CHAPAS 3: A randomised trial comparing stavudine vs zidovudine vs abacavir as NRTI backbone in NNRTI-based first-line ART in 478 HIV-infected children in Uganda and Zambia Victor Musiime 1 , Veronica Mulenga 2 , Adeodata Kekitiinwa 3 , Adrian Cook 4 , George Abongomera 5 , Margaret J.Thomason 4 , Grace Mirembe 1 , Violet Korutaro 3 , Chisala Chabala 2 , Julia Kenny 4 , Alice R. Asiimwe 3 , James Abach 5 , Chifumbe Chintu 2 , Cissy Kityo 1 , A. Sarah Walker 4 , Diana M.Gibb 4 , on behalf of the CHAPAS-3 trial team 1 Joint Clinical Research Centre, Kampala, Uganda, 2 University Teaching Hospital, Lusaka,Zambia; 3 Baylor-Uganda, Paediatric Infectious Diseases Clinic, Mulago Hospital, Kampala, Uganda; 4 Medical Research Council Clinical Trials Unit at UCL, London, UK; 5 Joint Clinical Research Centre, Gulu, Uganda
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CHAPAS 3: A randomised trial comparing stavudine
vs zidovudine vs abacavir as NRTI backbone in NNRTI-based first-line ART in 478 HIV-infected
children in Uganda and Zambia
Victor Musiime1, Veronica Mulenga2, Adeodata Kekitiinwa3, Adrian Cook4, George Abongomera5, Margaret J.Thomason4, Grace Mirembe1, Violet Korutaro3, Chisala
Chabala2, Julia Kenny4, Alice R. Asiimwe3, James Abach5, Chifumbe Chintu2, Cissy Kityo1, A. Sarah Walker4, Diana M.Gibb4, on behalf of the CHAPAS-3 trial team
1Joint Clinical Research Centre, Kampala, Uganda, 2University Teaching Hospital, Lusaka,Zambia; 3Baylor-Uganda, Paediatric Infectious Diseases Clinic, Mulago Hospital, Kampala, Uganda;
4Medical Research Council Clinical Trials Unit at UCL, London, UK; 5Joint Clinical Research Centre, Gulu, Uganda
Which Nucleoside Reverse Transcriptase Inhibitor (NRTI) in dispersible Fixed Dose Combination (FDC) ‘baby pills’?
• Lipodystrophy is well-documented in adults & adolescents on stavudine (d4T) – few data in younger children receiving lower WHO-
recommended doses in FDC dispersible pills • Alternative NRTIs include:
– Abacavir (ABC), but its efficacy has been questioned in cohort studies
– Zidovudine (ZDV) which may cause anaemia, particularly in malnourished children in endemic malaria areas
• No randomised trials comparing d4T, ZDV, ABC
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FDC baby pills with NNRTI and NRTIs
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CHAPAS 3 Trial Design 44
Age 1 month to 13 years Naïve – no previous ART and ready to start OR Experienced - 2yrs+ d4T with VL<50 copies/ml
d4T + 3TC/NNRTI ZDV + 3TC/NNRTI ABC + 3TC/NNRTI
minimum 96 weeks follow-up
Clinical grade 2/3/4 adverse event OR Laboratory adverse event, confirmed grade 3 or any grade 4
Conclusions • Young naïve children did very well on d4T, ZDV or ABC
based triple ART given as WHO-recommended FDCs – Low toxicity
• including anaemia, which appears mainly HIV-related • Including any signs of lipodystrophy
– High VL suppression; including with ABC • Experienced children previously on d4T did well on all arms:
– Lipodystrophy was rare – suppressed viral load was maintained
• Priority should be to identify children early and start ART, whichever NRTI is available • d4T could be used in younger children
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Members of the CHAPAS 3 trial team:
• University Teaching Hospital, Lusaka, Zambia: Veronica Mulenga, Chifumbe Chintu, Chishala Chabala, Desire Kabamba, Musaku Mwenechanya, Monica Kapasa, Carol Chijoka, Joyce Lungu, Semy Zulu, Terence Chipoya, Elias Chambela
• Joint Clinical research Centre, Kampala, Uganda:
Cissy Kityo, Victor Musiime, Grace Mirembe, Elizabeth Kaudha, Amos Drasiku, Bernard Bainomuhwezi, Priscilla Wavamunno, Florence Odongo, Winnie Namala, Daniel Sseremba, Alison Balaba, Alice Kwaga, Joshua Kayiwa, Matthew Odera, Paul Oronon, Edith Bagurukira, Phyllis Mwesigwa, Philip Apugulu
• Joint Clinical Research Centre, Gulu, Uganda:
George Abongomera, James Abach, Willy Odong, Beatrice Arach • Baylor-Uganda, PIDC, Mulago Hospital, Uganda:
Adeodata Kekitiinwa, Alice Asiimwe, Vincent Tukei, Violet Korutaro, Justine Komunyena, Carol Nansubuga, Muzamil Kisekka, Justine Mpanga
• Medical Research Council, Clinical Trials Unit, London, UK: Diana Gibb, Sarah Walker, Margaret Thomason, Adrian Cook, Julia Kenny, Ellen Owen-Powell, Charlotte Male, Adam Glabay
• Institute of Child Health, University College London, UK: Nigel Klein, Julia Kenny
• Radboud University, Nijmegen, Netherlands:
David Burger, Quirine Fillekes • University of Cape Town, Republic of South Africa: