Immune Reconstitution but Persistent Activation After 48 Weeks of Antiretroviral Therapy in Youth With Pre-Therapy CD4 >350 in ATN 061.
BACKGROUND
Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited.


METHODS
Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell subsets and markers of T-cell and macrophage activation in subjects with pre-therapy CD4 > 350 cells/mm. All subjects had optimal viral suppression from weeks 24 through 48.


METHODS
Subjects (n = 48) initiated cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls.


RESULTS
Significant increases over 48 weeks were noted in all CD4 populations, including total, naive, central memory (CM), and effector memory RO (EM RO) and effector memory RA (EM RA), whereas numbers of CM and EM RO CD8 cells declined significantly. By week 48, CD4 naive cells were similar to controls, whereas CM CD4 cells remained significantly lower and EM RO and EM RA subsets were significantly higher. CD38 and HLA DR expression, both individually and when co-expressed, decreased over 48 weeks of cART on CD8 cells but remained significantly higher than controls at week 48. In contrast, markers of macrophage activation measured by sCD14 and sCD163 in plasma did not change with cART and were significantly higher than controls.


CONCLUSIONS
In youth initiating early cART, CD4 cell reconstitution is robust with decreases in CD8 cells. However, CD8 T-cell and macrophage activation persists at higher levels than uninfected controls.
*New York University School of Medicine, New York, NY; †The Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, Bethesda, MD; ‡Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA; §Westat, Rockville, MD; ‖University of Alabama at Birmingham; ¶Johns Hopkins School of Medicine; #University of South Florida School of Medicine, Tampa, FL; **University of Florida Health Science Center, Gainsville, FL; and ††Duke University School of Medicine, Durham, NC.
Bret J
BJ
Rudy
Bill G
BG
Kapogiannis
Carol
C
Worrell
Kathleen
K
Squires
James
J
Bethel
Su
S
Li
Craig M
CM
Wilson
Allison
A
Agwu
Patricia
P
Emmanuel
Georgine
G
Price
Stephanie
S
Hudey
Maureen M
MM
Goodenow
John W
JW
Sleasman
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008297:Male; D013997:Time Factors; D055815:Young Adult
D019380:Anti-HIV Agents