The DIANA Study: Continued Access to Darunavir/Ritonavir (DRV/r) and Long-Term Safety Follow-Up in HIV-1-Infected Pediatric Patients Aged 3 to < 18 Years

Drug Saf. 2021 Apr;44(4):439-446. doi: 10.1007/s40264-020-01032-0. Epub 2020 Dec 24.

Abstract

Introduction: Darunavir is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor boosted with ritonavir (DRV/r) or cobicistat.

Objective: This study provided continued access to DRV/r and assessed long-term safety in patients aged 3 to < 18 years.

Methods: Patients who had completed treatment in the DELPHI (TMC114-C212), DIONE (TMC114-TiDP29-C230), or ARIEL (TMC114-TiDP29-C228) studies were eligible to participate if they derived benefit from using DRV/r in countries where it was not available to them. DRV/r dosing was continued based on original study protocols. Only safety data were collected. Reportable adverse events (AEs) included AEs considered at least possibly related to treatment with DRV/r, AEs leading to discontinuation or treatment interruption, and serious AEs (SAEs).

Results: Forty-six patients rolled over to this study and received at least one dose of DRV/r. Median duration of DRV/r intake was 4.2 years. Overall, 15/46 patients experienced one or more reportable AEs, 10/46 patients experienced one or more grade 3 or 4 AEs, and 12/46 patients experienced one or more SAEs. The most common grade 3 or 4 and SAEs were pneumonia (3/46) and asthma (2/46). Only one AE (grade 1 lipoatrophy) was considered probably related to DRV/r (DIONE, n = 1). Overall, 3/46 patients experienced an HIV-related AE (grade 3 pneumonia SAE; grade 2 tuberculosis SAE, and grade 2 lipoatrophy AE), none of which were considered related to DRV/r or led to study discontinuation. Two AEs leading to discontinuation were pregnancies.

Conclusion: These long-term safety results continue to support DRV/r as a valuable therapeutic option for the treatment of HIV-1 infection in pediatric patients aged ≥ 3 years.

Trial registration: ClinicalTrials.gov: NCT01138605/EudraCT number: 2009-017013-29; first submitted 8 April 2010.

Publication types

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

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Darunavir* / adverse effects
  • Follow-Up Studies
  • HIV Infections* / drug therapy
  • HIV Protease Inhibitors / adverse effects
  • HIV-1*
  • Health Services Accessibility
  • Humans
  • Ritonavir* / adverse effects

Substances

  • HIV Protease Inhibitors
  • Ritonavir
  • Darunavir

Associated data

  • ClinicalTrials.gov/NCT01138605
  • EudraCT/2009-017013-29