20th International AIDS Conference - Melbourne, Australia

Abstract

WEPE006 - Poster Exhibition


Peripheral blood mononuclear cell oxidative phosphorylation complex i activity levels are decreased by HIV and correlate with extent of immune dysregulation and activation

C.M. Shikuma1, L.C. Ndhlovu1, D. Chow1, L.-M. Gangcuangco1, S.M. Keating2,3, P.J. Norris2,3, K. Kallianpur1, B. Nakamoto1,4, T. Umaki1, J.D. Barbour1, M. Gerschenson5

1University of Hawaii, Hawaii Center for AIDS, Honolulu, United States, 2Blood Systems Research Institute, San Francisco, United States, 3University of California, San Francisco, United States, 4Straub Medical Center, Honolulu, United States, 5University of Hawaii John A. Burns School of Medicine, Cell and Molecular Biology, Honolulu, United States

Background: A close relationship exists between energy metabolism and chronic inflammation. Little is known about changes in oxidative phosphorylation (OXPHOS) in the context of HIV and whether alterations are influenced by HIV immune dysregulation and/or inflammation.
Methods: Cross-sectional analysis of entry data from a cohort study of HIV-infected and HIV sero-negative subjects age ≥ 40 years. HIV-infected subjects were on stable antiretroviral therapy
≥ 6 months. Peripheral blood mononuclear cells (PBMC) were assayed for OXPHOS Complex 1
(CI, NADH dehydrogenase) and Complex IV (CIV, cytochrome c oxidase) enzyme activities by ELISA (Abcam). Plasma biomarkers sE selectin, sVCAM-1, sICAM-1, MMP-9, MPO, tPAI-1, CRP, SAA, SAP, IL-1β, IL-6, IL-8, IL-10, TNF-α, MCP-1, VEGF, IFN-γ, and NT ProBNP were assessed using a Milliplex Human Cardiovascular Disease panel (EMD Millipore) by Luminex technology. Spearman correlation and linear regression were used for analyses.
Results: Analyses involved 149 HIV+ and 44 HIV sero-negative subjects. There were no differences between groups by gender (87% male), age [mean (SD)] 52.4 (7.8) yrs, or ethnicity (58.6% Caucasian). HIV+ subjects had CD4 T cell count /percent of 520.5(249.8) /29.4(11.2)%, and HIV RNA was ≤ 50 copies/ml in 84.6%. HIV+ patients had lower PBMC CI activities than HIV sero-negative controls [mean (SD): 68.6 (27) vs 156.6 (22) optical density/µgx103, p< 0.001]. No difference was found in CIV activity. Among HIV+ subjects, CI activity correlated positively with CD4% (rho=0.185, p=0.02) (see figure).

Relationship of CD4 percent and OXPHOS CI activity
[Relationship of CD4 percent and OXPHOS CI activity]

In multivariate analyses, CD4% predicted CI activity (β=0.54, p=0.009) independently of age, gender and ethnicity. CI activity correlated negatively with multiple cytokines: sVCAM, MPO, CRP, SAA, SAP, IL-1β, and MCP-1 (all p< 0.01).
Conclusions: OXPHOS CI activity levels in PBMC are lower in HIV infected individuals and decrease with increasing immune dysregulation as assessed by CD4 percent. Decrease in CI activity correlate with higher levels of multiple pro-inflammatory cytokines.


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