Comparing longitudinal CD4 responses to cART among non-perinatally HIV-infected youth versus adults: Results from the HIVRN Cohort.
BACKGROUND
Youth have residual thymic tissue and potentially greater capacity for immune reconstitution than adults after initiation of combination antiretroviral therapy (cART). However, youth face behavioral and psychosocial challenges that may make them more likely than adults to delay ART initiation and less likely to attain similar CD4 outcomes after initiating cART. This study compared CD4 outcomes over time following cART initiation between ART-naïve non-perinatally HIV-infected (nPHIV) youth (13-24 years-old) and adults (≥25-44 years-old).


METHODS
Retrospective analysis of ART-naïve nPHIV individuals 13-44 years-old, who initiated their first cART between 2008 and 2011 at clinical sites in the HIV Research Network. A linear mixed model was used to assess the association between CD4 levels after cART initiation and age (13-24, 25-34, 35-44 years), accounting for random variation within participants and between sites, and adjusting for key variables including gender, race/ethnicity, viral load, gaps in care (defined as > 365 days between CD4 tests), and CD4 levels prior to cART initiation (baseline CD4).


RESULTS
Among 2,595 individuals (435 youth; 2,160 adults), the median follow-up after cART initiation was 179 weeks (IQR 92-249). Baseline CD4 was higher for youth (320 cells/mm3) than for ages 25-34 (293) or 35-44 (258). At 239 weeks after cART initiation, median unadjusted CD4 was higher for youth than adults (576 vs. 539 and 476 cells/mm3, respectively), but this difference was not significant when baseline CD4 was controlled. Compared to those with baseline CD4 ≤200 cells/mm3, individuals with baseline CD4 of 201-500 and >500 cells/mm3 had greater predicted CD4 levels: 390, 607, and 831, respectively. Additionally, having no gaps in care and higher viral load were associated with better CD4 outcomes.


CONCLUSIONS
Despite having residual thymic tissue, youth attain similar, not superior, CD4 gains as adults. Early ART initiation with minimal delay is as essential to optimizing outcomes for youth as it is for their adult counterparts.
Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, United States of America.|Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States of America.
Allison L
http://orcid.org/0000-0002-8449-222X
AL
Agwu
Center for Financing, Access, and Cost Trends, Agency for Healthcare Research and Quality, Rockville, MD, United States of America.
John A
JA
Fleishman
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
Guy
G
Mahiane
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
Bareng Aletta Sanny
BA
Nonyane
Bloomberg School of Public Health, Johns Hopkins Medical Institutions, Baltimore, MD, United States of America.
Keri N
KN
Althoff
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States of America.
Baligh R
BR
Yehia
Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States of America.
Stephen A
SA
Berry
Division of General Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
Richard
R
Rutstein
Department of Internal Medicine, UT Southwestern Medical Center, Parkland Health and Hospital System, Dallas TX, United States of America.
Ank
A
Nijhawan
Department of Medicine, University of California San Diego, San Diego, CA, United States of America.
Christopher
C
Mathews
Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Judith A
JA
Aberg
Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States of America.
Jeanne C
JC
Keruly
Division of General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States of America.
Richard D
RD
Moore
Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States of America.
Kelly A
KA
Gebo
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D008297:Male; D016896:Treatment Outcome
D000998:Antiviral Agents