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Effect of Nevirapine on the Steady-State Trough Concentrations of Atazanavir in HIV-Infected Patients Receiving Atazanavir/Ritonavir

Moltó, José MD, PhD*; Deig, Elisabet MD†; Valle, Marta PharmD, PhD‡; Maria Llibre, Josep MD*; Miranda, Cristina BsCh*; Cedeño, Samandhy PhD§; Valero, Silvia MD‖; Negredo, Eugenia MD, PhD*; Clotet, Bonaventura MD, PhD*§

Therapeutic Drug Monitoring:
doi: 10.1097/FTD.0b013e3181cb479f
Original Article
Abstract

Material and Methods: To evaluate the influence of nevirapine on atazanavir trough concentrations (Ctrough) in a group of HIV-infected patients, we performed an open-label pilot study enrolling patients receiving 300/100 mg atazanavir/ritonavir once daily for 2 weeks or longer. Nevirapine was added at a dose of 200 mg once daily from Days 0 to 14 and 200 mg twice daily from Days 14 to 28. Atazanavir and nevirapine plasma Ctroughs were determined at Days 0 and 28. Atazanavir Ctroughs were compared between Days 0 and 28. Atazanavir and nevirapine Ctroughs at Day 28 were compared with historical controls receiving either 400 mg atazanavir once daily or 200 mg nevirapine twice daily.

Results: Fourteen patients were enrolled and 11 completed the study. The geometric mean (range) atazanavir Ctrough decreased from 0.631 mg/L (range, 0.235-1.87 mg/L) at Day 0 to 0.316 mg/L (range, 0.142-1.109 mg/L) at Day 28 to give a geometric mean ratio of 0.59 (95% confidence interval, 0.38-0.80; P = 0.026); nonetheless, the atazanavir Ctrough remained higher than the minimum effective concentration in 80% of the participants and higher than the median concentration in the control subjects receiving 400 mg atazanavir once daily without ritonavir (geometric mean ratio, 3.20; 95% confidence interval, 1.65-6.22; P = 0.001). The nevirapine Ctrough at Day 28 was slightly higher than in the historical controls on 200 mg nevirapine twice daily without atazanavir (geometric mean ratio, 1.46; 95% confidence interval, 1.04-2.06; P = 0.030).

Conclusion: We conclude that coadministration of 300/100 mg atazanavir/ritonavir once daily plus 200 mg nevirapine twice daily was safe and well tolerated but resulted in a decrease of atazanavir Ctrough by nearly half. Therefore, monitoring atazanavir Ctrough is recommended in patients treated with this drug combination, and increasing the atazanavir dose might be necessary.

Author Information

From the *“Lluita contra la Sida” Foundation, HIV Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; †Internal Medicine Department, Hospital General de Granollers, Granollers, Spain; ‡Centre d'Investigació del Medicament, Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; §IrsiCaixa” Foundation, HIV Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; and ‖Internal Medicine Department, Hospital Sant Jaume de Calella, Calella, Spain.

Received for publication July 31, 2009; accepted November 17, 2009.

This study was funded by a grant from the “Lluita contra la SIDA” Foundation and by ISCIII-RETIC RD06/006. The research leading to these results has also received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under the project “Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN),” grant agreement number 223131. M.V. is supported by FIS through grant CP04/00121 from the Spanish Health Department in collaboration with the “Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau,” Barcelona and is a member of CIBERSAM Network.

J.M. and E.D. contributed equally to this article.

Correspondence: José Moltó, MD, PhD, Fundació Lluita contra la SIDA, Hospital Universitari Germans Trias i Pujol, Ctra de Canyet, s/n. 08916 Badalona, Barcelona, Spain (e-mail: jmolto@flsida.org).

© 2010 Lippincott Williams & Wilkins, Inc.