TY - JOUR
T1 - Immune reconstitution but persistent activation after 48 weeks of antiretroviral therapy in youth with pre-therapy CD4 >350 in ATN 061
AU - The Adolescent Trials Network for HIV/AIDS Interventions
AU - Rudy, Bret J.
AU - Kapogiannis, Bill G.
AU - Worrell, Carol
AU - Squires, Kathleen
AU - Bethel, James
AU - Li, Su
AU - Wilson, Craig M.
AU - Agwu, Allison
AU - Emmanuel, Patricia
AU - Price, Georgine
AU - Hudey, Stephanie
AU - Goodenow, Maureen M.
AU - Sleasman, John W.
N1 - Publisher Copyright:
Copyright © 2015 Wolters Kluwer Health, Inc.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Background: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited. Design: 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/mm3. 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.
AB - Background: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited. Design: 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/mm3. 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.
KW - adolescents
KW - antiretroviral therapy
KW - immune reconstitution
KW - inflammation
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UR - http://www.scopus.com/inward/citedby.url?scp=84928394701&partnerID=8YFLogxK
U2 - 10.1097/QAI.0000000000000549
DO - 10.1097/QAI.0000000000000549
M3 - Article
C2 - 25942459
AN - SCOPUS:84928394701
SN - 1525-4135
VL - 69
SP - 52
EP - 60
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 1
ER -