Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients

PLoS One. 2012;7(6):e37983. doi: 10.1371/journal.pone.0037983. Epub 2012 Jun 18.


Background: Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naïve patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential.

Methods: To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥ 1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs.

Results: We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥ 4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥ 1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0-1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5-1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome.

Conclusions: The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Lymphocyte Count
  • Drug Resistance, Viral / genetics*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease / genetics*
  • HIV Protease Inhibitors / pharmacology*
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Male
  • Mutation*
  • RNA, Viral / blood
  • Viral Load


  • HIV Protease Inhibitors
  • RNA, Viral
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1