Efficacy and safety of stavudine plus didanosine in asymptomatic HIV-infected children with plasma HIV RNA below 50,000 copies per milliliter

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Abstract
BACKGROUND: Simple antiretroviral drug combinations might provide a comparable benefit to standard triple regimens in patients with mild HIV disease, because poor adherence and toxicities often compromise the sustained benefit of the latest triple regimens, especially when protease inhibitors are used. Bad adherence is the main cause of virological failure in HIV-positive children. The activity and safety of a double combination of nucleosides with high genetic barrier for resistance (stavudine plus didanosine) was assessed in children with nonadvanced HIV disease. METHOD: From February 1998 to March 1999, 16 children were enrolled in six Spanish hospitals in a trial in which didanosine (180 mg/m2/day) and stavudine (2 mg/Kg/day) were administered for 48 weeks to asymptomatic naive children with plasma HIV RNA below 50,000 copies/mL and CD4 counts above 15%. Genotypic resistance to nucleoside analogues was examined at baseline and at the end of the study. RESULTS: At baseline, median age was 6.5 years (range, 2-14). The absolute and percentage mean CD4 counts were 864 and 32%, respectively (z score: -0.48 and -1.1). Mean plasma viral load was 4.05 log. No clinical events occurred during the 1-year study period. Minor side effects were recorded in two thirds of children, although none led to drug discontinuation. Lipoatrophy was not recognized in any of the participants. Plasma HIV RNA below 400 copies/mL was reached by 43% and 44% of patients at 24 and 48 weeks, respectively. The z score for absolute and percentage CD4 count increased significantly at 48 weeks (+0.63 and +0.97, respectively) in respect to baseline (p < .05). Resistance mutations linked to didanosine (L74V or M184V) or stavudine (V75T) were not recognized and neither were multinucleoside resistant genotypes (151 complex or 69 inserts). However, four children developed AZT-like mutations T215Y and/or M41L. CONCLUSION: Treatment with a dual combination of didanosine plus stavudine in naive children with nonadvanced HIV disease is safe and provides a satisfactory virological outcome at 1 year. Toxicity and drug resistance seem to occur rarely when this combination is used, which allows good adherence and spares other future treatment options.