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Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label,
Veronica Mulenga1, Victor Musiime2, Adeodata Kekitiinwa3
1Department of Paediatrics, University Teaching Hospital, Lusaka, Zambia.
Insights
In a trial of HIV-infected children in Africa, stavudine, zidovudine, and abacavir showed similar low toxicity and good treatment responses. Abacavir is favored for its dosing and resistance profile, supporting WHO guidelines.
Area of Science:
- Paediatric infectious diseases
- HIV/AIDS treatment
- Clinical pharmacology
Background:
- WHO 2013 guidelines advocate universal antiretroviral therapy (ART) for children under 5.
- Limited paediatric trials exist comparing nucleoside reverse-transcriptase inhibitors (NRTIs) for first-line ART in Africa.
- The CHAPAS-3 trial addresses this gap by comparing key NRTIs in African children.
Purpose of the Study:
- To compare the safety and efficacy of stavudine, zidovudine, and abacavir in first-line ART for HIV-infected children in Africa.
- To evaluate clinical and laboratory adverse events as the primary endpoint.
- To assess virological and immunological responses to different NRTI regimens.
Main Methods:
- An open-label, parallel-group, randomized trial (CHAPAS-3) involving ART-naive and ART-experienced children in Zambia and Uganda.
- 480 children were randomized to receive stavudine, zidovudine, or abacavir, combined with lamivudine and nevirapine or efavirenz.
- Primary endpoint: grade 2-4 clinical or grade 3/4 laboratory adverse events. Median follow-up was 2.3 years.
Main Results:
- No significant difference in grade 2-4 clinical or grade 3/4 laboratory adverse events among the three NRTI groups (p=0.63).
- High viral load suppression rates at 48 weeks in ART-naive children: 85% (stavudine), 80% (zidovudine), and 81% (abacavir).
- ART-experienced children largely maintained viral suppression.
Conclusions:
- All tested NRTIs demonstrated low toxicity and favorable clinical, immunological, and virological outcomes in African children.
- Lipodystrophy was not observed in children under 5; zidovudine did not increase anemia frequency.
- Abacavir is recommended due to its favorable resistance profile, once-daily dosing, and absence of hypersensitivity reactions, aligning with WHO 2013 guidelines.
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 fixed-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 profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines.
Funding:
European Developing Countries Clinical Trials Partnership.
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