Long-term safety and efficacy of atazanavir-based therapy in HIV-infected infants, children and adolescents: The Pediatric AIDS Clinical Trials Group Protocol 1020A

PACTG 1020A Study Team

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Atazanavir (ATV) is an attractive option for the treatment of Pediatric HIV infection, based on once-daily dosing and the availability of a formulation appropriate for younger children. Pediatric AIDS Clinical Trials Group 1020A was a phase I/II open label study of ATV (with/without ritonavir [RTV] boosting)-based treatment of HIV-infected children; here we report the long-term safety and virologic and immunologic responses. Methods: Antiretroviral-naïve and experienced children, ages 91 days to 21 years, with baseline plasma HIV RNA > 5000 copies/mL (cpm) were enrolled at sites in the United States and South Africa. Results: Of 195 children enrolled, 142 (73%) subjects received ATV-based regimens at the final protocol recommended dose; 58% were treatment naive. Overall, at week 24, 84/139 subjects (60.4%) and at week 48, 83/142 (58.5%) had HIV RNA ≤ 400 cpm. At week 48, 69.5% of naïve and 43.3%of experienced subjects had HIV RNA ≤ 400 cpm; median CD4 increasewas 196.5 cells/mm3. The primary adverse event (AE) was increased serumbilirubin; 9% of subjects had levels ≥ 5.1 times upper limit of normal (ULN) and 1.4% noted jaundice. Three percent of subjects experienced grade 2 or 3 prolongation in PR or QTc intervals. At week 48, there was a 15% increase in total cholesterol (TC), with TC > 199 mg/dL increasing from 1% at baseline to 5.7%. Conclusions: Use of once-daily ATV, with/without RTV, was safe and well tolerated in children, with acceptable levels of viral suppression and CD4 count increase. The primary AE, as expected, was an increase in bilirubin levels.

Original languageEnglish (US)
Pages (from-to)162-167
Number of pages6
JournalJournal of Pediatric Infectious Diseases
Volume34
Issue number2
DOIs
StatePublished - Jan 1 2015

Fingerprint

Clinical Protocols
Acquired Immunodeficiency Syndrome
Clinical Trials
HIV
Pediatrics
Safety
Ritonavir
RNA
Cholesterol
Therapeutics
CD4 Lymphocyte Count
South Africa
Jaundice
Bilirubin
HIV Infections
Atazanavir Sulfate

Keywords

  • Antiretroviral treatment
  • Atazanavir
  • Pediatric HIV

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Infectious Diseases

Cite this

@article{ff9ee0b31e374d4b82b2a1165fbb1c90,
title = "Long-term safety and efficacy of atazanavir-based therapy in HIV-infected infants, children and adolescents: The Pediatric AIDS Clinical Trials Group Protocol 1020A",
abstract = "Background: Atazanavir (ATV) is an attractive option for the treatment of Pediatric HIV infection, based on once-daily dosing and the availability of a formulation appropriate for younger children. Pediatric AIDS Clinical Trials Group 1020A was a phase I/II open label study of ATV (with/without ritonavir [RTV] boosting)-based treatment of HIV-infected children; here we report the long-term safety and virologic and immunologic responses. Methods: Antiretroviral-na{\"i}ve and experienced children, ages 91 days to 21 years, with baseline plasma HIV RNA > 5000 copies/mL (cpm) were enrolled at sites in the United States and South Africa. Results: Of 195 children enrolled, 142 (73{\%}) subjects received ATV-based regimens at the final protocol recommended dose; 58{\%} were treatment naive. Overall, at week 24, 84/139 subjects (60.4{\%}) and at week 48, 83/142 (58.5{\%}) had HIV RNA ≤ 400 cpm. At week 48, 69.5{\%} of na{\"i}ve and 43.3{\%}of experienced subjects had HIV RNA ≤ 400 cpm; median CD4 increasewas 196.5 cells/mm3. The primary adverse event (AE) was increased serumbilirubin; 9{\%} of subjects had levels ≥ 5.1 times upper limit of normal (ULN) and 1.4{\%} noted jaundice. Three percent of subjects experienced grade 2 or 3 prolongation in PR or QTc intervals. At week 48, there was a 15{\%} increase in total cholesterol (TC), with TC > 199 mg/dL increasing from 1{\%} at baseline to 5.7{\%}. Conclusions: Use of once-daily ATV, with/without RTV, was safe and well tolerated in children, with acceptable levels of viral suppression and CD4 count increase. The primary AE, as expected, was an increase in bilirubin levels.",
keywords = "Antiretroviral treatment, Atazanavir, Pediatric HIV",
author = "{PACTG 1020A Study Team} and Rutstein, {Richard M.} and Pearl Samson and Terry Fenton and Fletcher, {Courtney V} and Kiser, {Jennifer J.} and Mofenson, {Lynne M.} and Elizabeth Smith and Bobbie Graham and Marina Mathew and Grace Aldrovani",
year = "2015",
month = "1",
day = "1",
doi = "10.1097/INF.0000000000000538",
language = "English (US)",
volume = "34",
pages = "162--167",
journal = "Journal of Pediatric Infectious Diseases",
issn = "1871-0336",
publisher = "IOS Press",
number = "2",

