title: Recombination between variants from genital tract and plasma: evolution of multidrug-resistant HIV type 1.
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.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY, USA.
authors.forename: Kimdar S
authors.initials: KS
authors.lastname: Kemal
authors.forename: Christina M
authors.initials: CM
authors.lastname: Ramirez
authors.forename: Harold
authors.initials: H
authors.lastname: Burger
authors.forename: Brian
authors.initials: B
authors.lastname: Foley
authors.forename: Douglas
authors.initials: D
authors.lastname: Mayers
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.forename: François
authors.initials: F
authors.lastname: Hamy
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Katarina
authors.initials: K
authors.lastname: Petrovic
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Minin
authors.forename: Marc A
authors.initials: MA
authors.lastname: Suchard
authors.forename: Barbara
authors.initials: B
authors.lastname: Weiser
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D005260:Female; D005836:Genitalia, Female / Q000821:virology*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008969:Molecular Sequence Data; D019829:Nevirapine / Q000008:administration & dosage; D010949:Plasma / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine