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.


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


METHODS
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.
Sungkanuparph
Somnuek
S
Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. rasuy@mahidol.ac.th
Sukasem
Chonlaphat
C
Manosuthi
Weerawat
W
Wiboonchutikul
Surasak
S
Piyavong
Bucha
B
Chantratita
Wasun
W
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011725:Pyridines / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D013449:Sulfonamides; D019562:Viral Load
D019380:Anti-HIV Agents; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; C107201:tipranavir