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Abstracts of Oral Presentations
OA-225 Optimising second line anchor drug options for children with HIV in Africa: 96 week results of the CHAPAS-4 randomised trial
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  1. Abbas Lugemwa1,
  2. Alexander J Szubert2,
  3. Wedu Ndebele3,
  4. Sarah Walker2,
  5. Anna Turkova2,
  6. Sue Tafeni4,
  7. Grace Siziba3,
  8. Clare Shakeshaft2,
  9. Bwendo Nduna5,
  10. Rashida Nazzinda6,
  11. Esether Nambi6,
  12. Mwate Mwamabazi5,
  13. Godfrey Musoro4,
  14. Victor Musiime6,
  15. Veronica Mulenga7,
  16. Hilda Mujuru4,
  17. Helen McIlleron8,
  18. Shafic Makumbi1,
  19. Joyce Lungu7,
  20. Cissy Kityo6,
  21. Nimisha Dudakia2,
  22. Katja Doerholt2,
  23. Chishala Chabala7,
  24. Mutsa Bwakura-Dangarembizi4,
  25. Alasdair Bamford2,
  26. Diana M Gibb2,
  27. on behalf of the CHAPAS-4 clinical trial team
  1. 1Joint Clinical Research Centre, Uganda
  2. 2MRC Clinical Trials Unit at UCL, UK
  3. 3Mpilo Central Hospital, Zimbabwe
  4. 4University of Zimbabwe Clinical Research Centre, Zimbabwe
  5. 5Arthur Davison Children’s Hospital, Zambia
  6. 6Joint Clinical Research Centre, Uganda
  7. 7University Teaching Hospital, Zambia
  8. 8University of Cape Town, South Africa

Abstract

Background Paediatric second line antiretroviral therapy (ART) formulations are limited. CHAPAS-4 (ISRCTN22964075), a 2X4 factorial randomised trial investigated efficacy and safety of 4 anchor drugs.

Methods Children 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.

Results 919 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.

Conclusion These 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.

https://doi.org/10.1136/bmjgh-2023-EDC.18

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