Combination therapy with stavudine (d47) plus didanosine (ddI) in children with human immunodeficiency virus infection

Objectives. To evaluate the safety, tolerance, and antiviral activity of combination therapy with stavudine (d4T) plus didanosine (ddI) in symptomatic human immunodeficiency virus (HIV)-infected children. Methods. The study enrolled HIV-infected children who successfully completed Pediatric AIDS Clinical Trials Group (PACTG) protocol 240 (d4T versus zidovudine [ZDV] monotherapy) without disease progression or who had received ZDV monotherapy by prescription for at least the preceding 6 months. Children who had received d4T monotherapy in PACTG 240 were assigned to treatment with d4T plus ddI (arm 1). Children who had received ZDV monotherapy in PACTG 240 or by prescription were randomized in a double-blind manner to treatment with either d4T alone (arm 2) or d4T plus ddI (arm 3). patients were followed for 48 weeks each. Results, A total of 108 children were enrolled. The mean age was 5.0 years (range, 1.6 to 11.5 years), with mean baseline plasma HIV RNA concentration and CD4(+) lymphocyte count of 4.6 log(10) copies/mL (range, 2.6 to 5.9 log(10) copies/mL) and 819 cells/mu L (range, 8 to 3431 cells/mu L), respectively. Both d4T monotherapy and d4T plus ddI combination therapy were well-tolerated, with 96 (89%) patients completing 48 weeks of study treatment. Plasma HIV RNA concentrations showed larger average declines in arm 3 compared with arm 2 at study week 12 (0.49 vs 0.18 log(10) copies/mL, respectively); these average declines were maintained through week 48 (0.51 vs 0.17 log(10) copies/mL, respectively). Fewer than 8% of the patients in any of the treatment arms had plasma HIV RNA concentrations below the limit of quantification (200 copies/mL) at any time point. Conclusions. Combination therapy with d4T plus ddI is safe and well-tolerated in HIV-infected children, producing durable, but incomplete, suppression of virus replication. This combination of nucleoside antiretroviral agents may provide a valuable backbone to protease inhibitor-containing treatment regimens for HIV-infected children.