van Dyk, Jennie, Waitt, Catriona 
ORCID: 0000-0003-0134-5855, Mugerwa, Henry, Wiesner, Lubbe, Orrell, Catherine, Bamford, Alasdair, Gibb, Diana M, McIlleron, Helen M, Colbers, Angela, Burger, David M et al (show 2 more authors)
(2026)
Population pharmacokinetics of ritonavir-boosted atazanavir in subsequent-line treatment in African children with HIV
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 70 (8).
e0059226-.
ISSN 0066-4804, 1098-6596
Abstract
Ritonavir-boosted atazanavir (atazanavir/r) is an effective once-daily option for pediatric subsequent-line antiretroviral therapy when used with two nucleoside reverse transcriptase inhibitors (NRTIs). Tuberculosis co-treatment complicates its use because rifampicin markedly induces atazanavir/r clearance. Although twice-daily atazanavir/r can overcome this interaction in adults, data in children are lacking. We aimed to characterize atazanavir population pharmacokinetics in children with HIV and simulate the effect of rifampicin co-treatment. Atazanavir concentration-time data in African children with HIV from CHAPAS-4 (ISRCTN22964075) and VirTUAL (NCT03923231) were analyzed by nonlinear mixed-effect modeling. We investigated the effect of weight, age, atazanavir formulation, ritonavir dose, and NRTI backbone (tenofovir alafenamide [TAF]-emtricitabine, abacavir-lamivudine, or zidovudine-lamivudine). Simulations were performed across weight bands to evaluate atazanavir/r exposures under standard conditions and, using adult-derived induction effects, predict exposures and possible dosing regimens during rifampicin co-treatment. Seventy children were included, with a median (range) age of 10.9 (3.2–17.7) years and weight of 29 (15–85) kg. A two-compartment model with sequential zero- and first-order absorption best described atazanavir disposition. The estimated typical value of atazanavir clearance was 4.8 L/h for a 27-kg individual. Atazanavir pharmacokinetics in children were unaffected by the NRTI backbone. Once-daily atazanavir/r with current dosing guidelines achieved adequate exposures across weight bands. When simulating pharmacokinetics during rifampicin co-treatment, twice-daily atazanavir/r is expected to restore exposures to levels comparable to once-daily dosing without rifampicin. These findings provide a framework for future clinical evaluation in children with HIV and tuberculosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | antiretroviral therapy, pediatric, NONMEM, drug interactions |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Inst. Life Courses & Medical Sciences (T&R staff) Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Women's & Children's Health |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 20 Jul 2026 08:12 |
| Last Modified: | 16 Sep 2026 02:55 |
| DOI: | 10.1128/aac.00592-26 |
| Open Access URL: | https://journals.asm.org/doi/10.1128/aac.00592-26 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3199449 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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