title: 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.
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.
  
  
  METHODS
  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 log10VL by 12 months, the new cART group having the largest drop (-1.15 log10VL).
  
  
  CONCLUSIONS
  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.
authors.affiliation: aWits Reproductive Health & HIV Institute (WRHI), University of the Witwatersrand, Johannesburg, South Africa bDepartment of Epidemiology, Center for Biostatistics in AIDS Research (CBAR), Harvard School of Public Health, Boston, Massachusetts cTulane University School of Medicine, New Orleans, Louisiana dEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland eHarvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts fJohns Hopkins University School of Medicine, Baltimore, Maryland gJacobi Medical Center/Family Based Services, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Fairlie
authors.forename: Brad
authors.initials: B
authors.lastname: Karalius
authors.forename: Kunjal
authors.initials: K
authors.lastname: Patel
authors.forename: Russell B
authors.initials: RB
authors.lastname: van Dyke
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernán
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.forename: Allison
authors.initials: A
authors.lastname: Agwu
authors.forename: Andrew
authors.initials: A
authors.lastname: Wiznia
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008297:Male; D011446:Prospective Studies; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents