Drug resistance in patients experiencing early virological failure under atriple combination including indinavir

Objective: To assess the pattern of drug resistance mutations selected in H IV-1-infected patients failing a first line triple combination therapy incl uding 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 fo r the presence of drug-resistant genotypes. Results: The mean level of plasma viraemia at rebound was 7824 HIV-1 RNA co pies/ 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 seque nce analysis yielded results for 51 (70%) of the patients having good adher ence. More than half of them (26/51, 51%) carried primary mutations associa ted 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-re sistant viruses at all. The most frequent drug-resistant genotypes in the r everse 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 p atients. Conclusion: The overall rate of drug-resistant HIV genotypes was 38% (28/73 ) in patients with good adherence and who were experiencing a first virolog ical failure under a triple combination regimen including indinavir; resist ance 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 limit ed to these compounds, might be justified. (C) 2001 Lippincott Williams & W ilkins.