Kengo, A 
ORCID: 0009-0000-5084-4314, Resendiz-Galvan, JE, Najjemba, L ORCID: 0000-0002-2264-8292, Mugerwa, H, De Nicolò, A, D'Avolio, A ORCID: 0000-0002-1321-4126, Atoyebi, S ORCID: 0000-0002-1393-3753, Wiesner, L, Svensson, EM ORCID: 0000-0002-0093-6445, Waitt, C ORCID: 0000-0003-0134-5855 et al (show 1 more authors)
(2025)
Model-based evaluation of the interaction between ritonavir-boosted atazanavir and rifampicin in Ugandan adults with HIV
British Journal of Clinical Pharmacology, 91 (12).
pp. 3471-3481.
ISSN 0306-5251, 1365-2125
Abstract
Aim: Concomitant treatment of tuberculosis (TB) and human immunodeficiency virus (HIV) is complicated by drug-drug interactions (DDI). This analysis aimed to characterize the DDI between ritonavir-boosted atazanavir (ATV/r) and rifampicin in plasma and peripheral blood mononuclear cells (PBMC). Methods: The DERIVE study (NCT04121195) recruited Ugandan adults with HIV (not TB) on ATV/r-based second-line antiretroviral therapy, and collected intensive plasma and PBMC pharmacokinetic samples during four visits: (i) standard-dose ATV/r 300/100 mg QD, (ii) same ATV/r regimen adding rifampicin 600 mg QD, (iii) doubling ATV/r to BID with rifampicin 600 mg QD and (iv) ATV/r 300/100 mg BID with rifampicin increased to 1200 mg QD. ATV/r plasma and PBMC concentrations were analysed with population pharmacokinetic modelling in NONMEM. Results: Twenty-six participants (23 female) were enrolled, with median age and weight of 44 years and 67 kg, respectively. A two-compartment model with an effect-compartment effectively described atazanavir concentrations in plasma and PBMC. Rifampicin increased atazanavir clearance threefold, while decreasing its bioavailability and absorption rate. Doubling dosing frequency of ATV/r largely mitigated the interaction with rifampicin, restoring the proportion of simulated participants achieving the targeted trough atazanavir concentration of 0.014 mg/L to 99%. Rifampicin did not affect the ratio of atazanavir concentration between PBMCs and plasma. Conclusion: Metabolic induction by rifampicin accounts for the decrease in plasma exposure of ATV/r. Doubling the ATV/r dosing frequency to BID effectively mitigated this interaction. The plasma exposure of ATV/r mirrored that in PBMCs, suggesting that for these drugs, plasma concentrations provide a reliable reflection of site-of-action exposures.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | antiretrovirals, drug interactions, pharmacokinetics, pharmacometrics |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 15 Sep 2025 09:07 |
| Last Modified: | 28 Feb 2026 15:35 |
| DOI: | 10.1002/bcp.70195 |
| Open Access URL: | https://doi.org/10.1002/bcp.70195 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3194390 |
| 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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