427. Late-Occurring Alterations in Lymphocyte Populations in HIV-1 infected Individuals During Effective Antiretroviral Therapy
Session: Poster Abstract Session: HIV - Antiretroviral Therapy
Friday, October 21, 2011
Room: Poster Hall B1
Background: The goal of antiretroviral (ARV) is to fully suppress viral replication for many years, enabling restoration of the immune system.  In this context it is important to evaluate recovery from HIV-1–induced damage over extended time periods.  We studied the kinetics of T cell recovery, and influencing variables.

Methods: An observational study at a single institution was performed. Longitudinal plasma HIV-1 RNA level (VL) data from 1996 to 2010 were available for 1086 individuals.  Forty individuals were identified who:  1) had VL > 1000 copies/ml before treatment; 2) remained on effective ARV for more than 6 years; and 3) did not have co-morbidities or treatments that might influence CD4+ T cell recovery.  We tracked changes in CD4+ and CD8+ T cell counts following treatment initiation.  Baseline data (age, gender, CD4+ and CD8+ T cell counts, and VL), and ARV regimens were evaluated for correlations with recovery of T cell populations.  Matlab R2009a software was used to create plots and perform statistical analyses.

Results: Rapid increases in CD4+ T cells and CD4/CD8 ratios were observed during the first 1-2 years of treatment.  Sustained increases in CD4/CD8 ratios were observed for more than 6 years.  Responses were heterogeneous; some with ongoing increases in CD4/CD8 ratios for over 10 years, others with minimal increases, or an early plateau. The slope of CD4/CD8 ratios over the entire time course was remarkably similar between subgroups defined by baseline CD4+ T cell counts (0-200, 201-500, and >500/µl; Thiel estimator values: 0.076, 0.077, and 0.082/year, respectively). The slope of CD4/CD8 over time appeared to have a weak inverse correlation with baseline age (R = -0.287; excluding outliers), but no correlation with gender, baseline CD4+ or CD8+ T cell counts, or baseline VL.  ARV regimens (containing PI vs NNRTI vs Mixture) did not correlate with the slope of CD4/CD8 ratio over time.

Conclusion: For this cohort of individuals on effective ARV, consistent increases in CD4+ T cell and CD4/CD8 ratios were observed over extended periods of time. Only patient age appeared to influence the rate of immune recovery. The findings suggest relatively consistent homeostatic mechanisms that involve the combined populations of CD4+ and CD8+ T cells over at least 6 years.


Subject Category: H. HIV/AIDS and other retroviruses

Thomas Greenough, MD1, David Damiano, PhD2, Maria Cavicchi2, Reagan Savas1, Jennifer Daly, MD1 and Richard Ellison III, MD1, (1)University of Massachusetts Medical School, Worcester, MA, (2)College of the Holy Cross, Worcester, MA

Disclosures:

T. Greenough, None

D. Damiano, None

M. Cavicchi, None

R. Savas, None

J. Daly, None

R. Ellison III, None

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