We describe changes in HIV-1 viral load, CD4+ T cell percentage, and incidence of drug resistance and factors associated with drug resistance for 134 children receiving antiretroviral therapy (ART) for approximately 1 year in Abidjan. Between August 1998 and September 2003, ART was initiated for 395 HIV-infected children ages 0-15 years in the Côte d'Ivoire national drug access initiative. All 1-year samples with detectable HIV RNA >1000 copies/ml were tested for HIV-1 drug resistance and changes in viral load and CD4+ T cell counts were also determined. At treatment initiation, 80% of children had CD4+ T cell percentages <15% and a median viral RNA load of 5.6 log copies/ml. The median age at treatment initiation was 7 years with only 25% of patients less than 4 years of age. Of the 134 children receiving therapy, 72 (54%) had undetectable viral load. The estimated 1-year viral load decline was 1.9 log10 copies/ml and the CD4+ T cell percentage increase was 10.9%. The estimated 1-year cumulative probability for developing any class of drug resistance was 0.44 (95% CI, 0.35, 0.53). In a multivariate analysis, the magnitude of virologic response to therapy was inversely associated with development of drug resistance. Children with less CD4+ T cell rise from baseline values and the use of dual therapy were also associated with the development of drug resistance. Guidelines are needed for the treatment of pediatric HIV infection in Africa in order to minimize the occurrence of drug resistance and enhance better virologic, immunologic, and clinical outcomes.