A randomized, dose-finding study with didanosine plus stavudine versus didanosine alone in antiviral-naive, HIV-infected Thai patients

Objectives: To evaluate the safety and efficacy of four different regimens of didanosine (ddl) + stavudine (d4T) in HIV-infected Thais. Design: Prospective, open-label, randomized study. Methods: Patients were randomized to four regimens of high and low doses of ddl and d4T or to ddl alone. D4T was added to the ddl-alone arm after week 24. The duration of study was 48 weeks. Results: Seventy-eight patients were randomized (mean CD4 cell count, 255 x 10(6)/l; mean plasma HIV-1 RNA; 4.3 log(10) copies/ml). In the intent-to-t reat analysis, 78% of patients in the pooled combination arms and 20% of th e patients in the ddl alone arm (to which d4T was added after 24 weeks) sho wed plasma HIV-1 RNA < 500 copies/ml at week 24 (P < 0.001), and 59% versus 53% at week 48, respectively. In addition, the proportion of patients with < 50 HIV-1 RNA copies/ml was 13% versus 7% at week 24 (P = 0.5) and 17% ve rsus 20% at week 48 respectively. At week 24, median CD4 cell count increas es from baseline were 101 x 10(6)/l in the pooled combination versus 76 x 1 0(6)/l in the ddl alone arm (P = 0.78). Logistic regression modeling sugges ted a correlation between receiving high dose ddl and achieving HIV-1 RNA < 500 copies/ml at week 48 (P = 0.07). Conclusions: The d4T/ddl combination was superior to ddl alone in producing HIV-1 viral suppression. At week 48, > 60% of patients treated with this c ombination reached HIV-1 RNA levels < 500 copies/ml. Receiving high dose dd l but not d4T may correlate with a better viral suppression. (C) 2000 Lippi ncott Williams & Wilkins.