CLINICAL OUTCOME AND PREDICTIVE FACTORS OF FAILURE OF HIGHLY-ACTIVE ANTIRETROVIRAL THERAPY IN ANTIRETROVIRAL-EXPERIENCED PATIENTS IN ADVANCED STAGES OF HIV-1 INFECTION

Objective: To verify the effectiveness of highly active antiretroviral therapy (HAART) and to identify any factors predictive of clinical ou tcome in a clinical setting. Design: Observational study. Methods: Tre atment failure (i.e., the occurrence of new or recurrent AIDS-defining events, death or any definitive discontinuation) and the course of CD 4+ cell counts and HIV RNA copies were evaluated in 250 heavily pretre ated HIV-infected patients starting HAART [153 with indinavir (IDV), 5 5 with ritonavir (RTV), 43 with saquinavir (SQV)]. Univariate and mult ivariate analyses were performed to identify predictors of worse outco me. Results: During a median follow-up of 8 months, 75 patients (30%) had treatment failure because of the occurrence of an AIDS-defining ev ent or death (n = 24), inefficacy (n = 24), or severe intolerance (n = 27). Twenty new and six recurrent AIDS-defining events, and nine deat hs occurred (six out of 20 AIDS-defining events and two out of nine de aths within 1 month of treatment). CD4+ counts were above 200 x 10(6)/ l at AIDS diagnosis in only two patients. None of the SQV patients, 12 (7.8%) of the IDV patients, and 15 (27.3%) of the RTV-treated patient s were considered non-compliant. The SQV-containing regimens independe ntly correlated with treatment failure (relative risk, 2.46; 95% confi dence interval, 1.20-5.03; versus IDV). Low compliance partially deter mined outcome in RTV-treated patients; both severe immunodepression an d AIDS at baseline were predictive of treatment failure. There was a 1 0-fold increase in CD4+ cell counts in the patients treated with IDV a nd RTV; the best virological outcome occurred in IDV-treated patients, with 68.4% of patients showing undetectable HIV RNA copies after 6 mo nths. Conclusions: HAART was effective in 70% of patients; low complia nce and previous AIDS diagnosis represented predictive factors of ther apy failure. (C) 1998 Lippincott Williams & Wilkins.