334. Early Effect of Antiretroviral Therapy on Markers of Innate Immune Activation in a Cohort of HIV-infected Patients
Session: Poster Abstract Session: HIV Co-morbidities
Thursday, October 3, 2013
Room: The Moscone Center: Poster Hall C
Background: Immune activation is increased in patients with HIV and predisposes them to accelerated aging as manifested by atherosclerotic cardiovascular disease (ASCVD) and neurocognitive decline.   Long-term antiretroviral therapy (ART) reduces but does not normalize immune activation nor halt progression of these processes.  Little is known about the immediate effects of ART on immune activation.  We describe the early impact of ART on mediators of the innate immune response that have been associated with accelerated aging, including interferon inducible protein-10 (IP-10) and interleukin-6 (IL-6).

Methods: Between July 2008 and December 2011, 32 consecutive HIV-infected patients provided blood samples before and at 2, 4, 6, and 12 weeks after starting ART.  Baseline demographic information and Framingham score were obtained.  ART regimen was chosen by individual medical provider.  Levels of C-reactive protein, fibrinogen, CD4+ T-lymphocytes, HIV viral load, IP-10, tumor necrosis factor-α (TNF-α), interferon- γ (IFN-γ), interleukin-6 (IL-6), and interleukin-10 (IL-10) were obtained using a multiplex electrochemiluminscence assay.  A backward selection procedure was used to fit a regression model to test the effect of ART on biomarker levels while controlling for possible confounders.

Results: Mean age of patients was 36.  Eight of 32 (25%) of patients were women and thirteen (40%) were African-American. Average CD4+ T-lymphocyte count at entry was 387 cells/mm3. There were no significant differences in biomarker levels based on gender.  Levels of IP-10, TNF- α and IL-18 declined after the addition of ART.  The average drop per visit for IP-10, TNF- α and IL-18 was 79,780 pg/mL (p = 0.02), 274 pg/mL (p <0.0001) and 16,342 pg/mL (p= 0.03), respectively).  Levels of IL-6 increased over the study period while levels of IL-10 and IFN- γ remained constant.  Framingham score correlated with IFN- γ with a Pearson correlation coefficient of 0.55 (p value = 0.0013). 

Conclusion: In HIV-infected patients, ART rapidly reduced levels of key mediators of the innate immune response associated with accelerated aging.  However, IL-6 increased during the same time period suggesting ongoing immune activation that may continue to promote senescence.  Long-term studies are necessary to characterize continuing mechanisms for immune activation among those with treated HIV.

Archana Maniar, M.D., Internal Medicine, Division of Infectious Diseases, UC Davis Medical Center, Sacramento, CA, Erin Hsu, MD, Infectious Diseases, California Pacific Medical Center, San Francisco, CA, Sumathi Sankaran, PhD, Medical Microbiology, University of California, Davis, Davis, CA, David Asmuth, MD, Infectious Diseases, University of California Davis Medical Center, Sacramento, CA and John Rutledge, MD, Department of Internal Medicine; Division of Cardiology, UC Davis Medical Center, Sacramento, CA

Disclosures:

A. Maniar, None

E. Hsu, None

S. Sankaran, None

D. Asmuth, None

J. Rutledge, None

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