Tipranavir resistance associated mutations in protease inhibitor-naïve patients with HIV-1 subtype A/E infection

J Clin Virol. 2008 Nov;43(3):284-6. doi: 10.1016/j.jcv.2008.07.002. Epub 2008 Aug 13.

Abstract

Background: Tipranavir-resistance associated mutations (TPV-RAMs) are often observed among patients with HIV-1 subtype A/E infection. Data regarding TPV resistance in subtype A/E is still limited.

Objectives: To determine the prevalence of TPV-RAMs among protease inhibitor-naïve, HIV-1 subtype A/E infected patients.

Study design: Genotypic resistance testing was conducted among HIV-1-infected patients who were PI-naïve.

Results: We studied 112 patients (mean age, 40.7 years; 58% male). Median CD4 cell count and HIV-1 RNA were 192cells/mm(3) and 4.2logcopies/mL, respectively. Ninety-three patients (83%) infected with subtype A/E; the others had subtype B. The most common TPV-RAMs were M36I (88%), H69K (61%), and I13V (48%). Median number of TPV-RAMs was 3 mutations. Patients with subtype A/E had higher prevalence of I13V (54% vs. 21%, P=0.011), M36I (96% vs. 53%, P<0.001), H69K (68% vs. 26%, P=0.001), and >2 TPV-RAMs (62% vs. 21%, P=0.002). In multivariate analysis, only subtype A/E was associated with the occurrence of >2 TPV-RAMs (OR 9.83; 95%CI, 1.95-39.57; P=0.006).

Conclusions: TPV-RAMs previously described by IAS-USA are commonly observed in PI-naïve patients with HIV-1 subtype A/E infection. Further studies to define virologic response of subtype A/E to TPV and clinical validation of TPV-RAMs in HIV-1 subtype A/E are essentially needed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology*
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral
  • Female
  • Genotype
  • HIV Infections / virology*
  • HIV Protease / genetics*
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Pyridines / pharmacology*
  • Pyrones / pharmacology*
  • Sulfonamides
  • Viral Load

Substances

  • Anti-HIV Agents
  • Pyridines
  • Pyrones
  • Sulfonamides
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1
  • tipranavir