Pharmacokinetics of rilpivirine and 24-week outcomes after switching from efavirenz in virologically suppressed HIV-1-infected adolescents

Antivir Ther. 2018;23(3):259-265. doi: 10.3851/IMP3198.

Abstract

Background: Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor drug, could be a favourable drug for maintenance therapy in HIV-infected adolescents because it has few long-term side effects. However, data among adolescents switching from efavirenz (EFV) to RPV are limited. This study investigated the pharmacokinetics (PK), safety and efficacy of RPV in virologically suppressed HIV-1-infected adolescents after switching from EFV.

Methods: Adolescents aged 12-18 years on EFV-based antiretroviral therapy (ART) were switched from EFV to RPV (25 mg, once daily). Intensive 24-h blood samplings at 0 (pre-dose), 1, 2, 4, 5, 6, 9, 12 and 24 h were performed 4 weeks after switching. PK parameters were calculated using a non-compartmental method and compared with published data from the PAINT and pooled ECHO/THRIVE substudies. HIV RNA level was measured at weeks 12 and 24. Biochemical profiles were measured at baseline and week 24.

Results: From January to June 2016, 20 adolescents (12 male) were enrolled. Median (IQR) age was 16 (15-17) years and weight was 49 (42-59) kg. Mean (sd) AUC24 h, C24 h and Cmax of RPV were 2,041 (745) ng•h/ml, 69 (29) ng/ml and 143 (65) ng/ml, respectively. Median (IQR) Tmax was 5 (2-9) h. Four adolescents had C24 h <40 ng/ml. All PK parameters were comparable with published data. All adolescents remained virologically suppressed at week 24. Significant decreases in fasting total cholesterol, triglyceride and low-density lipoprotein were observed (P-value <0.05).

Conclusions: Virologically suppressed HIV-infected adolescents had adequate RPV exposure and remained virologically suppressed after switching from EFV. RPV can be used as long-term maintenance ART in HIV-infected adolescents.

Trial registration: ClinicalTrials.gov NCT03033368.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Benzoxazines / administration & dosage
  • Benzoxazines / pharmacokinetics
  • Benzoxazines / therapeutic use
  • Biomarkers
  • Drug Substitution
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • Humans
  • Male
  • Rilpivirine / administration & dosage
  • Rilpivirine / pharmacokinetics
  • Rilpivirine / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-HIV Agents
  • Benzoxazines
  • Biomarkers
  • Rilpivirine
  • efavirenz

Associated data

  • ClinicalTrials.gov/NCT03033368