Endothelial Dysfunction Is Related to Monocyte Activation in Antiretroviral-Treated People With HIV and HIV-Negative Adults in Kenya

Tecla M Temu; Stephen J Polyak; Jerry S Zifodya; Celestine N Wanjalla; John R Koethe; Sarah Masyuko; Jerusha Nyabiage; John Kinuthia; Ana L Gervassi; Julius Oyugi; Stephanie Page; Carey Farquhar

doi:10.1093/ofid/ofaa425

Endothelial Dysfunction Is Related to Monocyte Activation in Antiretroviral-Treated People With HIV and HIV-Negative Adults in Kenya

Open Forum Infect Dis. 2020 Sep 12;7(10):ofaa425. doi: 10.1093/ofid/ofaa425. eCollection 2020 Oct.

Authors

Affiliations

¹ Department of Global Health, University of Washington, Seattle, Washington, USA.
² Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
³ Department of Medicine, Tulane University, New Orleans, Louisiana, USA.
⁴ Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
⁵ Kenyatta National Hospital, Nairobi, Kenya.
⁶ Center for Infectious Disease Research, Seattle Biomedical Research Institute, Seattle, Washington, USA.
⁷ Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
⁸ Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington, USA.

Abstract

Background: Residual monocyte activation may contribute to increased risk for endothelial dysfunction and subsequent atherosclerotic cardiovascular diseases (CVDs) among people with HIV (PWH) on antiretroviral therapy (ART). We examined the relationship between monocyte activation and endothelial activation in PWH in Kenya.

Methods: Serum levels of markers of endothelial activation (soluble/circulating intercellular [sICAM-1] and vascular [sVCAM-1] cell adhesion molecule-1), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and monocyte activation (soluble CD14 [sCD14]) were measured in 275 PWH on ART and 266 HIV-negative persons. Linear regression was used to evaluate associations, adjusting for demographic and traditional CVD risk factors.

Results: Among 541 participants, the median age was 43 years, 50% were female, and most PWH were virally suppressed (97%). sICAM-1 and sVCAM-1 levels were significantly higher in PWH than in HIV-negative participants (P < .001 for both). After further adjustment for traditional CVD risk factors, HIV infection remained associated with 49% (95% CI, 33% to 67%) greater sICAM-1 and 30% (95% CI, 14% to 48%) greater sVCAM-1 relative to uninfected controls. Adjustment for sCD14 substantially attenuated the difference between PWH and HIV-negative individuals. In a stratified analysis of PWH, both sICAM-1 and sVCAM-1 were positively associated with sCD14 (P < .001).

Conclusions: Despite viral suppression, African PWH have evidence of enhanced endothelial activation associated with sCD14, suggesting that monocyte activation plays a role in atherosclerotic plaque development. Future studies are needed to determine mechanistic pathways leading to monocyte activation in this population.

Keywords: Africa; HIV; I-FABP; antiretroviral therapy; endothelial activation; inflammation; sCD14.

Abstract

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