Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naïve patients

J Clin Virol. 2011 Feb;50(2):156-61. doi: 10.1016/j.jcv.2010.10.001. Epub 2010 Nov 4.

Abstract

Background and objectives: Minority drug-resistant HIV-1 variants, undetected by conventional genotyping, may impair the outcome of antiretroviral therapy (ART). Thus, we retrospectively analyzed the prevalence of minority drug-resistant HIV-1 variants before ART in chronically HIV-1 infected patients initiating first-line therapy and assessed the impact on clinical outcome in the prospective German Truvada cohort.

Study design: Samples from 146 antiretroviral treatment-naïve patients were collected between April 2005 and August 2006. K65R, K103N, and M184V variants at low frequencies were detected by allele-specific real-time PCR.

Results: Minority drug-resistant HIV-1 variants were detected in 20/146 patients (13.7%): the M184V mutation in 12/146 patients (8.2%), the K103N mutation in 8/146 patients (5.5%), and the K65R mutation in 4/146 patients (2.7%). Four patients with the M184V mutation also harbored the K65R or the K103N mutation. The 12- and 24 months virological efficacy data revealed that the rate of treatment failure was not increased in the group of patients harboring minority drug-resistant HIV-1 variants prior to ART.

Conclusions: Minority drug-resistant HIV-1 variants can be frequently detected in treatment-naïve, chronically HIV-1 infected patients. Despite the presence of those mutations as minority variants before initiating ART, most of the patients were successfully treated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Drug Resistance, Viral / genetics*
  • Female
  • Genetic Variation
  • Genotype
  • Germany
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • Humans
  • Male
  • Mutation
  • Polymerase Chain Reaction
  • Treatment Outcome

Substances

  • Anti-HIV Agents