HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1–Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy



Kelly, Christine, Mwandumba, Henry C, Heyderman, Robert S, Jambo, Kondwani ORCID: 0000-0002-3195-2210, Kamng'ona, Raphael, Chammudzi, Mishek, Sheha, Irene, Peterson, Ingrid, Rapala, Alicja, Mallewa, Jane
et al (show 3 more authors) (2019) HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1–Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy. The Journal of infectious diseases, 219 (12). pp. 1948-1958.

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Abstract

Background:The contribution of immune activation to arterial stiffness and its reversibility in HIV-infected adults in sub-Saharan Africa is unknown. Methods:HIV-uninfected and HIV-infected Malawian adults initiating antiretroviral therapy (ART) with CD4 <100 cells/l were enrolled (2-weeks post-ART for HIV-infected) and followed for 44-weeks. We evaluated the relationship between carotid femoral pulse wave velocity (cfPWV) and T-cell activation (HLADR+CD38+), exhaustion (PD1+) and senescence (CD57+), and monocyte subsets using normal regression. Results:In 279 HIV-infected and 110 HIV-uninfected adults, 142(37%) had hypertension. HIV was independently associated with 12% higher cfPWV (p=0.02) at baseline, and week-10 (14% higher, p=0.02) but resolved by week-22. CD4 and CD8 T-cell exhaustion(PD1+) were independently associated with higher cfPWV at baseline (p=0.02). At 44-weeks, arterial stiffness improved more in those with greater decreases in %CD8 and %CD8PD1+ T-cells (p=0.01, p=0.03 respectively). When considering HIV-infected participants alone, adjusted arterial stiffness at week-44 tended to be lower in those with higher baseline %CD8PD1+ T-cells (p=0.054). Conclusions:PD-1+ expressing CD8 T-cells are associated with HIV-related arterial stiffness, which remains elevated during the first three months on ART. Resources to prevent cardiovascular disease in sub-Saharan Africa should focus on blood pressure reduction, and those with low CD4 during early ART.

Item Type: Article
Uncontrolled Keywords: HIV, PD-1, T-cell exhaustion, sub-Saharan Africa, endothelial damage, arterial stiffness, cardiovascular disease
Depositing User: Symplectic Admin
Date Deposited: 05 Feb 2019 10:16
Last Modified: 19 Jan 2023 01:05
DOI: 10.1093/infdis/jiz015
Open Access URL: https://doi.org/10.1093/infdis/jiz015
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3032282