Prevalence of HIV-1 polymerase gene mutations in pre-treated patients in Thailand.
To determine the prevalence of drug resistance-conferring mutations in human immunodeficiency virus type 1 (HIV-1), 83 HIV-1 infected Thai patients who had been treated with any antiretroviral drug were studied. HIV-1 RNA was reverse transcribed and amplified by RT-PCR. The direct sequencing of HIV-1 reverse transcriptase (RT) and protease was then performed. Changes in nucleotide and amino acid sequences were determined by comparison with a pNL4-3 reference sequence. Data on mutations associated with resistance to antiretroviral drugs were obtained from literature. The mutations associated with lamivudine resistance (M184V/I) were found most often (in 45.7% of individuals). Zidovudine-resistant mutants: T215Y/F (36%), M41L (28%) and K70R (25.3%) were common; but mutations linked to didanosine (L74V) and multinucleoside-resistant genotypes (Q151M) were rarely recognized (2.4% and 3.6%, respectively). The stavudine-resistant mutant (V75T) and T69 insertions were not found. All subjects who had a significant exposure to antiretroviral drugs and current virological failure in the past carried drug-resistant genotypes. Genotypic resistance to zidovudine, lamivudine, zalcitabine, indinavir and ritonavir appeared in more than one third of the samples, which suggested that the prevalence of the HIV-1 resistance-conferring genotype resisting reverse transcriptase inhibitors and/or protease inhibitors was high in treatment experienced patients.
Chantratita
Wasun
W
Department of Pathology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. rawct@mahidol.ac.th
Jenwitheesuk
Ekachai
E
Watitpun
Chotip
C
Pongthanapisith
Viroj
V
Vibhagool
Asda
A
Leechawengwong
Manoon
M
Sookpranee
Mondej
M
Apairatana
Anantasak
A
D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D024882:Drug Resistance, Viral / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013785:Thailand
D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D012321:DNA-Directed RNA Polymerases; D016333:HIV Protease