EFFICACY AND SAFETY OF STAVUDINE AND DIDANOSINE COMBINATION THERAPY IN ANTIRETROVIRAL-EXPERIENCED PATIENTS

Objectives: To assess the efficacy, tolerance, and safety of combinati on antiretroviral therapy with didanosine and stavudine in HIV-infecte d patients with CD4+ cell counts > 100 x10(6)/1 and HIV plasma RNA > 1 0(4) copies/ml previously treated with ether antiretroviral agents for at least 3 months. Design: In this open, multicentre, non-randomized, Phase II pilot study, adult patients were administered didanosine (20 0 mg twice daily) plus stavudine (40 mg twice daily) for 6 months. Pat ients for whom the first regimen had led to undetectable HIV RNA level s were offered a second 6-month course of treatment; those who had ach ieved insufficient immunological and virological gains in the first 6 months were given a new combination. Methods: Primary evaluation of ef ficacy was based on viral load measured by branched DNA second-generat ion testing (lower limit of detection, 500 copies/ml) and CD4+ cell co unts; secondary evaluations included AIDS-defining events and clinical side-effects. Results: Sixty-five patients with median prior antiretr oviral therapy of 24 months (65 with zidovudine, 29 with zalcitabine) were included in the study. At baseline, median CD4+ cell count was 19 8 x 10(6)/l and median plasma HIV RNA was 80 000 copies/ml (4.9 log(10 ) copies/ml). In this heavily pretreated population, an increase in th e mean CD4+ cell count was observed (+70 x 10(6)/l at 24 weeks). In ad dition, rapid and prolonged antiviral activity was seen, with a mean m aximal decrease of 1.1 log(10) copies/ml at week 4, a mean decrease of 0.89 log(10) copies/ml at week 24, and a plasma RNA viraemia < 500 co pies/ml achieved in 14% of patients at week 24. Conclusions: Combinati on therapy with stavudine and didanosine is safe and leads to a sustai ned antiviral effect, even in patients with prolonged prior antiretrov iral exposure and low CD4+ cell counts. (C) 1998 Lippincott Williams & Wilkins.