Efficacy and Safety of Darunavir/Ritonavir at 48 Weeks in Treatment-naïve, HIV-1-infected Adolescents: Results From a Phase 2 Open-label Trial (DIONE)

Twice-daily darunavir/ritonavir is indicated in treatment-experienced children (≥3 years). This study assessed once-daily administration in treatment-naïve adolescents. Phase 2, 48-week, open-label, single-arm study evaluating pharmacokinetics, safety and efficacy of once-daily darunavir/ritonavir 8...

Full description

Saved in:

Bibliographic Details
Published in:	The Pediatric infectious disease journal Vol. 33; no. 9; pp. 940 - 945
Main Authors:	FLYNN, Patricia, KOMAR, Svitlana, BLANCHE, Stephane, GIAQUINTO, Carlo, NOGUERA-JULIAN, Antoni, WELCH, Steven, LATHOUWERS, Erkki, VAN DE CASTEELE, Tom, KAKUDA, Thomas N, OPSOMER, Magda
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 01-09-2014
Subjects:	Adolescent Anemia - chemically induced Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences CD4 Lymphocyte Count Darunavir Dideoxynucleosides - therapeutic use Drug Resistance, Viral Drug Therapy, Combination Female HIV Infections - drug therapy HIV Infections - immunology HIV Protease Inhibitors - pharmacokinetics HIV Protease Inhibitors - therapeutic use HIV-1 Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Infectious diseases Lamivudine - therapeutic use Male Medical sciences Medication Adherence Nausea - chemically induced Neutropenia - chemically induced Pharmacology. Drug treatments Reverse Transcriptase Inhibitors - therapeutic use Ritonavir - pharmacokinetics Ritonavir - therapeutic use Sulfonamides - pharmacokinetics Sulfonamides - therapeutic use Time Factors Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load - drug effects Vomiting - chemically induced Zidovudine - therapeutic use HIV-1 Pediatrics Antiretroviral agent Darunavir HIV-1 virus Ritonavir treatment-naïve Non peptide compound Antiviral Human Immunopathology Enzyme adolescents Enzyme inhibitor Retroviridae AIDS Immune deficiency Lentivirus Infection Virus Peptidases Viral disease Adolescent Hydrolases Human immunodeficiency virus Protease inhibitor
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Twice-daily darunavir/ritonavir is indicated in treatment-experienced children (≥3 years). This study assessed once-daily administration in treatment-naïve adolescents. Phase 2, 48-week, open-label, single-arm study evaluating pharmacokinetics, safety and efficacy of once-daily darunavir/ritonavir 800/100 mg in treatment-naïve, HIV-1-infected adolescents (≥12 to <18 years, ≥40 kg) with zidovudine/lamivudine or abacavir/lamivudine. Twelve patients (67% female; median 14.4 years) were enrolled. After 24 and 48 weeks, respectively, 11 of 12 (92%) and 10 of 12 (83%) patients achieved viral load <50 copies/mL (intent-to-treat time-to-loss of virologic response); all had ≥1 log10 drop in viral load versus baseline. Median CD4 cell count increased by 175 and 221 cells/mm (intent-to-treat-noncompleter = failure) after 24 and 48 weeks, respectively. Eighty-three percent of patients were adherent to darunavir/ritonavir. One patient was never suppressed and 1 patient rebounded. No patients developed darunavir resistance-associated mutations or lost phenotypic susceptibility to any commercially available protease inhibitor or any background nucleoside reverse transcriptase inhibitor. Eleven patients (92%) reported ≥1 adverse event (AE), considered in 2 patients to be at least possibly related to darunavir (gastrointestinal-related events and dizziness). Four patients had ≥1 serious AE. Three patients reported ≥1 grade 3/4 AE; no serious or grade 3/4 AEs were considered darunavir related. No patients discontinued because of AEs. Over 48 weeks, once-daily darunavir/ritonavir 800/100 mg plus NRTIs was effective and well-tolerated for treatment of HIV-1-infected, antiretroviral-naïve adolescents (≥12 to <18 years). These findings support use of once-daily darunavir/ritonavir 800/100 mg in this population.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0891-3668 1532-0987
DOI:	10.1097/INF.0000000000000308