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

Kimdar S. Kemal, Christina M. Ramirez, Harold Burger, Brian Foley, Douglas Mayers, Thomas Klimkait, François Hamy, Kathryn Anastos, Katarina Petrovic, Vladimir N. Minin, Marc A. Suchard, Barbara Weiser

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1766-1774
Number of pages9
JournalAIDS Research and Human Retroviruses
Volume28
Issue number12
DOIs
StatePublished - Dec 1 2012

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ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Kemal, K. S., Ramirez, C. M., Burger, H., Foley, B., Mayers, D., Klimkait, T., Hamy, F., Anastos, K., Petrovic, K., Minin, V. N., Suchard, M. A., & Weiser, B. (2012). Recombination between variants from genital tract and plasma: Evolution of multidrug-resistant HIV type 1. AIDS Research and Human Retroviruses, 28(12), 1766-1774. https://doi.org/10.1089/aid.2011.0383