Prevalence of HIV-1 polymerase gene mutations in pre-treated patients in Thailand.

ABSTRACT

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.