Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response: A sub-study of the NEAT001/ANRS143 randomized trial
| Title: | Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response: A sub-study of the NEAT001/ANRS143 randomized trial |
|---|---|
| Authors: | Dickinson L.; Gurjar R.; Stohr W.; Bonora S.; Owen A.; D'Avolio A.; Cursley A.; Molina J. -M.; Faetkenheuer G.; Vandekerckhove L.; Di Perri G.; Pozniak A.; Richert L.; Raffi F.; Boffito M.; Dedes N.; Chene G.; Allavena C.; Autran B.; Antinori A.; Bucciardini R.; Vella S.; Horban A.; Arribas J.; Babiker A. G.; Pillay D.; Franquet X.; Schwarze S.; Grarup J.; Fischer A.; Wallet C.; Diallo A.; Saillard J.; Moecklinghoff C.; Stellbrink H. -J.; Vanleeuwen R.; Gatell J.; Sandstrom E.; Flepp M.; Ewings F.; George E. C.; Hudson F.; Pearce G.; Quercia R.; Rogatto F.; Leavitt R.; Nguyen B. -Y.; Peto T.; Goebel F.; Marcotullio S.; Miller V.; Sasieni P.; Arnault F.; Boucherie C.; Jean D.; Paniego V.; Paraina F.; Rouch E.; Schwimmer C.; Soussi M.; Taieb A.; Termote M.; Touzeau G.; Babiker A.; Dodds W.; Hoppe A.; Kummeling I.; Pacciarini F.; Paton N.; Russell C.; Taylor K.; Ward D.; Aagaard B.; Eid M.; Gey D.; Gramjensen B.; Jakobsen M. -L.; Jansson P. O.; Jensen K.; Mariajoensen Z.; Moseholmlarsen E.; Pahl C.; Pearson M.; Nielsen B. R.; Reilev So. S.; Christ I.; Lathouwers D.; Manting C.; Van Leeuwen R.; Mendy B.; Metro A.; Couffin-Cadiergues S.; Knellwolf A. -L.; Palmisiano L.; Aznar E.; Barea C.; Cotarelo M.; Esteban H.; Girbau I.; Moyano B.; Ramirez M.; Saiz C.; Sanchez I.; Yllescas M.; Binelli A.; Colasanti V.; Massella M.; Anagnostou O.; Gioukari V.; Touloumi G.; Schmied B.; Rieger A.; Vetter N.; Dewit S.; Florence E.; Gerstoft J.; Mathiesen L.; Katlama C.; Cabie A.; Cheret A.; Dupon M.; Ghosn J.; Girard P. -M.; Goujard C.; Levy Y.; Morlat P.; Neau D.; Obadia M.; Perre P.; Piroth L.; Reynes J.; Tattevin P.; Ragnaud J. M.; Weiss L.; Yazdan Y.; Yeni P.; Zucman D.; Esser S.; Fatkenheuer G.; Hoffmann C.; Jessen H.; Rockstroh J.; Schmidt R.; Stephan C.; Unger S.; Hatzakis A.; Daikos G. L.; Papadopoulos A.; Skoutelis A.; Banhegyi D.; Mallon P.; Mulcahy F.; Andreoni M.; Castelli F.; D'Arminiomonforte A.; Diperri G.; Galli M.; Lazzarin A.; Mazzotta F.; Torti C.; Vullo V.; Prins J.; Richter C.; Verhagen D.; Vaneeden A.; Doroana M.; Antunes F.; Maltez F.; Sarmento-Castro R.; Gonzalez Garcia J.; Aldeguer J. L.; Clotet B.; Domingo P.; Gatell J. M.; Knobel H.; Marquez M.; Pilarmiralles M.; Portilla J.; Soriano V.; Tellez M.; Thalme A.; Blaxhult A.; Gisslen M.; Winston A.; Fox J.; Gompels M.; Herieka E.; Johnson M.; Leen C.; Teague A.; Williams I.; Boyd M.; Moller N. F.; Moseholmlarsen E. F.; Lemoing V.; Wit F. W. N. M.; Kowalska J.; Berenguer J.; Moreno S.; Muller N. J.; Torok E.; Post F.; Angus B.; Calvez V.; Boucher C.; Collins S.; Dunn D.; Lambert S.; Marcelin A. -G.; Perno C. F.; White E.; Ammassari A.; Schmidt R. E.; Odermarsky M.; Smith C.; Thiebaut R.; Delaserna J. I. B.; Castagna A.; De Wit S.; Furrer H. -J.; Mocroft A.; Reiss P.; Fragola V.; Lauriola M.; Murri R.; Nieuwkerk P.; Spire B.; Volny-Anne A.; West B.; Amieva H.; Llibre Codina J.; Braggion M.; Foca E. |
| Contributors: | Dickinson, L.; Gurjar, R.; Stohr, W.; Bonora, S.; Owen, A.; D'Avolio, A.; Cursley, A.; Molina, J. -M.; Faetkenheuer, G.; Vandekerckhove, L.; Di Perri, G.; Pozniak, A.; Richert, L.; Raffi, F.; Boffito, M.; Dedes, N.; Chene, G.; Allavena, C.; Autran, B.; Antinori, A.; Bucciardini, R.; Vella, S.; Horban, A.; Arribas, J.; Babiker, A. G.; Pillay, D.; Franquet, X.; Schwarze, S.; Grarup, J.; Fischer, A.; Wallet, C.; Diallo, A.; Saillard, J.; Moecklinghoff, C.; Stellbrink, H. -J.; Vanleeuwen, R.; Gatell, J.; Sandstrom, E.; Flepp, M.; Ewings, F.; George, E. C.; Hudson, F.; Pearce, G.; Quercia, R.; Rogatto, F.; Leavitt, R.; Nguyen, B. -Y.; Peto, T.; Goebel, F.; Marcotullio, S.; Miller, V.; Sasieni, P.; Arnault, F.; Boucherie, C.; Jean, D.; Paniego, V.; Paraina, F.; Rouch, E.; Schwimmer, C.; Soussi, M.; Taieb, A.; Termote, M.; Touzeau, G.; Babiker, A.; Dodds, W.; Hoppe, A.; Kummeling, I.; Pacciarini, F.; Paton, N.; Russell, C.; Taylor, K.; Ward, D.; Aagaard, B.; Eid, M.; Gey, D.; Gramjensen, B.; Jakobsen, M. -L.; Jansson, P. O.; Jensen, K.; Mariajoensen, Z.; Moseholmlarsen, E.; Pahl, C.; Pearson, M.; Nielsen, B. R.; Reilev, So. S.; Christ, I.; Lathouwers, D.; Manting, C.; Van Leeuwen, R.; Mendy, B.; Metro, A.; Couffin-Cadiergues, S.; Knellwolf, A. -L.; Palmisiano, L.; Aznar, E.; Barea, C.; Cotarelo, M.; Esteban, H.; Girbau, I.; Moyano, B. |
| Publisher Information: | Oxford University Press |
| Publication Year: | 2020 |
| Description: | Objectives: NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. Methods: Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5∗3, CYP3A4∗22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0-24 and C24 with time to virological failure was evaluated by Cox regression. Results: Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000518550200020; volume:75; issue:3; firstpage:628; lastpage:639; numberofpages:12; journal:JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY; https://hdl.handle.net/20.500.11768/107460 |
| DOI: | 10.1093/jac/dkz479 |
| Availability: | https://hdl.handle.net/20.500.11768/107460; https://doi.org/10.1093/jac/dkz479 |
| Accession Number: | edsbas.F72E2BD2 |
| Database: | BASE |