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)

• 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
• ISSN: 0891-3668; 1532-0987
• DOI: 10.1097/INF.0000000000000308

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.