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

Journal Article (Clinical Trial, Phase III;Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Liu, J; Miller, MD; Danovich, RM; Vandergrift, N; Cai, F; Hicks, CB; Hazuda, DJ; Gao, F

Published Date

  • March 2011

Published In

Volume / Issue

  • 55 / 3

Start / End Page

  • 1114 - 1119

PubMed ID

  • 21173185

Pubmed Central ID

  • PMC3067114

Electronic International Standard Serial Number (EISSN)

  • 1098-6596

Digital Object Identifier (DOI)

  • 10.1128/AAC.01492-10


  • eng

Conference Location

  • United States