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

Flynn, Patricia MD*; Komar, Svitlana MD; Blanche, Stephane MD; Giaquinto, Carlo MD§; Noguera-Julian, Antoni MD, PhD; Welch, Steven MRCPCH; Lathouwers, Erkki MSc**; Van de Casteele, Tom PhD**; Kakuda, Thomas N. PharmD††; Opsomer, Magda MD**

Pediatric Infectious Disease Journal: September 2014 - Volume 33 - Issue 9 - p 940–945
doi: 10.1097/INF.0000000000000308
HIV Reports

Background: Twice-daily darunavir/ritonavir is indicated in treatment-experienced children (≥3 years). This study assessed once-daily administration in treatment-naïve adolescents.

Methods: 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.

Results: 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/mm3 (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.

Conclusions: 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.

From the *Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN; Clinic for Treatment of HIV-infected Children, Kiev Children’s Hospital, Kiev, Ukraine; Department of Pediatric Immuno-Hematology, Hôpital Necker-Enfants Malades, Paris, France; §Department of Paediatrics, University of Padova, Padova, Italy; Department of Pediatrics, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain; Department of Pediatrics, Birmingham Heartlands Hospital, Birmingham, United Kingdom; **Janssen Research & Development LLC, Titusville, NJ; and ††Janssen Research & Development, Beerse, Belgium.

Accepted for publication February 5, 2014.

P.F. has received grants from Tibotec/Johnson & Johnson, consultancy fees from Merck and royalties from UpToDate. C.G. has received grants from Johnson & Johnson, Gilead and Bristol-Myers Squibb. A.N.-J. has been an investigator for Janssen. E.L. is a full-time employee of Janssen. T.V.d.C. and T.N.K. are full-time employees of Janssen and own Johnson & Johnson stock. M.O. is a full-time employee of Janssen and owns Janssen stock.

This study was sponsored by Janssen Research & Development. The authors have no other funding or conflicts of interest to disclose.

Presented as “Giaquinto C, Flynn P, Blanche S, et al. Darunavir/ritonavir once daily in treatment-naïve adolescents: 48-week efficacy, safety, tolerability and pharmacokinetic results of the DIONE study” at the 4th International Workshop on HIV Pediatrics, July 20–21, 2012, Washington, DC. Poster P_13; and at the XIX International AIDS Conference, July 22–27, 2012, Washington, DC. Poster P_MOPE037.

Address for Correspondence: Patricia Flynn, MD, Department of Infectious Diseases, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105. E-mail: pat.flynn@stjude.org.

© 2014 by Lippincott Williams & Wilkins, Inc.