Recombination between variants from genital tract and plasma: evolution of multidrug-resistant HIV type 1.

AIDS Research and Human Retroviruses
Kimdar Sherefa KemalBarbara Weiser

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.

References

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Citations

Mar 6, 2013·AIDS Research and Human Retroviruses·Kimdar S KemalHarold Burger
May 23, 2015·Retrovirology·Bernard S BagayaYong Gao
Jan 8, 2015·Current Opinion in HIV and AIDS·Séverine Vuilleumier, Sebastian Bonhoeffer
Dec 17, 2014·Journal of Clinical Microbiology·Suzanne EdwardsUNKNOWN Swiss HIV Cohort Study
Oct 15, 2013·Emerging Health Threats Journal·Cyril C Y YipKwok-Yung Yuen

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Methods Mentioned

BETA
lavage
PCR

Software Mentioned

GARD
PhenoTecT
deCIPhR
BLAST
InPheno
SimPlot

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