title: Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus-Infected Youth.
abstract: As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care.
  
  
  
  To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status.
  
  
  
  Combining data from the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 multicenter cohort studies (March 2007 through April 2015), we estimated event rates during person-time spent in key strata of age (7-12, 13-17, and 18-30 years), CD4 cell count (<200, 200-499, and ≥500/μL), and a combined measure of VL and ARV status (VL <400 or ≥400 copies/mL; ARV therapy or no ARV therapy). A total of 1562 participants in the PHACS Adolescent Master Protocol and IMPAACT P1074 were eligible, and 1446 PHIVY from 41 ambulatory sites in the 12 US states, including Puerto Rico were enrolled. The dates of analysis were March 2015 through January 2017.
  
  
  
  Clinical event rates stratified by person-time in age, CD4 cell count, and VL and ARV categories.
  
  
  
  A total of 1446 PHIVY participated in the study (mean [SD] age, 14.6 [4.6] years; 759 female [52.5%]; 953 black [65.9%]). During a mean (SD) follow-up of 4.9 (1.3) years, higher incidences of CDC-B events, CDC-C events, and mortality were observed as participants aged. Older PHIVY (aged 13-17 and 18-30 years) spent more time with a VL of 400 copies/mL or more and with a CD4 cell count of less than 200/µL compared with 7- to 12-year-old participants (30% and 44% vs 22% of person-time with a VL≥400 copies/mL; 5% and 18% vs 2% of person-time with CD4 cell count <200/µL; P < .001 for each comparison). We observed higher rates of CDC-B events, CDC-C events, bacterial infections, and mortality at lower CD4 cell counts, as expected. The mortality rate among older PHIVY was 6 to 12 times that among the general US population. Higher rates of sexually transmitted infections were also observed at lower CD4 cell counts after adjusting for age.
  
  
  
  Older PHIVY were at increased risk of viremia, immunosuppression, CDC-B events, CDC-C events, and mortality. Interventions to improve ARV therapy adherence and optimize models of care for PHIVY as they age are urgently needed to improve long-term outcomes among PHIVY.
authors.affiliation: Division of Infectious Diseases and the Medical Practice Evaluation Center, Massachusetts General Hospital, Boston2Department of Pediatrics, Massachusetts General Hospital, Boston3Harvard Medical School, Harvard University, Boston, Massachusetts.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Neilan
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Brad
authors.initials: B
authors.lastname: Karalius
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts5Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Kunjal
authors.initials: K
authors.lastname: Patel
authors.affiliation: Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.affiliation: Department of Pediatrics (Infectious Diseases), University of Colorado School of Medicine and Children's Hospital, Aurora.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Abzug
authors.affiliation: Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Agwu
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts5Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.affiliation: Bronx-Lebanon Hospital Center, Icahn School of Medicine at Mt. Sinai, New York, New York.
authors.forename: Murli
authors.initials: M
authors.lastname: Purswani
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kacanek
authors.affiliation: Division of Pediatric Allergy, Immunology and Infectious Diseases, New Jersey Medical School at Rutgers, Newark.
authors.forename: James M
authors.initials: JM
authors.lastname: Oleske
authors.affiliation: Harvard Medical School, Harvard University, Boston, Massachusetts11Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Burchett
authors.affiliation: Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wiznia
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Miriam
authors.initials: M
authors.lastname: Chernoff
authors.affiliation: Harvard Medical School, Harvard University, Boston, Massachusetts4Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts5Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.affiliation: Division of Infectious Diseases and the Medical Practice Evaluation Center, Massachusetts General Hospital, Boston3Harvard Medical School, Harvard University, Boston, Massachusetts.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Ciaranello
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology*; D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000706:statistics & numerical data; D018791:CD4 Lymphocyte Count; D002648:Child; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D007165:Immunosuppression Therapy; D015994:Incidence; D008297:Male; D012307:Risk Factors; D014481:United States; D019562:Viral Load; D014766:Viremia / Q000453:epidemiology*; D055815:Young Adult