Rilpivirine (RPV) has become a recommended non-nucleoside reverse transcriptase inhibitor (NNRTI), replacing efavirenz (EFV) due to fewer CNS effects. RPV pharmacokinetics (PK) data are limited among HIV-infected adolescents, particularly after switching from EFV, which potentially reduces rilpivirine exposure due to fading CYP3A inducing capacity. This study aims to describe the pharmacokinetic profile of RPV after switching from EFV in HIV-infected adolescents.
HIV-infected adolescents aged 12-18 years, weighing ≥ 25 kilograms, treated with EFV-based antiretroviral therapy for ≥ 3 months and HIV RNA (VL) < 50 copies/mL were switched from EFV to RPV. RPV 25 mg was taken once daily with a meal. At week 4, a PK profile was determined at 0 (pre-dose), 1, 2, 4, 5, 6, 9, 12 and 24 hours following an observed intake of RPV with a standardized meal (525 kcal). RPV concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS) method (lower limit of quantification (LLQ) 4 ng/mL). RPV PK parameters were calculated using a non-compartmental method (Winnonlin 6.3) and compared with published data (the PAINT and pooled ECHO/THRIVE PK substudies). The target RPV C24h was > 40 ng/mL. EFV plasma concentrations were measured at weeks 0 and 4 (LLQ 100 ng/mL). VL was measured at weeks 12 and 24. Adherence was determined by pill count.
From January to June 2016, 20 adolescents were enrolled; 12 adolescents were male. Median age and weight (range) were 15.7 years (13.8-18.9) and 49 kilograms (31-93) respectively. Median baseline CD4 count (range) was 726 cells/mm3 (236 – 1145). Pre-switching regimens were TDF/3TC/EFV (90%) and AZT/3TC/EFV (10%). 16 adolescents had adherence of > 95% at their PK visit. The PK parameters of RPV are shown in Table 1. All values from the present study are comparable with the PAINT and ECHO/THRIVE sub-studies. Four adolescents (20%) had RPV C24h < 40 ng/mL, of which two reported poor adherence < 95%. Mean (SD) EFV plasma concentrations at week 0 was 2030 ng/ml (1037) which median (range) post-dose were 14 hours (2-16), but none had detectable levels at week 4. All evaluable adolescents had undetectable VLs (< 50 copies/ml) at weeks 12 and 24.
HIV-infected adolescents switching from EFV to RPV had adequate RPV pharmacokinetic profiles and there was no virological failure detected at 24 weeks following switching.