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Safety and Efficacy of Atazanavir Powder and Ritonavir in HIV-1-Infected Infants and Children Aged From 3 Months to <11 Years: the PRINCE-2 Study

Cotton, Mark, F.*; Liberty, Afaaf; Torres-Escobar, Indiana; Gonzalez-Tome, Maria, Isabel§; Lissens, Jurgen; Zaru, Luna; Klauck, Isabelle#; Cambilargiu, Daniela**; Pikora, Cheryl††; Correll, Todd, A.‡‡

The Pediatric Infectious Disease Journal: December 4, 2017 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/INF.0000000000001856
HIV Reports: PDF Only

Background: Novel antiretroviral formulations that are palatable, safe, and effective are needed for infants and children.

Methods: PRINCE-2 is an ongoing clinical trial assessing safety, efficacy, and palatability of once-daily atazanavir powder formulation boosted with ritonavir (ATV+RTV) plus optimized dual NRTI therapy in ARV-naïve/experienced children with screening HIV-1 RNA ≥1000 copies/mL. Children aged 3 months to <11 years received ATV+RTV by 5 baseline weight bands: 5 to <10kg=150/80mg; 5 to <10kg=200/80mg; 10 to <15kg=200/80mg; 15 to <25kg=250/80mg; and 25 to <35kg=300/100mg.

Results: Of 99 treated children, 83.8% and 59.6% remained on ATV powder until 24 and 48 weeks, respectively. Through 48 weeks, the most common adverse events (AEs) were upper respiratory tract infections (33.3%), gastroenteritis (28.3%), vomiting (21.2%), and hyperbilirubinemia (18.2%; none leading to treatment discontinuation). Serious AEs occurred in 20.2% of patients. Laboratory Grade 3–4 hyperbilirubinemia occurred in 9.2% and elevated total/pancreatic amylase in 33.7%/3.1%. At Week 24, proportions with virologic suppression (HIV-1 RNA <50 copies/mL; intention-to-treat analysis) across weight bands were 10/23 (43.5%), 2/12 (16.5%), 10/21 (47.6%), 19/35 (54.3%), and 5/8 (62.5%), respectively. Virologic suppression was similar in antiretroviral-naïve/experienced patients, and lowest in the 5 to <10kg=200/80mg-group, likely due to higher baseline HIV-1 RNA and discontinuation (66.7%). Overall, virologic suppression at Weeks 24 (46.5%) and 48 (43.0%) was comparable. At Week 48, 83.3% and 74.1% of caregivers reported no trouble giving ATV powder and RTV, respectively.

Conclusions: ATV powder palatability, efficacy and lack of unexpected safety findings support its use for HIV-1-infected children aged ≥3 months to <11 years.

*Children’s Infectious Diseases Clinical Research Unit, Department of Pediatrics & Child Health, Stellenbosch University, Tygerberg, South Africa; Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa; Faculty of Medicine, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico; §Pediatric Infectious Diseases Department, Hospital 12 de Octubre, Madrid, Spain; Bristol-Myers Squibb, Braine L’Alleud, Belgium; Bristol-Myers Squibb, Hopewell, New Jersey, USA; #Bristol-Myers Squibb, Rueil-Malmaison, France; **Bristol-Myers Squibb, Buenos Aires, Argentina; ††Bristol-Myers Squibb, Wallingford, Connecticut, USA; and ‡‡Bristol-Myers Squibb, Princeton, New Jersey, USA

Conflicts of Interest and Source of Funding: This study was supported by Bristol-Myers Squibb, the manufacturer of atazanavir. MFC declares funding for his institution from Bristol-Myers Squibb for the conduct of the present study; his institution has received other funding for pharmaceutical trials from ViiV Healthcare, Gilead Sciences, Novovax, VPM-Gmbh, and Novartis; and NIH funding: NIAID through IMPAACT and ACTG trial networks and NIMH.

AL declares no conflicts of interest.

IT-E declares receiving honoraria for speaker engagements for Merck Sharpe & Dohme; Stendhal Pharma, and AbbVie.

MIG-T declares receiving honoraria for speaker engagements for ViiV, Janssen-Cilag and AbbVie; she has also received a Gilead fellowship.

JL, LZ, IK, DC, and TAC are all employees of and own stock in Bristol-Myers Squibb.

CP was an employee of Bristol-Myers Squibb at the time this study was conducted and is now an employee of Gilead Sciences, Inc.

ACKNOWLEDGMENTS: The authors thank Benjamin Dale and Julian Martins of inScience Communications, Springer Healthcare, who provided medical writing support funded by Bristol-Myers Squibb.

Address for Correspondence: Mark F. Cotton, Faculty of Medicine Health Sciences, Stellenbosch University, Ward J8, Tygerberg Academic Hospital, Francie Van Zijl Drive, Parow Valley, PO Box 241, Cape Town 8000, South Africa. Tel: +27 21 938-4219; Fax: +27 21 938-4153; E-mail:

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