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

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 192 cells/mm³ and 4.2 log copies/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.