REDUCED SENSITIVITY TO SAQUINAVIR - AN UPDATE ON GENOTYPING FROM PHASE I II TRIALS/

A genotypic analysis of the HIV-1 proteinase was performed on clinical specimen obtained from patients after different periods of Saquinavir (SQV) treatment. Proteinase genes of integrated proviral DNA from PBM C were isolated by PCR, cloned and individual sequences were obtained. Genotypic resistance was defined by the Gly48 --> Val and Leu90 --> M et exchanges. Frequencies and kinetics of resistance development will be reported for phase I/II trials V13330. V13329, O13328 and ACTG229 i n patients on monotherapy or combination therapy with RT inhibitors. D ata from V13330 have been analysed in more detail for correspondence o f genotypic and phenotypic resistance and any correlation between resi stance and changes in plasma viral RNA load. Furthermore, we will disc uss the data from our extensive proteinase gene sequence collection wi th respect to mutational changes which would be indicative of resistan ce to other inhibitors of HIV-1 proteinase.