Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial
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Date
2016
Journal Title
Journal ISSN
Volume Title
Publisher
The Lancet Infectious Diseases
Abstract
Background WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years.
No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral
therapy (ART) in Africa, where most HIV-infected children live. We aimed to compare stavudine, zidovudine, or
abacavir as dual or triple fi xed-dose-combination paediatric tablets with lamivudine and nevirapine or efavirenz.
Methods In this open-label, parallel-group, randomised trial (CHAPAS-3), we enrolled children from one centre in
Zambia and three in Uganda who were previously untreated (ART naive) or on stavudine for more than 2 years with
viral load less than 50 copies per mL (ART experienced). Computer-generated randomisation tables were incorporated
securely within the database. The primary endpoint was grade 2–4 clinical or grade 3/4 laboratory adverse events.
Analysis was intention to treat. This trial is registered with the ISRCTN Registry number, 69078957.
Findings Between Nov 8, 2010, and Dec 28, 2011, 480 children were randomised: 156 to stavudine, 159 to zidovudine,
and 165 to abacavir. After two were excluded due to randomisation error, 156 children were analysed in the stavudine
group, 158 in the zidovudine group, and 164 in the abacavir group, and followed for median 2·3 years (5% lost to
follow-up). 365 (76%) were ART naive (median age 2·6 years vs 6·2 years in ART experienced). 917 grade 2–4 clinical
or grade 3/4 laboratory adverse events (835 clinical [634 grade 2]; 40 laboratory) occurred in 104 (67%) children on
stavudine, 103 (65%) on zidovudine, and 105 (64%), on abacavir (p=0·63; zidovudine vs stavudine: hazard ratio [HR]
0·99 [95% CI 0·75–1·29]; abacavir vs stavudine: HR 0·88 [0·67–1·15]). At 48 weeks, 98 (85%), 81 (80%) and 95 (81%)
ART-naive children in the stavudine, zidovudine, and abacavir groups, respectively, had viral load less than 400 copies
per mL (p=0·58); most ART-experienced children maintained suppression (p=1·00). Interpretation All NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profi le and oncedaily dosing favours abacavir for African children, supporting WHO 2013 guidelines.
Description
Keywords
paediatric tablets, zidovudine, HIV, infected children
Citation
Mulenga, V., Musiime, V., Kekitiinwa, A., Cook, A. D., Abongomera, G., Kenny, J., ... & CHAPAS-3 Trial Team. (2016). Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. The Lancet Infectious Diseases, 16(2), 169-179.