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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*§

doi: 10.1097/FTD.0b013e3181cb479f
Original Article

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.

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.