PMID- 26066346
OWN - NLM
STAT- MEDLINE
DCOM- 20160516
LR  - 20220316
IS  - 1758-2652 (Electronic)
IS  - 1758-2652 (Linking)
VI  - 18
IP  - 1
DP  - 2015
TI  - PRINCE-1: safety and efficacy of atazanavir powder and ritonavir liquid in 
      HIV-1-infected antiretroviral-naive and -experienced infants and children aged >/=3 
      months to <6 years.
PG  - 19467
LID - 10.7448/IAS.18.1.19467 [doi]
LID - 19467 [doi]
AB  - INTRODUCTION: PRINCE-1 is an ongoing prospective, international, multicentre, 
      nonrandomized, two-stage clinical trial assessing safety and efficacy of 
      once-daily atazanavir (ATV) powder boosted with ritonavir (RTV) liquid plus 
      optimized dual nucleoside reverse-transcriptase inhibitor (NRTI) background 
      therapy in antiretroviral (ARV)-naive and -experienced children with HIV-1 
      infection aged >/=3 months to <6 years. METHODS: Children with HIV-1 infection 
      without prior ATV exposure and with a screening HIV-1 RNA >/=1000 copies/mL were 
      enrolled. The dosing of ATV powder, boosted with 80 mg RTV liquid, was based on 
      three baseline weight bands (5 to <10 kg=150 mg, 10 to <15 kg=200 mg and 15 to 
      <25 kg=250 mg). RESULTS: Of the 56 treated patients, 46 completed 48 weeks of 
      therapy, 67.9% were from Africa and 60.7% were ART-naive. Median ages at baseline 
      were 6, 35 and 55 months, and proportions with HIV-1 RNA >100,000 were 85.7, 52.6 
      and 25% in the three baseline weight bands, respectively. No unexpected safety 
      events occurred and no deaths were reported. Over 48 weeks, upper respiratory 
      tract infections, diarrhoea, vomiting and Grade 3 to 4 hyperbilirubinaemia 
      occurred in 35.7, 35.7, 28.6, and 9.4% of patients, respectively; five patients 
      (8.9%) discontinued due to adverse events (AEs); and 11 patients (19.6%) 
      experienced serious adverse events. At Week 48, using a modified intent-to-treat 
      analysis (two patients were excluded because they switched to ATV capsules before 
      Week 48), 61.1 and 74.1% of patients overall had an HIV-1 RNA level <50 copies/mL 
      and <400 copies/mL, respectively. Virologic suppression rates increased across 
      the lowest to highest baseline weight bands (47.6, 68.4 and 71.4% had HIV-1 RNA 
      <50 copies/mL, and 66.7, 73.7 and 85.7% had HIV-RNA <400 copies/mL, respectively) 
      but did not differ meaningfully between ARV-naive and -experienced patients. 
      Overall, the median change from baseline in CD4 cell count was +363 cells/mm(3), 
      and the median change from baseline in CD4 percent was +7.5%. CONCLUSIONS: ATV 
      powder boosted with RTV liquid once daily plus optimized dual NRTI background 
      therapy was effective and well tolerated in this ART-naive or -experienced 
      paediatric population aged >/=3 months to <6 years. No unexpected safety findings 
      compared with those from previous ATV paediatric and adult studies were 
      identified.
FAU - Strehlau, Renate
AU  - Strehlau R
AD  - Rahima Moosa Mother & Child Hospital, Johannesburg, South Africa;
FAU - Donati, Anamaria Pena
AU  - Donati AP
AD  - Hospital Sotero Del Rio, Santiago, Chile.
FAU - Arce, Pedro Martinez
AU  - Arce PM
AD  - Hospital Civil Fray Antonio Alcade, Guadalajara, Mexico.
FAU - Lissens, Jurgen
AU  - Lissens J
AD  - Bristol-Myers Squibb Research and Development, Braine L'Alleud, Belgium.
FAU - Yang, Rong
AU  - Yang R
AD  - Bristol-Myers Squibb Research and Development, Wallingford, CT, USA.
FAU - Biguenet, Sophie
AU  - Biguenet S
AD  - AbbVie, North Chicago, IL, USA.
FAU - Cambilargiu, Daniela
AU  - Cambilargiu D
AD  - Bristol-Myers Squibb Research and Development, Buenos Aires, Argentina.
FAU - Hardy, Helene
AU  - Hardy H
AD  - Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
FAU - Correll, Todd
AU  - Correll T
AD  - Bristol-Myers Squibb Research and Development, Princeton, NJ, USA; 
      todd.correll@bms.com.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150610
PL  - Switzerland
TA  - J Int AIDS Soc
JT  - Journal of the International AIDS Society
JID - 101478566
RN  - 0 (Anti-HIV Agents)
RN  - 4MT4VIE29P (Atazanavir Sulfate)
RN  - O3J8G9O825 (Ritonavir)
SB  - IM
MH  - Anti-HIV Agents/*administration & dosage
MH  - Atazanavir Sulfate/*administration & dosage
MH  - Child
MH  - Child, Preschool
MH  - Drug Therapy, Combination
MH  - Female
MH  - HIV Infections/*drug therapy
MH  - *HIV-1/drug effects
MH  - Humans
MH  - Infant
MH  - Male
MH  - Prospective Studies
MH  - Ritonavir/*administration & dosage
PMC - PMC4463476
OTO - NOTNLM
OT  - HIV-1 infection
OT  - antiretroviral therapy
OT  - atazanavir powder
OT  - child
OT  - infant
OT  - paediatric formulations
OT  - ritonavir liquid
EDAT- 2015/06/13 06:00
MHDA- 2016/05/18 06:00
PMCR- 2015/06/10
CRDT- 2015/06/13 06:00
PHST- 2014/09/23 00:00 [received]
PHST- 2015/03/05 00:00 [revised]
PHST- 2015/04/13 00:00 [accepted]
PHST- 2015/06/13 06:00 [entrez]
PHST- 2015/06/13 06:00 [pubmed]
PHST- 2016/05/18 06:00 [medline]
PHST- 2015/06/10 00:00 [pmc-release]
AID - 19467 [pii]
AID - 10.7448/IAS.18.1.19467 [doi]
PST - epublish
SO  - J Int AIDS Soc. 2015 Jun 10;18(1):19467. doi: 10.7448/IAS.18.1.19467. eCollection 
      2015.