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.

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).

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 EC_90.

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.