Avy Violari1, Maysseb Masenya2, Stephane Blanche3, Simon Vanveggel4, Veerle Hufkens4, Polan Chetty5, Magda Opsomer4. 1. Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa. violari@mweb.co.za. 2. Shandukani Research Centre, Wits RHI, Johannesburg, South Africa. 3. Pediatric Immunology-Hematology Unit, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP) and Faculté de Médecine Paris Descartes, Paris, France. 4. Janssen Pharmaceutica NV, Beerse, Belgium. 5. Janssen Research and Development, High Wycombe, UK.
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.
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.