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

AbstractBACKGROUND:
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.
AuthorsSomnuek Sungkanuparph, Chonlaphat Sukasem, Weerawat Manosuthi, Surasak Wiboonchutikul, Bucha Piyavong, Wasun Chantratita
JournalJournal of clinical virology : the official publication of the Pan American Society for Clinical Virology (J Clin Virol) Vol. 43 Issue 3 Pg. 284-6 (Nov 2008) ISSN: 1386-6532 [Print] Netherlands
PMID18701346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-HIV Agents
  • Pyridines
  • Pyrones
  • Sulfonamides
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1
  • tipranavir
Topics
  • Adult
  • Anti-HIV Agents (pharmacology)
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral
  • Female
  • Genotype
  • HIV Infections (virology)
  • HIV Protease (genetics)
  • HIV-1 (drug effects, genetics, isolation & purification)
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense
  • Pyridines (pharmacology)
  • Pyrones (pharmacology)
  • Sulfonamides
  • Viral Load

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