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Immunovirological response to combined antiretroviral therapy and drug resistance patterns in children: 1- and 2-year outcomes in rural Uganda

DOI: 10.1186/1471-2431-11-67

Keywords: Children, antiretroviral therapy, Uganda, rural population, patient compliance, drug resistance, pharmacokinetics

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Abstract:

Cross-sectional assessment of all children treated with ART for 12 (M12) and 24 (M24) months was performed. CD4 counts, HIV RNA levels, antiretroviral resistance patterns, and non-nucleoside reverse transcriptase inhibitor (NNRTI) plasma concentrations were determined. Patient adherence and antiretroviral-related toxicity were assessed.Cohort probabilities of retention in care were 0.86 at both M12 and M24. At survey, 71 (83%, M12) and 32 (78%, M24) children remained on therapy, and 84% participated in the survey. At ART start, 39 (45%) were female; median age was 5 years. Median initial CD4 percent was 11% [IQR 9-15] in children < 5 years old (n = 12); CD4 count was 151 cells/mm3 [IQR 38-188] in those ≥ 5 years old (n = 26). At M12, median CD4 gains were 11% [IQR 10-14] in patients < 5 years old, and 206 cells/mm3 [IQR 98-348] in ≥ 5 years old. At M24, median CD4 gains were 11% [IQR 5-17] and 132 cells/mm3 [IQR 87-443], respectively. Viral suppression (< 400 copies/mL) was achieved in 59% (M12) and 33% (M24) of children. Antiretroviral resistance was found in 25% (M12) and 62% (M24) of children. Overall, 29% of patients had subtherapeutic NNRTI plasma concentrations.After one year of therapy, satisfactory survival and immunological responses were observed, but nearly 1 in 4 children developed viral resistance and/or subtherapeutic plasma antiretroviral drug levels. Regular weight-adjustment dosing and strategies to reinforce and maintain ART adherence are essential to maximize duration of first-line therapy in children in resource-limited countries.Despite the progress made in the last few years, in 2009 only 356,400 of the estimated 2.5 million children currently infected with HIV were receiving combined antiretroviral therapy (ART) in low- and middle-income countries [1]. Ninety percent of children infected with HIV were living in sub-Saharan Africa and the ART coverage in this area was 26% [2]. In the absence of therapy, more than 50% of HIV-infected children di

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