CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States

Pediatric HIV AIDS Cohort Study (PHACS), International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT), George K. Siberry

Research output: Contribution to journalArticle

Abstract

Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) -1.01 to 2.19], not different than those who continued failing cART (71%) (-0.64 percentage points, P=0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P=0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline -3.18 percentage points (95% CI -5.25 to -1.11) compared with those initiating new cART (P=0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log 10 VL by 12 months, the new cART group having the largest drop (-1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring.

Original languageEnglish (US)
Pages (from-to)2109-2119
Number of pages11
JournalAIDS
Volume29
Issue number16
DOIs
StatePublished - Oct 23 2015

Fingerprint

Viral Load
HIV
Therapeutics
Linear Models
Acquired Immunodeficiency Syndrome
Pharmaceutical Preparations
Confidence Intervals
Pediatrics
Clinical Protocols
Group Psychotherapy
Observational Studies
Cohort Studies
Clinical Trials

Keywords

  • CD4 and viral load outcomes
  • HIV-infected children
  • virological failure

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Pediatric HIV AIDS Cohort Study (PHACS), International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT), & Siberry, G. K. (2015). CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States. AIDS, 29(16), 2109-2119. https://doi.org/10.1097/QAD.0000000000000809

CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States. / Pediatric HIV AIDS Cohort Study (PHACS); International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT); Siberry, George K.

In: AIDS, Vol. 29, No. 16, 23.10.2015, p. 2109-2119.

Research output: Contribution to journalArticle

Pediatric HIV AIDS Cohort Study (PHACS), International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) & Siberry, GK 2015, 'CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States', AIDS, vol. 29, no. 16, pp. 2109-2119. https://doi.org/10.1097/QAD.0000000000000809
Pediatric HIV AIDS Cohort Study (PHACS), International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT), Siberry GK. CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States. AIDS. 2015 Oct 23;29(16):2109-2119. https://doi.org/10.1097/QAD.0000000000000809
Pediatric HIV AIDS Cohort Study (PHACS) ; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) ; Siberry, George K. / CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States. In: AIDS. 2015 ; Vol. 29, No. 16. pp. 2109-2119.
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abstract = "Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+{\%} and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40{\%}) children. At 12 months, children switching to new cART (16{\%}) had a nonsignificant increase in CD4+{\%} from baseline, 0.59 percentage points [95{\%} confidence interval (95{\%} CI) -1.01 to 2.19], not different than those who continued failing cART (71{\%}) (-0.64 percentage points, P=0.15) or switched to a drug-sparing regimen (5{\%}) (1.40 percentage points, P=0.64). Children discontinuing all ART (7{\%}) experienced significant CD4+{\%} decline -3.18 percentage points (95{\%} CI -5.25 to -1.11) compared with those initiating new cART (P=0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log 10 VL by 12 months, the new cART group having the largest drop (-1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring.",
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T1 - CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States

AU - Pediatric HIV AIDS Cohort Study (PHACS)

AU - International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT)

AU - Fairlie, Lee

AU - Karalius, Brad

AU - Patel, Kunjal

AU - Van Dyke, Russell B.

AU - Siberry, George K.

AU - Hernán, Miguel A.

AU - Siberry, George K.

AU - Seage, George R.

AU - Agwu, Allison Lorna

AU - Wiznia, Andrew

AU - Shearer, William

AU - Paul, Mary

AU - Cooper, Norma

AU - Harris, Lynette

AU - Purswani, Murli

AU - Baig, Mahboobullah

AU - Cintron, Anna

AU - Puga, Ana

AU - Navarro, Sandra

AU - Patton, Doyle

AU - Leon, Deyana

AU - Burchett, Sandra

AU - Karthas, Nancy

AU - Kammerer, Betsy

AU - Yogev, Ram

AU - Sanders, Margaret Ann

AU - Malee, Kathleen

AU - Hunter, Scott

AU - Burey, Marlene

AU - Nozyce, Molly

AU - Chen, Janet

AU - Ivey, Latreca

AU - Bulkley, Maria Garcia

AU - Grant, Mitzie

AU - Knapp, Katherine

AU - Allison, Kim

AU - Wilkins, Megan

AU - Acevedo-Flores, Midnela

AU - Rios, Heida

AU - Olivera, Vivian

AU - Silio, Margarita

AU - Jones, Medea

AU - Sirois, Patricia

AU - Spector, Stephen

AU - Norris, Kim

AU - Nichols, Sharon

AU - McFarland, Elizabeth

AU - Barr, Emily

AU - McEvoy, Robin

AU - Hutton, Nancy

PY - 2015/10/23

Y1 - 2015/10/23

N2 - Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) -1.01 to 2.19], not different than those who continued failing cART (71%) (-0.64 percentage points, P=0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P=0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline -3.18 percentage points (95% CI -5.25 to -1.11) compared with those initiating new cART (P=0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log 10 VL by 12 months, the new cART group having the largest drop (-1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring.

AB - Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) -1.01 to 2.19], not different than those who continued failing cART (71%) (-0.64 percentage points, P=0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P=0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline -3.18 percentage points (95% CI -5.25 to -1.11) compared with those initiating new cART (P=0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log 10 VL by 12 months, the new cART group having the largest drop (-1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring.

KW - CD4 and viral load outcomes

KW - HIV-infected children

KW - virological failure

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