Rilpivirine exposure in plasma and sanctuary site compartments after switching from nevirapine-containing combined antiretroviral therapy

• Published in: Journal of antimicrobial chemotherapy Vol. 69; no. 6; pp. 1642 - 1647
• Main Authors: Mora-Peris, Borja, Watson, Victoria, Vera, Jaime H., Weston, Rosy, Waldman, Adam D., Kaye, Steve, Khoo, Saye, Mackie, Nicola E., Back, David, Winston, Alan
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.06.2014; Oxford Publishing Limited (England)
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacokinetics; Antiretroviral drugs; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cerebrospinal Fluid - metabolism; Drug Substitution; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; Human immunodeficiency virus; Humans; Male; Middle Aged; Nevirapine - administration & dosage; Nevirapine - pharmacokinetics; Nitriles - administration & dosage; Nitriles - pharmacokinetics; Pharmacology; Plasma; Prescription drugs; Pyrimidines - administration & dosage; Pyrimidines - pharmacokinetics; Rilpivirine; Semen - metabolism; Switching; Viral Load; seminal plasma; nevirapine; CSF; switch
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dku018

Objectives Pharmacokinetic parameters following modifications to antiretroviral therapy and sanctuary site exposure are often unknown for recently licensed antiretrovirals. We assessed plasma, CSF and seminal plasma (SP) exposure of rilpivirine after switching from nevirapine. Methods HIV-infected male subjects receiving tenofovir/emtricitabine/nevirapine (245/200/400 mg) once daily switched to tenofovir/emtricitabine/rilpivirine (245/200/25 mg) once daily for 60 days when CSF and semen samples were collected. Mean and individual plasma concentrations of nevirapine and rilpivirine were compared with the proposed plasma target concentration for nevirapine (3000 ng/mL) and the protein binding-adjusted EC90 for rilpivirine (12.1 ng/mL). Mean rilpivirine CSF and SP concentrations were calculated and individual values compared with the EC50 and EC90 for wild-type virus (0.27 and 0.66 ng/mL, respectively). Results Of 13 subjects completing study procedures including CSF examination, 8 provided seminal samples. By day 3, the mean plasma rilpivirine trough concentration was 29.7 ng/mL (95% CI: 23.8–37). No patient presented rilpivirine plasma concentrations under the proposed threshold. The mean rilpivirine concentration in CSF was 0.8 ng/mL (95% CI: 0.7–1.0), representing a CSF : plasma ratio of 1.4%, with concentrations above the EC90 in 85% (11/13) of patients. In SP, the mean rilpivirine concentration was 4.9 ng/mL (95% CI: 3.3–7.2), representing an SP : plasma ratio of 9.5%, with all concentrations above the EC90. Conclusions Switching from nevirapine- to rilpivirine-containing antiretroviral therapy was safe and well tolerated, with plasma rilpivirine concentrations above the protein binding-adjusted EC90 in all subjects. Rilpivirine concentrations were always above the EC50 in the CSF and the EC90 in SP.