OA-225 Optimising second line anchor drug options for children with HIV in Africa: 96 week results of the CHAPAS-4 randomised trial

BackgroundPaediatric second line antiretroviral therapy (ART) formulations are limited. CHAPAS-4 (ISRCTN22964075), a 2X4 factorial randomised trial investigated efficacy and safety of 4 anchor drugs. MethodsChildren from Uganda, Zambia and Zimbabwe on non-nucleoside reverse transcriptase inhibitor-b...

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Published in:	BMJ global health Vol. 8; no. Suppl 10; p. A8
Main Authors:	Lugemwa, Abbas, Szubert, Alexander J, Ndebele, Wedu, Walker, Sarah, Turkova, Anna, Tafeni, Sue, Siziba, Grace, Shakeshaft, Clare, Nduna, Bwendo, Nazzinda, Rashida, Nambi, Esether, Mwamabazi, Mwate, Musoro, Godfrey, Musiime, Victor, Mulenga, Veronica, Mujuru, Hilda, McIlleron, Helen, Makumbi, Shafic, Lungu, Joyce, Kityo, Cissy, Dudakia, Nimisha, Doerholt, Katja, Chabala, Chishala, Bwakura-Dangarembizi, Mutsa, Bamford, Alasdair, Gibb, Diana M
Format:	Journal Article
Language:	English
Published:	London BMJ Publishing Group Ltd 17-12-2023 BMJ Publishing Group LTD
Subjects:	Abstracts of Oral Presentations Antiretroviral drugs Clinical trials HIV Human immunodeficiency virus Medical research Pediatrics Africa
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Summary:	BackgroundPaediatric second line antiretroviral therapy (ART) formulations are limited. CHAPAS-4 (ISRCTN22964075), a 2X4 factorial randomised trial investigated efficacy and safety of 4 anchor drugs. MethodsChildren from Uganda, Zambia and Zimbabwe on non-nucleoside reverse transcriptase inhibitor-based regimens, requiring second line ART, were randomised to dolutegravir (DTG) or ritonavir-boosted darunavir(DRV/r), atazanavir(ATV/r) or lopinavir(LPV/r) dosed according to WHO weight-bands. Primary endpoint was week-96 viral load(VL)<400copies/mL. We hypothesised ATV/r would be non-inferior to LPV/r(12% margin); both DRV/r and DTG superior to LPV/r and ATV/r arms combined (superiority threshold p≤0.03; multiple comparisons). Analysis was intention-to-treat, based on logistic regression. Results of second randomisation (tenofovir alafenamide(TAF)-based vs. SOC backbone) will be reported separately. Results919 children aged 3–15years (54%male, median[IQR] viral load 17,573copies/mL[5549, 55,700]; CD4 count 669[413, 971]) were randomised and spent 98% of time on allocated regimen. At week-96 208/226(92.0%) on DTG, 203/230(88.3%) on DRV/r, 193/229(84.3%) on ATV/r, 180/223(80.7%) on LPV/r had VL<400c/ml. DTG was superior to LPV/r and ATV/r (adjusted difference 9.7%[4.8, 14.5],p<0.0001); DRV/r showed a trend to superiority to LPV/r and ATV/r (5.6%[0.3, 11.0],p=0.04); ATV/r was non-inferior to LPV/r (3.4%[-3.4, 10.2],p=0.33). Results were similar for VL<60copies/mL and <1000copies/mL and at weeks 48 and 144. CD4 count improved in all arms. More grade 3/4 adverse events(AE), predominantly hyperbilirubinemia, occurred for ATV/r vs LPV/r(p<0.0001); DTG had fewer AE vs. LPV/r(p=0.02). There was no evidence of excess weight-gain. Improvement in growth parameters were lowest with LPV/r. Renal and bone health was similar between arms. One child died (treatment-unrelated); 3% had serious adverse events.ConclusionThese results supports current WHO guidelines for preferred and alternative second line ART. In the future children will require second line ART after first line DTG. Ongoing development of child-friendly boosted DRV and ATV will be key to ensure robust treatment options are available for children in Africa.
Bibliography:	Abstracts of The Eleventh EDCTP Forum, 7–10 November 2023
ISSN:	2059-7908
DOI:	10.1136/bmjgh-2023-EDC.18