}

TY - JOUR

T1 - Long-term safety and efficacy of atazanavir-based therapy in HIV-infected infants, children and adolescents

T2 - The Pediatric AIDS Clinical Trials Group Protocol 1020A

AU - PACTG 1020A Study Team

AU - Rutstein, Richard M.

AU - Samson, Pearl

AU - Fenton, Terry

AU - Fletcher, Courtney V

AU - Kiser, Jennifer J.

AU - Mofenson, Lynne M.

AU - Smith, Elizabeth

AU - Graham, Bobbie

AU - Mathew, Marina

AU - Aldrovani, Grace

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: Atazanavir (ATV) is an attractive option for the treatment of Pediatric HIV infection, based on once-daily dosing and the availability of a formulation appropriate for younger children. Pediatric AIDS Clinical Trials Group 1020A was a phase I/II open label study of ATV (with/without ritonavir [RTV] boosting)-based treatment of HIV-infected children; here we report the long-term safety and virologic and immunologic responses. Methods: Antiretroviral-naïve and experienced children, ages 91 days to 21 years, with baseline plasma HIV RNA > 5000 copies/mL (cpm) were enrolled at sites in the United States and South Africa. Results: Of 195 children enrolled, 142 (73%) subjects received ATV-based regimens at the final protocol recommended dose; 58% were treatment naive. Overall, at week 24, 84/139 subjects (60.4%) and at week 48, 83/142 (58.5%) had HIV RNA ≤ 400 cpm. At week 48, 69.5% of naïve and 43.3%of experienced subjects had HIV RNA ≤ 400 cpm; median CD4 increasewas 196.5 cells/mm3. The primary adverse event (AE) was increased serumbilirubin; 9% of subjects had levels ≥ 5.1 times upper limit of normal (ULN) and 1.4% noted jaundice. Three percent of subjects experienced grade 2 or 3 prolongation in PR or QTc intervals. At week 48, there was a 15% increase in total cholesterol (TC), with TC > 199 mg/dL increasing from 1% at baseline to 5.7%. Conclusions: Use of once-daily ATV, with/without RTV, was safe and well tolerated in children, with acceptable levels of viral suppression and CD4 count increase. The primary AE, as expected, was an increase in bilirubin levels.

AB - Background: Atazanavir (ATV) is an attractive option for the treatment of Pediatric HIV infection, based on once-daily dosing and the availability of a formulation appropriate for younger children. Pediatric AIDS Clinical Trials Group 1020A was a phase I/II open label study of ATV (with/without ritonavir [RTV] boosting)-based treatment of HIV-infected children; here we report the long-term safety and virologic and immunologic responses. Methods: Antiretroviral-naïve and experienced children, ages 91 days to 21 years, with baseline plasma HIV RNA > 5000 copies/mL (cpm) were enrolled at sites in the United States and South Africa. Results: Of 195 children enrolled, 142 (73%) subjects received ATV-based regimens at the final protocol recommended dose; 58% were treatment naive. Overall, at week 24, 84/139 subjects (60.4%) and at week 48, 83/142 (58.5%) had HIV RNA ≤ 400 cpm. At week 48, 69.5% of naïve and 43.3%of experienced subjects had HIV RNA ≤ 400 cpm; median CD4 increasewas 196.5 cells/mm3. The primary adverse event (AE) was increased serumbilirubin; 9% of subjects had levels ≥ 5.1 times upper limit of normal (ULN) and 1.4% noted jaundice. Three percent of subjects experienced grade 2 or 3 prolongation in PR or QTc intervals. At week 48, there was a 15% increase in total cholesterol (TC), with TC > 199 mg/dL increasing from 1% at baseline to 5.7%. Conclusions: Use of once-daily ATV, with/without RTV, was safe and well tolerated in children, with acceptable levels of viral suppression and CD4 count increase. The primary AE, as expected, was an increase in bilirubin levels.

KW - Antiretroviral treatment

KW - Atazanavir

KW - Pediatric HIV

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