232 - Abstract (11th CROI)

Session 43 Poster Abstracts
Cellular Responses under HAART
Monday, 1:30 - 3:30 pm
Poster Hall

232
ACTG 5015: Naīve T-cell Reconstitution is Associated with Immune Activation
R Kalayjian*¹, A Landay², R Pollard³, M Pu⁴, J Spritzer⁴, P Tebas⁵, B Gross⁶, V Valcour⁷, S Cu-Uvin⁸, S Fiscus⁹, P Fidel¹⁰, A Wu¹¹, L Fox¹², V Stocker¹³, M Lederman¹⁴, and AIDS Clinical Trials Group Protocol 5015
¹MetroHlth. Med Ctr, Cleveland, OH, USA; ²Rush-Presbyterian, Chicago, IL, USA; ³Univ. of California, Davis, USA; ⁴Harvard Sch. of Publ. Hlth., Boston, MA, USA; ⁵Univ. of Pennsylvania, Philadephia, USA; ⁶Univ. of Michigan, Ann Arbor, USA; ⁷Univ. of Hawaii, Honolulu, USA; ⁸Brown Univ. Med. Sch., Providence, RI, USA; ⁹Univ. of North Carolina at Chapel Hill, USA; ¹⁰Louisiana State Univ, New Orleans, LA, USA; ¹¹Johns Hopkins Univ., Baltimore, MD, USA; ¹²DAIDS, NIAID, NIH, DHHS, Bethesda, MD, USA; ¹³AACTG Operations Ctr., Bethesda, MD, USA; and ¹⁴Case Western Reserve Univ., Cleveland, OH, USA

Background: Naīve T cells, thought to represent key immunologic reserves, are often depleted in HIV disease. Immune activation may play an important role in this deficiency. The goal of this study was to identify correlates of naīve CD4 and CD8 cell numbers before treatment and after 48 weeks of HAART.

Methods: ACTG 5015 is a prospective, multi-center cohort study of older (45 years or older) vs younger (30 years or younger) HIV-infected subjects who received LPV/rtv + d4T + FTC. Age-matched, healthy HIV^- controls were included for baseline comparisons. First (week 0 to 8) and second (week 8 to 48) phase changes in naīve T-cells were correlated with markers of immune activation (%HLA-DR/CD38 expression; serum TNF-α and TNFR-II), thymic indices (thymus volume by CT scan; TREC DNA content in PBMCs as copies of TREC DNA/μg genomic DNA), spontaneous lymphocyte apoptosis and HIV-RNA. Spearman rank correlations were performed with ordinal variables and Wilcoxon-based shift parameters were calculated when comparing sub-groups of subjects.

Results: We included 91 HIV⁺ subjects and 48 HIV^- controls for the baseline comparisons; 79 HIV⁺ subjects were included in the 48 wk analysis. Among both healthy and HIV+ subjects, baseline naīve T cells were positively correlated with thymic volumes and TREC content. In addition in HIV⁺ subjects, but not in controls, CD4 and CD8 cells were correlated negatively with markers of immune activation (%CD4/HLA-DR/CD38), and for CD4 but not CD8 cells, with serum TNF-RII, spontaneous apoptosis and HIV RNA. First and second phase increases in naīve CD4 cell counts were correlated with treatment induced decreases in immune activation (CD8/HLA-DR/CD38%). Also, the magnitude of second phase naive CD4 cell increases was negatively predicted by baseline serum TNF-α levels. On the other hand, first phase naīve CD8 cell increases were predicted by baseline HIV-RNA; second phase changes were not associated with any of the markers examined.

Conclusions: Among untreated HIV⁺ subjects, both markers of thymic activity and immune activation reflected naīve T cell counts. HAART-induced changes in naīve CD4 cells were correlated with markers of immune activation, while only HIV RNA levels predicted the early increases in naīve CD8 cells. Our data support the importance of immune activation in naīve T cell homeostasis with HIV infection.

Keywords: Immue activation; T cell homeostasis; Thymus