TY - JOUR
T1 - Recombination between variants from genital tract and plasma
T2 - Evolution of multidrug-resistant HIV type 1
AU - Kemal, Kimdar S.
AU - Ramirez, Christina M.
AU - Burger, Harold
AU - Foley, Brian
AU - Mayers, Douglas
AU - Klimkait, Thomas
AU - Hamy, François
AU - Anastos, Kathryn
AU - Petrovic, Katarina
AU - Minin, Vladimir N.
AU - Suchard, Marc A.
AU - Weiser, Barbara
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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.
AB - 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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U2 - 10.1089/aid.2011.0383
DO - 10.1089/aid.2011.0383
M3 - Article
C2 - 22364185
AN - SCOPUS:84869986611
SN - 0889-2229
VL - 28
SP - 1766
EP - 1774
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
IS - 12
ER -