Musiime, Victor;
Bwakura-Dangarembizi, Mutsa;
Szubert, Alexander J;
Mumbiro, Vivian;
Mujuru, Hilda A;
Kityo, Cissy M;
Lugemwa, Abbas;
... CHAPAS-4 Trial Team; + view all
(2025)
Second-Line Antiretroviral Therapy for Children Living with HIV in Africa.
New England Journal of Medicine
, 392
(19)
pp. 1917-1932.
10.1056/NEJMoa2404597.
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Abstract
BACKGROUND: Children living with human immunodeficiency virus (HIV) have limited options for second-line antiretroviral therapy (ART). METHODS: In this open-label trial with a 2-by-4 factorial design, we randomly assigned children with HIV who had first-line treatment failure to receive second-line therapy with tenofovir alafenamide fumarate (TAF)-emtricitabine or standard care (abacavir or zidovudine, plus lamivudine) as the backbone and dolutegravir or ritonavir-boosted darunavir, atazanavir, or lopinavir as the anchor drug. The primary outcome was a viral load of less than 400 copies per milliliter at 96 weeks. We hypothesized that TAF-emtricitabine would be noninferior to standard care, that dolutegravir and ritonavir-boosted darunavir would each be superior to ritonavir-boosted lopinavir and atazanavir analyzed in combination, and that ritonavir-boosted atazanavir would be noninferior to ritonavir-boosted lopinavir. Safety was also assessed. RESULTS: A total of 919 children underwent randomization; 458 were assigned to receive TAF-emtricitabine, and 461 to receive standard care. Assigned anchor drugs were dolutegravir (229 participants), ritonavir-boosted darunavir (232), ritonavir-boosted atazanavir (231), and ritonavir-boosted lopinavir (227). The median age of participants was 10 years, and 497 (54.1%) were male. The median viral load at baseline was 17,573 copies per milliliter. At week 96, TAF-emtricitabine was superior to standard care: the adjusted difference in the percentage of participants with a viral load of less than 400 copies per milliliter was 6.3 percentage points (95% confidence interval [CI], 2.0 to 10.6; P = 0.004). Dolutegravir was superior to ritonavir-boosted lopinavir and atazanavir analyzed in combination (adjusted difference, 9.7 percentage points; 95% CI, 4.8 to 14.5; P<0.001), but ritonavir-boosted darunavir was not (adjusted difference, 5.6 percentage points; 95% CI, 0.3 to 11.0; P = 0.04 [prespecified threshold, P = 0.03]). Ritonavir-boosted atazanavir was noninferior to ritonavir-boosted lopinavir. One child died, and 29 (3.2%) had serious adverse events, with no significant between-group differences. CONCLUSIONS: Second-line ART regimens including TAF-emtricitabine and dolutegravir were effective for children, with no evidence of safety concerns. Ritonavir-boosted darunavir was also effective. (Funded by the European and Developing Countries Clinical Trials Partnership and others; CHAPAS-4 ISRCTN Registry number, ISRCTN22964075.).
| Type: | Article |
|---|---|
| Title: | Second-Line Antiretroviral Therapy for Children Living with HIV in Africa |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1056/NEJMoa2404597 |
| Publisher version: | https://doi.org/10.1056/nejmoa2404597 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Humans, HIV Infections, Male, Female, Child, Viral Load, Pyridones, Drug Therapy, Combination, Adolescent, Oxazines, Child, Preschool, Heterocyclic Compounds, 3-Ring, Piperazines, Anti-HIV Agents, Ritonavir, Lopinavir, Antiretroviral Therapy, Highly Active, Tenofovir, CD4 Lymphocyte Count, Emtricitabine |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10208722 |
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