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Seventy\u2010four participants receiving either atazanavir\/ritonavir (ATV\/RTV) or efavirenz (EFV) with tenofovir\/emtricitabine (TFV\/FTC) provided PK and PGx information. Aging\u2010PGx\u2010PK association and interaction analyses were conducted using one\u2010way analysis of variance (ANOVA), multiple linear regression, and Random Forest ensemble methods. Our analyses associated unbound ATV disposition with multidrug resistance protein (MRP)4, RTV with P\u2010glycoprotein (P\u2010gp), and EFV with cytochrome P450 (CYP)2B6 and MRP4 genetic variants. The clearance and cellular distribution of TFV were associated with P\u2010gp, MRP2, and concentrative nucleoside transporters (CNTs), and FTC parameters were associated with organic cation transporters (OCTs) and MRP2 genetic variants. Notably, p16<jats:sup>INK4a<\/jats:sup> expression, a cellular aging marker, predicted EFV and FTC PK when genetic factors were adjusted. Both age and p16<jats:sup>INK4a<\/jats:sup> expression interacted with PGx on ATV and TFV disposition, implying potential dose adjustment based on aging may depend on genetic background.<\/jats:p>","DOI":"10.1111\/cts.12525","type":"journal-article","created":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T10:19:45Z","timestamp":1512469185000},"page":"226-236","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacogenetic Analysis of the Model\u2010Based Pharmacokinetics of Five Anti\u2010HIV Drugs: How Does This Influence the Effect of Aging?"],"prefix":"10.1111","volume":"11","author":[{"given":"Jingxian","family":"Chen","sequence":"first","affiliation":[{"name":"University of North Carolina Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farida S.","family":"Akhtari","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences North Carolina State University  Raleigh NC USA"},{"name":"Bioinformatics Research Center North Carolina State University  Raleigh NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Wagner","sequence":"additional","affiliation":[{"name":"University of North Carolina Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Suzuki","sequence":"additional","affiliation":[{"name":"University of North Carolina Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Wiltshire","sequence":"additional","affiliation":[{"name":"University of North Carolina Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison A.","family":"Motsinger\u2010Reif","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Center North Carolina State University  Raleigh NC USA"},{"name":"Department of Statistics North Carolina State University  Raleigh NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie B.","family":"Dumond","sequence":"additional","affiliation":[{"name":"University of North Carolina Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,3]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0456-6"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.12.138"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-016-1381-x"},{"key":"e_1_2_9_4_1","unstructured":"UNAIDS Report. 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