Prevalence of HIV-1 drug resistance in antiretroviral-naive pregnant Thai women.

HIV-1 drug resistance may limit the use of antiretrovirals when attempting to reduce the vertical transmission rate. Establishing the prevalence of the HIV-1 mutations associated with antiretroviral resistance in pregnant women will enable clinicians to maximize the chances of preventing vertical transmission. In order to determine the prevalence of HIV-1 resistant strains among antiretroviral-naive pregnant Thai women, the nucleotide sequences of the HIV-1 polymerase (pol) gene were evaluated. The plasma samples were collected from the women during the 34th week of pregnancy: numerous secondary mutations could be found in the reverse transcriptase (RT) and protease gene, while no primary mutations in the pol gene were found. The result also showed that by detecting the delta32bp deletion within the CCR 5 locus, it was evident that none of HIV-1 infected individuals had homozygous or heterozygous delta32bp deletions of the CCR5 gene; moreover, no CCR5 gene mutations were found in any individual.

The effects of antiretroviral dose modification on the re-emergence of HIV-1 wild-type strains.

Four human immunodeficiency virus type 1 (HIV-1) treatment-naïve Thai patients began antiretrovival therapy with a triple drug regimen -zidovudine plus lamivudine plus indinavir; this regimen was modified at week 20 of therapy because of drug toxicity. The virus in all patients was suppressed to lower than 400 copies/ml while they were taking the triple antiretroviral drug regimen. However, suppression was lost after changing the antiretroviral regimen. A comparison of HIV-1 DNA sequences taken from the baseline (day 0) and week 24 showed no significant overgrowth in HIV-1 drug-resistant strains. There was no difference in the protease and reverse transcriptase (RT) mutation profiles. Resistant variants did not emerge, even after sub-therapeutic levels of antiretroviral drugs had been introduced to these patients for 4 weeks. These findings may have clinical implications for long-term treatment strategies.

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.