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HIV-related arterial stiffness in Malawian adults is associated with proportion of PD-1 expressing CD8 T-cells and reverses with anti-retroviral therapy

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Kelly, Christine, Mwandumba, Henry C, Heyderman, Robert S, Jambo, Kondwani, Kamng’ona, Raphael, Chammudzi, Mishek, Sheha, Irene, Peterson, Ingrid, Rapala, Alicja, Mallewa, Jane, Walker, A Sarah, Klein, Nigel and Khoo, Saye (2019) 'HIV-related arterial stiffness in Malawian adults is associated with proportion of PD-1 expressing CD8 T-cells and reverses with anti-retroviral therapy'. Journal of Infectious Disease. (In Press)

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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
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 568 Cellular immunity. Immunologic cytotoxicity. Immunocompetence. Immunologic factors (General)
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.2 Therapy
WG Cardiovascular System > WG 100 General works
Faculty: Department: Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI): https://doi.org/10.1093/infdis/jiz015
Depositing User: Stacy Murtagh
Date Deposited: 18 Jan 2019 14:08
Last Modified: 11 Apr 2019 09:34
URI: http://archive.lstmed.ac.uk/id/eprint/9970

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