Sequence analysis of the HIV-1 protease coding region of 18 HIV-1-infected patients prior to HAART and possible implications on HAART

Background: The majority of HIV-infected patients are treated with highly active antiretroviral therapy (HAART) consisting of a combination of inhibitors of the protease (PIs) and the reverse transcriptase (RTIs). Analysis of mutations within these enzymes which are associated with development of resistance to the applied inhibitors is of major clinical importance. In particular, pre-existing mutations in previously untreated individuals may adversely influence the efficacy of HAART. Objectives: The sequences of the protease coding regions of 18 HIV-1-infected patients were analysed prior to HAART. Study design: DNA was extracted from whole blood samples of HIV-1-infected treatment-naive patients. The protease coding region was amplified by nested PCR and sequenced directly. The resulting amino acid substitutions were analysed for known mutations associated with known resistance to PIs, Results: In all 18 analysed individuals we found 1-10 amino acid substitutions per patient in their HIV-1 protease coding region. These mutations occurred altogether at 27 positions of the 99 amino acids of the protease coding region. Seven of these mutated positions are associated with described resistance to PIs. Altogether, 15 of the 18 patients (83%) carried at least one such resistance-conferring: alteration in their protease coding region. All patients are currently followed up during their present therapy to detect possible resistance formation to the applied PIs. Conclusions: A large variety of pre-existing mutations associated with resistance to PIs was observed prior to their treatment. As none of the patients ever received HAART before and infection with resistant viral strains is very unlikely, these amino acid substitutions evidently reflect natural polymorphism of the HIV-1 protease coding region. (C) 2000 Elsevier Science B.V. All rights reserved.