Research Article: Comparing longitudinal CD4 responses to cART among non-perinatally HIV-infected youth versus adults: Results from the HIVRN Cohort

Date Published: February 9, 2017

Publisher: Public Library of Science

Author(s): Allison L. Agwu, John A. Fleishman, Guy Mahiane, Bareng Aletta Sanny Nonyane, Keri N. Althoff, Baligh R. Yehia, Stephen A. Berry, Richard Rutstein, Ank Nijhawan, Christopher Mathews, Judith A. Aberg, Jeanne C. Keruly, Richard D. Moore, Kelly A. Gebo, Alan Landay.


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).

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).

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.

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.

Partial Text

Thirty years into the HIV epidemic, effective combination antiretroviral therapy (cART) has transformed HIV into a chronic disease. Life expectancy for persons living with HIV (PLHIV) has improved dramatically, mirroring that of uninfected adults. [1,2] However, non-perinatally HIV-infected (nPHIV) youth between the ages of 13 and 24 comprise a unique and challenging group, in which the incidence of HIV infection is increasing. [3] Youth tend to have higher CD4 counts than adults when presenting for care, though 40% have CD4 counts below 350 cells/mm3 at presentation. [4,5] [6–10]

This retrospective study compared trends in CD4 levels over time after initiation of cART between nPHIV youth aged 13–24 and adults aged 25 through 44 years at study entry. Studies that have examined differences in immunologic responses between young and older adults have used varying age comparisons,[28–30] e.g., 18–30 vs. 30–40, 40–50, 50-<60 and ≥60 [31], ≥16-<32.7 vs. 32.7–37.4, 27.2–44.4, and ≥44.5 [32], <50 vs. ≥50 years of age. [24,33] Differences between younger and older adults tended to emerge when comparing younger individuals with those ≥50 [24], with a few studies finding differences when comparing younger individuals to those > = 44.5 and 40–50 years of age.[31,32] Notably, most of the studies lumped all younger adults (e.g., 18–49) and had limited numbers of the youngest patients (i.e., <24), making it challenging to decipher differences in immune responses to cART among the youngest age groups. We therefore intentionally chose 45 as the upper age cutoff for our study to specifically compare CD4 response to cART among individuals where it would least be expected, by the cumulative evidence, that there should be differences and where any differences seen would not be attributed to the expected changes with older age. Initially, 3,110 individuals were eligible for analysis. Of these, we excluded 246 (8%) whose baseline CD4 test occurred more than 16 weeks before the start of cART, 206 (6%) who had no CD4 test after cART, 58 (2%) whose first recorded CD4 test was after cART initiation, and 5 (<1%) missing all VL data. Analyses of a large cohort of young PLHIV receiving cART reveals three major findings: youth who start cART do so at higher CD4 counts compared to older adults; youth have better initial CD4 responses than older adults; and, possibly due to decreased adherence, youth’s CD4 response plateaus, allowing adults to reach similar CD4 levels after sufficient time has passed.   Source: