Immune Reconstitution but Persistent Activation After 48 Weeks of Antiretroviral Therapy in Youth With Pre-Therapy CD4 >350 in ATN 061.

TitleImmune Reconstitution but Persistent Activation After 48 Weeks of Antiretroviral Therapy in Youth With Pre-Therapy CD4 >350 in ATN 061.
Publication TypePublication
Year of Publication2015
AuthorsRudy BJ, Kapogiannis BG, Worrell C, Squires K, Bethel J, Li S, Wilson CM, Agwu A, Emmanuel P, Price G, Hudey S, Goodenow MM, Sleasman JW
Corporate AuthorsAdolescent Trials Network for HIVAIDS Interventions
JournalJ Acquir Immune Defic Syndr
Volume69
Issue1
Pagination52-60
Date Published2015 May 01
ISSN1944-7884
KeywordsAdolescent, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cohort Studies, Female, HIV Infections, Humans, Lymphocyte Activation, Macrophage Activation, Male, Time Factors, Young Adult
Abstract

<p><b>BACKGROUND: </b>Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited.</p><p><b>DESIGN: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p>

DOI10.1097/QAI.0000000000000549
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID25942459
PubMed Central IDPMC4452031
Grant ListU01 HD 040533 / HD / NICHD NIH HHS / United States
U01 HD040533 / HD / NICHD NIH HHS / United States
U01 HD 040474 / HD / NICHD NIH HHS / United States
U01 HD040474 / HD / NICHD NIH HHS / United States
UL1 RR025780 / RR / NCRR NIH HHS / United States
U01 HD040497 / HD / NICHD NIH HHS / United States
UL1 RR024131 / RR / NCRR NIH HHS / United States
DA031017 / DA / NIDA NIH HHS / United States
R01 DA031017 / DA / NIDA NIH HHS / United States
R01 DA DA031017 / DA / NIDA NIH HHS / United States
U01 A1068632 / / PHS HHS / United States
M01 RR010284 / RR / NCRR NIH HHS / United States
U01 HD068070 / HD / NICHD NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
U01 HD040481 / HD / NICHD NIH HHS / United States
UL1 RR024134 / RR / NCRR NIH HHS / United States
M01 RR020359 / RR / NCRR NIH HHS / United States