PREDICTORS OF LONG-TERM RESPONSE TO PROTEASE INHIBITOR THERAPY IN A COHORT OF HIV-INFECTED PATIENTS

Objective: To assess the rate of long-term effectiveness and factors a ssociated with response to protease inhibitor therapy in a cohort of H IV-infected patients. Design and setting: Prospective, non-randomized study in a tertiary care centre. Patients: A total of 400 HIV-infected patients who started on protease inhibitor therapy (saquinavir, 28%; ritonavir, 26%; indinavir, 46%) from March 1996 to March 1997. Main ou tcomes measures: Long-term virological and immunological effectiveness were defined as HIV RNA levels below 200 copies/ml and CD4+ cell coun t increase greater than 100 x 10(6)/l, respectively, after 12 months o f therapy. Results: Fifty-seven per cent of patients had a prior AIDS- defining illness, and 91% had received nucleoside analogues for a medi an time of 28 months. Median CD4+ count was 86 x 10(6) cells/l and HIV RNA level was 4.46 log(10) copies/ml. The global rate of virological and immunological effectiveness at 1 year was 45 and 59%, respectively . In a logistic regression analysis, treatment failure was associated with higher baseline HIV load [relative risk (RR), 2.10; P < 0.01], pr ior antiretroviral therapy (RR, 2.07; P < 0.01), and use of saquinavir (RR, 1.55; P = 0.03), whereas a reduction of more than 1 log(10) in H IV load within the first 3 months on therapy was strongly associated w ith response (RR, 0.65; P < 0.01). There was no strict correlation bet ween virological and immunological effectiveness (r = -0.35; P = 0.01) . Conclusions: Nearly half of the patients maintain undetectable HIV l oad after 1 year of therapy, although important immunological benefit can be obtained in a greater proportion of patients. These data sugges t the use of the most potent antiretroviral therapy in pretreated pati ents with high HIV load, and the capacity of initial virological decli ne to predict the long-term outcome. (C) 1998 Lippincott-Raven Publish ers.