[Evaluation of mutations that confer resistance to nucleoside analogs and protease inhibitors in HIV-1-infected patients. Study Group on Resistance to Antiretroviral Agents].
Genotypes that confer drug resistance to reverse transcriptase inhibitors and protease inhibitors were evaluated in HIV-1 proviral DNA obtained from peripheral blood mononuclear cell samples. Fifty-three HIV-1-infected patients were studied, 19 of whom had not received antiretroviral treatment. In the other 34 patients, 9 had been treated with combinations of two reverse transcriptase inhibitors (AZT, ddI, d4T, 3TC) and 25 had been treated with triple antiretroviral therapy including a protease inhibitor (nelfinavir, indinavir, saquinavir, ritonavir). To determine the presence of mutations involved in the development of resistance to reverse transcriptase inhibitors a hybridization Microtiter assay was carried out. Mutations were detected in treated patients as well as in those without previous antiretroviral treatment, with the most frequent mutations being those that confer resistance to AZT, followed by those that develop cross-resistance to ddI/ddC and 3TC, which are the most commonly used drugs to date. No mutations were detected to any nucleoside analog in only 13 cases. To analyze the presence of mutations in the protease gene a dot-blot hybridization was carried out which included the mutations in codons 36, 82 and 90. Mutation 82 was detected in one case. Therefore, with the aim of determining the pattern of genotypic mutations in patients infected with HIV-1 and in order to make the best therapeutic choice, it would be recommended to consider carrying out genotypic resistance assays in clinical practice.
Martínez
G
G
Departamento de Inmunología, Microbiología y Parasitología, Facultad de Medicina y Odontología de la Universidad del País Vasco, Bilbao.
Sarría
L
L
Campelo
C
C
Merchán
A
A
Cisterna
R
R
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009705:Nucleosides / Q000494:pharmacology / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D009705:Nucleosides; D011480:Protease Inhibitors
Evaluación de mutaciones que confieren resistencia a análogos de nucleósidos e inhibidores de la proteasa en pacientes infectados por el VIH-1. El Grupo de Estudio de Resistencias a Antirretrovirales.