Drug resistance in patients experiencing early virological failure under a triple combination including indinavir.

Published

Journal Article

OBJECTIVE:To assess the pattern of drug resistance mutations selected in HIV-1-infected patients failing a first line triple combination therapy including indinavir. PATIENTS AND METHODS:Plasma samples from 87 patients collected at the time of the first virological rebound (> 50 HIV-RNA copies/ml) were examined for the presence of drug-resistant genotypes. RESULTS:The mean level of plasma viraemia at rebound was 7824 HIV-1 RNA copies/ml in 73 subjects with good compliance, whereas it was 359,460 HIV-1 RNA copies/ml in 14 patients who admitted to poor adherence. Genetic sequence analysis yielded results for 51 (70%) of the patients having good adherence. More than half of them (26/51, 51%) carried primary mutations associated with resistance to nucleoside analogues. In contrast, primary protease inhibitor resistance mutations were recognized less frequently (14/51, 27%; P < 0.05). Moreover, in 23 (45%) patients there was no evidence of drug-resistant viruses at all. The most frequent drug-resistant genotypes in the reverse transcriptase gene were at codons 184 (n = 19), 215 (n = 14) and 41 (n = 8), whereas for the protease they were at codons 46 (n = 10), 82 (n = 9) and 90 (n = 7). No resistance genotypes were found among non-compliant patients. CONCLUSION:The overall rate of drug-resistant HIV genotypes was 38% (28/73) in patients with good adherence and who were experiencing a first virological failure under a triple combination regimen including indinavir; resistance to nucleoside analogues was more frequent than resistance to indinavir. Therefore, treatment intensification in those patients without resistance, or a selective substitution of nucleosides in those with resistance limited to these compounds, might be justified.

Full Text

Cited Authors

  • Gallego, O; de Mendoza, C; Pérez-Elías, MJ; Guardiola, JM; Pedreira, J; Dalmau, D; Gónzalez, J; Moreno, A; Arribas, JR; Rubio, A; García-Arata, I; Leal, M; Domingo, P; Soriano, V

Published Date

  • September 2001

Published In

Volume / Issue

  • 15 / 13

Start / End Page

  • 1701 - 1706

PubMed ID

  • 11546946

Pubmed Central ID

  • 11546946

Electronic International Standard Serial Number (EISSN)

  • 1473-5571

International Standard Serial Number (ISSN)

  • 0269-9370

Digital Object Identifier (DOI)

  • 10.1097/00002030-200109070-00014

Language

  • eng