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Background:  Because of the relatively high cost of antiretroviral (ARV) medicines and lack of capacity for their administration, few HIV-infected children globally receive ARV treatment, and they progress rapidly to AIDS. This study was designed to test the hypothesis that dual nucleoside ARV therapy, with addition of hydroxyurea only for treatment failures, is as efficacious, better tolerated, safer and less expensive, than initiation of highly-active antiretroviral therapy (HAART) with 2 nucleoside drugs plus a non-nucleoside ARV agent. Enrollment in the study ended early as ARV therapy became available in Botswana, and the standard of care changed.

Methods:  The Botswana/Baylor Antiretroviral Assessment (BANA) trial is a 2-arm unblinded, randomized, prospective study comparing stavudine, didanosine, and nevirapine (arm 1) vs stavudine and didanosine (arm 2). Patients between the ages of 6 months and 12 years who had received ARV medications for 6 weeks or less were eligible to enroll. Children failing treatment were offered best available alternative therapy or adding hydroxyurea as a salvage agent (arm 2 only). This study was approved by the ethics board at all participating institutions.

Results:  We enrolled 74 patients in BANA, 35 in arm 1 (mean age 65 months) and 39 in arm 2 (mean age 71 months); 44% and 22% of subjects assigned to arm 1 and arm 2, respectively, were classified in CDC clinical category C (p = 0.26). Analyses of key variables revealed no significant differences between the study arms at baseline. Analyses of the percentage change over time were conducted to compare the study arms at 4, 12, 28, and 44 weeks. Arm 1 was found to have a significantly greater decrease in viral load at weeks 4, 12, and 28 (p ≤0.01). Arm 1 had significantly greater increases in CD4 count at 28 and 44 weeks (p ≤0.01). No significant differences were found over time with respect to CD4%, although the sample size was smaller due to missing data. The change in weight over time was not significantly different between the 2 study arms. Subjects in arm 1 had greater percentage increases in ALP at all 4 time points (p <0.05). Independent monitors’ reports on the conduct of the study were favorable.

Conclusions:  Treatment with two nucleosides, in the short term, may be clinically equivalent to HAART. Participants in the 2 arms had similar toxicity profiles. Implementing an ARV clinical trial and treatment program is feasible for children in Botswana.

Keywords: Antiretroviral therapy; Pediatrics; International