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

BMC Pediatrics

Mar Pujades-Rodríguez³  Charles Olaro⁷  David M Olson⁶  Suna Balkan¹  Anne-Marie Taburet²  Paul Anguzu⁴  Loretxu Pinoges³  Christine Rouzioux⁵  Gunar Guenther³  Laurence Ahoua³ 

[1]Medical Department, Médecins Sans Frontières, Paris, France

[2]Laboratory of Clinical Pharmacology, Bicêtre Hospital, Kremlin Bicêtre, France

[3]Clinical Research Department, Epicentre, Paris, France

[4]Department of Operations, Médecins Sans Frontières, Arua, Uganda

[5]Laboratory of Virology, Necker Hospital, Paris, France

[6]Medical Department, Médecins Sans Frontières, New York, USA

[7]Medical and Administrative Hospital Direction, Arua Regional Referral Hospital, Arua, Uganda

关键词: pharmacokinetics;    drug resistance;    patient compliance;    rural population;    Uganda;    antiretroviral therapy;    Children;   

Others  :  1172142
DOI  :  10.1186/1471-2431-11-67

 received in 2011-05-09, accepted in 2011-07-26,  发布年份 2011

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2011 Ahoua et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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