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This analysis aimed to characterize the DDI between ritonavir\u2010boosted atazanavir (ATV\/r) and rifampicin in plasma and peripheral blood mononuclear cells (PBMC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The DERIVE study (NCT04121195) recruited Ugandan adults with HIV (not TB) on ATV\/r\u2010based second\u2010line antiretroviral therapy, and collected intensive plasma and PBMC pharmacokinetic samples during four visits: (i) standard\u2010dose ATV\/r 300\/100\u2009mg QD, (ii) same ATV\/r regimen adding rifampicin 600\u2009mg QD, (iii) doubling ATV\/r to BID with rifampicin 600\u2009mg QD and (iv) ATV\/r 300\/100\u2009mg BID with rifampicin increased to 1200\u2009mg QD. ATV\/r plasma and PBMC concentrations were analysed with population pharmacokinetic modelling in NONMEM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty\u2010six participants (23 female) were enrolled, with median age and weight of 44\u2009years and 67\u2009kg, respectively. A two\u2010compartment model with an effect\u2010compartment 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\u2009mg\/L to 99%. Rifampicin did not affect the ratio of atazanavir concentration between PBMCs and plasma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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\u2010of\u2010action exposures.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70195","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T23:18:03Z","timestamp":1755040683000},"page":"3471-3481","source":"Crossref","is-referenced-by-count":1,"title":["Model\u2010based evaluation of the interaction between ritonavir\u2010boosted atazanavir and rifampicin in Ugandan adults with HIV"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5084-4314","authenticated-orcid":false,"given":"Allan","family":"Kengo","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan 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