Second-line tenofovir alafenamide for children with HIV in Africa
| dc.contributor.author | Musiime, V. | |
| dc.contributor.author | Musiime, V., Szubert, A.J. | |
| dc.contributor.author | Mujuru, H.A. | |
| dc.contributor.author | Kityo, C. | |
| dc.contributor.author | Doerholt, K. | |
| dc.contributor.author | Makumbi, S. | |
| dc.contributor.author | Mulenga, V. | |
| dc.contributor.author | Ndebele, W. | |
| dc.contributor.author | Mwamabazi, M. | |
| dc.contributor.author | McIlleron, H. | |
| dc.contributor.author | Bwakura-Dangarembizi, M. | |
| dc.date.accessioned | 2025-06-25T10:35:20Z | |
| dc.date.available | 2025-06-25T10:35:20Z | |
| dc.date.issued | 2024-04-21 | |
| dc.description.abstract | Background Children living with HIV have few second-line antiretroviral therapy(ART) options, especially fixed-dose-combinations(FDC). Methods Children from Uganda, Zambia, Zimbabwe were randomised to second-line tenofovir alafenamide(TAF)/emtricitabine(FTC) or standard-of-care(SOC) backbone (abacavir(ABC) or zidovudine(ZDV) with lamivudine(3TC)) in the factorial CHAPAS-4 trial. The second randomisation (reported elsewhere) was to dolutegravir(DTG), ritonavir-boosted darunavir(DRV/r), atazanavir(ATV/r) or lopinavir(LPV/r) as anchor drug. All drugs were dosed using WHO weight-bands and children <25kg received a new paediatric TAF/FTC(15/120mg) FDC tablet. The primary endpoint was viral load(VL)<400copies/ml at week-96, analysed using logistic regression, hypothesising that TAF/FTC would be non-inferior to SOC (10% margin). Secondary endpoints included safety and immunological outcomes. Analyses were intention-to-treat. Results 919 children 3–15years, 497(54%) male, median[IQR] baseline viral load(VL) 17,573copies/ml [5549-55,700] and CD4 count 669cells/mm3[413-971], spent 99% of time on allocated NRTI backbone. At week-96, 406/454(89.4%) receiving TAF/FTC vs. 378/454(83.3%) receiving SOC had VL<400copies/mL (adjusted difference[95%CI]: 6.3%[2.0%,10.6%], p=0.004), with no evidence that this varied by ABC/3TC or ZDV/3TC SOC. CD4 count improved similarly in both arms. Growth was better with TAF/FTC vs. SOC, without evidence of excess weight-gain with any backbone/anchor drug combination (including DTG±TAF/FTC, interaction p=0.51). Bone health parameters were similar between arms, irrespective of anchor drug. One child died (treatment-unrelated); 29(3%) had serious adverse events without differences between arms. Conclusions TAF/FTC was virologically superior to SOC ZDV/3TC or ABC/3TC with a favourable safety profile, irrespective of anchor drug. Development of child-friendly TAF/FTC FDCs (±anchor drug) would increase cost-effective ART options for children and reduce drug access gaps between children and adults.(ISRCTN22964075) | |
| dc.identifier.citation | Musiime, V., Szubert, A.J., Mujuru, H.A., Kityo, C., Doerholt, K., Makumbi, S., Mulenga, V., Ndebele, W., Mwamabazi, M., McIlleron, H. and Bwakura-Dangarembizi, M., 2024. Second-line tenofovir alafenamide for children with HIV in Africa. medRxiv, pp.2024-04. | |
| dc.identifier.uri | http://196.220.97.103:4000/handle/123456789/859 | |
| dc.language.iso | en | |
| dc.publisher | medRxiv | |
| dc.title | Second-line tenofovir alafenamide for children with HIV in Africa | |
| dc.type | Article |