramirez

Harold Burger

Brian Foley

Douglas Mayers

Thomas Klimkait

Francois Hamy

Kathryn Anastos

Katarina Petrovic

Vladimir N Minin

Marc A Suchard

Barbara Weiser

Affiliations

Soon will be listed here.

Abstract

Multidrug-resistant (MDR) HIV-1 presents a challenge to the efficacy of antiretroviral therapy (ART). To examine mechanisms leading to MDR variants in infected individuals, we studied recombination between single viral genomes from the genital tract and plasma of a woman initiating ART. We determined HIV-1 RNA sequences and drug resistance profiles of 159 unique viral variants obtained before ART and semiannually for 4 years thereafter. Soon after initiating zidovudine, lamivudine, and nevirapine, resistant variants and intrapatient HIV-1 recombinants were detected in both compartments; the recombinants had inherited genetic material from both genital and plasma-derived viruses. Twenty-three unique recombinants were documented during 4 years of therapy, comprising ~22% of variants. Most recombinant genomes displayed similar breakpoints and clustered phylogenetically, suggesting evolution from common ancestors. Longitudinal analysis demonstrated that MDR recombinants were common and persistent, demonstrating that recombination, in addition to point mutation, can contribute to the evolution of MDR HIV-1 in viremic individuals.

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