Genotypic resistance profiles in antiretroviral-naive HIV-1 infections before and after initiation of first-line HAART: impact of polymorphism on resistance to therapy.
Genotypic testing using TRUGENE was performed for treatment-naive, human immunodeficiency virus type 1 (HIV-1)-infected patients at baseline and after initiation of protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) regimens. The genetic diversity of HIV-1 pol sequences from 92 CRF01_AE and 21 B strains was compared. Subsequently, the impact of polymorphism on resistance to therapy was studied in CRF01_AE-infected (n=29) and subtype B-infected (n=14) patients. At baseline, the differences between CRF01_AE and B strain were mainly observed in the minor mutations L10I/V, M36I and L63P/I/H (P<0.001, chi(2)). In the reverse transcriptase sequence, M41L and T215Y/S were more common in patients infected with subtype B virus (P<0.05, chi(2)). Although all patients treated with PI-based HAART had pre-existing minor mutations, a low prevalence of resistance to PIs was observed (5/43; 11.6%). Moreover, major mutations (D30N and N88D) conferring resistance to PIs were found in patients infected with subtype B strain. In conclusion, polymorphisms at the protease region may not reduce PI susceptibility during treatment. However, this study also revealed the difference in natural mutations among subtypes, which may affect the manifestation of drug resistance.
Sukasem
Chonlaphat
C
Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Churdboonchart
Vina
V
Sukeepaisarncharoen
Wisut
W
Piroj
Wantanich
W
Inwisai
Tasanee
T
Tiensuwan
Montip
M
Chantratita
Wasun
W
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D019380:Anti-HIV Agents; D054302:pol Gene Products, Human Immunodeficiency Virus