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

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

The Pediatric Infectious Disease Journal: June 2018 - Volume 37 - Issue 6 - p e149–e156
doi: 10.1097/INF.0000000000001856
HIV Reports

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 nucleos(t)ide reverse transcriptase inhibitors therapy in antiretroviral-naïve/experienced children with screening HIV-1 RNA ≥1000 copies/mL. Children 3 months to <11 years received ATV + RTV by 5 baseline weight bands: 5 to <10 kg = 150/80 mg; 5 to <10 kg = 200/80 mg; 10 to <15 kg = 200/80 mg; 15 to <25 kg = 250/80 mg; and 25 to <35 kg = 300/100 mg.

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 were upper respiratory tract infections (33.3%), gastroenteritis (28.3%), vomiting (21.2%) and hyperbilirubinemia (18.2%; none leading to treatment discontinuation). Serious adverse events 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 <10 kg = 200/80 mg group, likely because of 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 ≥3 months to <11 years.

From the *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

**Bristol-Myers Squibb, Rueil-Malmaison, France

††Bristol-Myers Squibb, Buenos Aires, Argentina

‡‡Bristol-Myers Squibb, Wallingford, Connecticut

§§Bristol-Myers Squibb, Princeton, New Jersey.

Accepted for publication October 25, 2017.

This study was supported by Bristol-Myers Squibb, the manufacturer of atazanavir. M.F.C. 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. I.T.-E. declares receiving honoraria for speaker engagements for Merck Sharpe & Dohme; Stendhal Pharma, and AbbVie. M.I.G.-T. declares receiving honoraria for speaker engagements for ViiV Healthcare, Janssen-Cilag and AbbVie; she has also received a Gilead fellowship. J.L., L.Z., I.K., D.C., and T.A.C. are all employees of and own stock in Bristol-Myers Squibb. C.P. was an employee of Bristol-Myers Squibb at the time this study was conducted and is now an employee of Gilead Sciences, Inc. A.L. has no conflicts of interest to disclose.

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Address for Correspondence: Mark F. Cotton, MMed, PhD, 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. E-mail: mcot@sun.ac.za.

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