FACTORS INFLUENCING THE EMERGENCE OF RESISTANCE TO INDINAVIR - ROLE OF VIROLOGICAL, IMMUNOLOGICAL, AND PHARMACOLOGICAL VARIABLES

A major problem with the use of human immunodeficiency virus type 1 (H IV-1) protease inhibitors as monotherapy has been an unacceptably high rate of emergence of resistance. To examine possible influences on th e time to emergence of resistance, 24-week data were examined from fiv e studies in which indinavir had been administered as monotherapy or a s a component of combination therapy. Monotherapy data indicated a cor relation between the level of HIV-1 RNA achieved and the risk of emerg ence of resistance: the lower the level, the lower the risk. When comb ination and monotherapy regimens were compared, the group receiving in dinavir + lamivudine + zidovudine had a significantly lower risk of re sistance, even after adjusting for the minimum HIV-1 RNA level achieve d. The findings indicate that if at all possible, HIV-1-infected patie nts should receive combination chemotherapy to minimize the emergence of resistance to the protease inhibitor portion of the regimen. The go al of therapy should be to decrease the HIV-1 RNA load to a less-than- detectable level.