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

8 Citations (Scopus)

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

Fingerprint

Genetic Recombination
HIV-1
Nevirapine
Lamivudine
Zidovudine
Viral Genome
Therapeutics
Point Mutation
Drug Resistance
Genome
Viruses
Genes

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Kemal, K. S., Ramirez, C. M., Burger, H., Foley, B., Mayers, D., Klimkait, T., ... 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

Recombination between variants from genital tract and plasma : Evolution of multidrug-resistant HIV type 1. / Kemal, Kimdar S.; Ramirez, Christina M.; Burger, Harold; Foley, Brian; Mayers, Douglas; Klimkait, Thomas; Hamy, François; Anastos, Kathryn; Petrovic, Katarina; Minin, Vladimir N.; Suchard, Marc A.; Weiser, Barbara.

In: AIDS Research and Human Retroviruses, Vol. 28, No. 12, 01.12.2012, p. 1766-1774.

Research output: Contribution to journalArticle

Kemal, KS, Ramirez, CM, Burger, H, Foley, B, Mayers, D, Klimkait, T, Hamy, F, Anastos, K, Petrovic, K, Minin, VN, Suchard, MA & Weiser, B 2012, 'Recombination between variants from genital tract and plasma: Evolution of multidrug-resistant HIV type 1', AIDS Research and Human Retroviruses, vol. 28, no. 12, pp. 1766-1774. https://doi.org/10.1089/aid.2011.0383
Kemal, Kimdar S. ; Ramirez, Christina M. ; Burger, Harold ; Foley, Brian ; Mayers, Douglas ; Klimkait, Thomas ; Hamy, François ; Anastos, Kathryn ; Petrovic, Katarina ; Minin, Vladimir N. ; Suchard, Marc A. ; Weiser, Barbara. / Recombination between variants from genital tract and plasma : Evolution of multidrug-resistant HIV type 1. In: AIDS Research and Human Retroviruses. 2012 ; Vol. 28, No. 12. pp. 1766-1774.
@article{334b7e79f77947b0b5574c79492c3c39,
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.",
author = "Kemal, {Kimdar S.} and Ramirez, {Christina M.} and Harold Burger and Brian Foley and Douglas Mayers and Thomas Klimkait and Fran{\cc}ois Hamy and Kathryn Anastos and Katarina Petrovic and Minin, {Vladimir N.} and Suchard, {Marc A.} and Barbara Weiser",
year = "2012",
month = "12",
day = "1",
doi = "10.1089/aid.2011.0383",
language = "English (US)",
volume = "28",
pages = "1766--1774",
journal = "AIDS Research and Human Retroviruses",
issn = "0889-2229",
publisher = "Mary Ann Liebert Inc.",
number = "12",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84869986611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869986611&partnerID=8YFLogxK

U2 - 10.1089/aid.2011.0383

DO - 10.1089/aid.2011.0383

M3 - Article

C2 - 22364185

AN - SCOPUS:84869986611

VL - 28

SP - 1766

EP - 1774

JO - AIDS Research and Human Retroviruses

JF - AIDS Research and Human Retroviruses

SN - 0889-2229

IS - 12

ER -