Protease gene polymorphism in HIV-1-infected patients and response to therapy including a protease inhibitor.

Protease inhibitors (PIs) are recently introduced drugs that have improved the survival of HIV-infected patients when given in combination with two re verse transcriptase inhibitors. The HIV-1 protease gene is naturally highly polymorphic. Selection pressure due to IP use can result in major or minor resistance-associated mutations (RAMs). This study investigated whether pr esence before IP therapy of minor RAMs on the protease gene predicts the vi rological response. Of the 58 PI-naive patients included in the study, 12 h ad received two nucleoside reverse transcriptor inhibitors, 14 had received indinavir, 16 ritonavir, and 28 saquinavir-SGC. Viral load was measured on DO (prior to PI initiation) and at M3 and M6 (Roche Monitor 1.5 with 200 a nd 20 copies/ml as the thresholds). The protease gene was fully sequenced o n DO using the ABI 377 automatic sequencer after RNA amplification by neste d RT-PCR. None of the viral strains exhibited major mutations, but 57 of 58 (98%) had at least one minor mutation (median number of substitutions, 4), 60% had 1 to 4 substitutions, and 40% had 5 to 9 substitutions. Substituti ons seen with a prevalence > 20% were located at codons 15, 35, 37, 41, 63, and 77. Numbers of substitutions at M3 and M6 were not correlated with vir al load or the nature of the PI used, and neither were they significantly d ifferent between patients with more or fewer than 20 copies/ml. These data suggest that the protease genotype at PI initiation does not predict the ef ficacy of a regimen including a PI and is of no assistance in deciding whet her or not to include a PI in a triple combination regimen.