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Analysis of low-frequency mutations associated with drug resistance to raltegravir before antiretroviral treatment.

Publication ,  Journal Article
Liu, J; Miller, MD; Danovich, RM; Vandergrift, N; Cai, F; Hicks, CB; Hazuda, DJ; Gao, F
Published in: Antimicrob Agents Chemother
March 2011

Raltegravir is highly efficacious in the treatment of HIV-1 infection. The prevalence and impact on virologic outcome of low-frequency resistant mutations among HIV-1-infected patients not previously treated with raltegravir have not been fully established. Samples from HIV treatment-experienced patients entering a clinical trial of raltegravir treatment were analyzed using a parallel allele-specific sequencing (PASS) assay that assessed six primary and six secondary integrase mutations. Patients who achieved and sustained virologic suppression (success patients, n = 36) and those who experienced virologic rebound (failure patients, n = 35) were compared. Patients who experienced treatment failure had twice as many raltegravir-associated resistance mutations prior to initiating treatment as those who achieved sustained virologic success, but the difference was not statistically significant. The frequency of nearly all detected resistance mutations was less than 1% of viral population, and the frequencies of mutations between the success and failure groups were similar. Expansion of pre-existing mutations (one primary and five secondary) was observed in 16 treatment failure patients in whom minority resistant mutations were detected at baseline, suggesting that they might play a role in the development of drug resistance. Two or more mutations were found in 13 patients (18.3%), but multiple mutations were not present in any single viral genome by linkage analysis. Our study demonstrates that low-frequency primary RAL-resistant mutations were uncommon, while minority secondary RAL-resistant mutations were more frequently detected in patients naïve to raltegravir. Additional studies in larger populations are warranted to fully understand the clinical implications of these mutations.

Duke Scholars

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

March 2011

Volume

55

Issue

3

Start / End Page

1114 / 1119

Location

United States

Related Subject Headings

  • Raltegravir Potassium
  • Pyrrolidinones
  • Mutation
  • Microbiology
  • Humans
  • HIV Infections
  • Drug Resistance, Viral
  • Anti-HIV Agents
  • 3214 Pharmacology and pharmaceutical sciences
  • 3207 Medical microbiology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, J., Miller, M. D., Danovich, R. M., Vandergrift, N., Cai, F., Hicks, C. B., … Gao, F. (2011). Analysis of low-frequency mutations associated with drug resistance to raltegravir before antiretroviral treatment. Antimicrob Agents Chemother, 55(3), 1114–1119. https://doi.org/10.1128/AAC.01492-10
Liu, Jia, Michael D. Miller, Robert M. Danovich, Nathan Vandergrift, Fangping Cai, Charles B. Hicks, Daria J. Hazuda, and Feng Gao. “Analysis of low-frequency mutations associated with drug resistance to raltegravir before antiretroviral treatment.Antimicrob Agents Chemother 55, no. 3 (March 2011): 1114–19. https://doi.org/10.1128/AAC.01492-10.
Liu J, Miller MD, Danovich RM, Vandergrift N, Cai F, Hicks CB, et al. Analysis of low-frequency mutations associated with drug resistance to raltegravir before antiretroviral treatment. Antimicrob Agents Chemother. 2011 Mar;55(3):1114–9.
Liu, Jia, et al. “Analysis of low-frequency mutations associated with drug resistance to raltegravir before antiretroviral treatment.Antimicrob Agents Chemother, vol. 55, no. 3, Mar. 2011, pp. 1114–19. Pubmed, doi:10.1128/AAC.01492-10.
Liu J, Miller MD, Danovich RM, Vandergrift N, Cai F, Hicks CB, Hazuda DJ, Gao F. Analysis of low-frequency mutations associated with drug resistance to raltegravir before antiretroviral treatment. Antimicrob Agents Chemother. 2011 Mar;55(3):1114–1119.

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

March 2011

Volume

55

Issue

3

Start / End Page

1114 / 1119

Location

United States

Related Subject Headings

  • Raltegravir Potassium
  • Pyrrolidinones
  • Mutation
  • Microbiology
  • Humans
  • HIV Infections
  • Drug Resistance, Viral
  • Anti-HIV Agents
  • 3214 Pharmacology and pharmaceutical sciences
  • 3207 Medical microbiology