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

• Published in: BMC pediatrics Vol. 11; no. 1; p. 67
• Main Authors: Ahoua, Laurence, Guenther, Gunar, Rouzioux, Christine, Pinoges, Loretxu, Anguzu, Paul, Taburet, Anne-Marie, Balkan, Suna, Olson, David M, Olaro, Charles, Pujades-Rodríguez, Mar
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.07.2011; BioMed Central; BMC
• Subjects: Acquired immune deficiency syndrome; AIDS; Anti-Retroviral Agents - therapeutic use; Antiretroviral drugs; antiretroviral therapy; Antiviral agents; CD4 Lymphocyte Count; Child; Child, Preschool; Children; Cohort Studies; Cross-Sectional Studies; Diagnosis; Drug resistance; Drug Resistance, Viral; Drug therapy; Drug Therapy, Combination; Female; Follow-Up Studies; Health aspects; HIV; HIV infection; HIV Infections - drug therapy; HIV Infections - virology; Human immunodeficiency virus; Humans; Male; patient compliance; pharmacokinetics; Retrospective Studies; Reverse Transcriptase Inhibitors - blood; RNA, Viral - blood; Rural Population; Uganda; Uganda; France; United States
• ISSN: 1471-2431; 1471-2431
• DOI: 10.1186/1471-2431-11-67

Children living with HIV continue to be in urgent need of combined antiretroviral therapy (ART). Strategies to scale up and improve pediatric HIV care in resource-poor regions, especially in sub-Saharan Africa, require further research from these settings. We describe treatment outcomes in children treated in rural Uganda after 1 and 2 years of ART start. 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/mm(3) [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/mm(3) [IQR 98-348] in ≥ 5 years old. At M24, median CD4 gains were 11% [IQR 5-17] and 132 cells/mm(3) [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.