Kelly, C;
Mwandumba, HC;
Heyderman, RS;
Jambo, K;
Kamng'ona, R;
Chammudzi, M;
Sheha, I;
... Khoo, S; + view all
(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.
Journal of Infectious Diseases
, 219
(12)
pp. 1948-1958.
10.1093/infdis/jiz015.
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HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1-Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy.pdf - Published Version Download (272kB) | Preview |
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Abstract
Background: The contribution of immune activation to arterial stiffness and its reversibility in human immunodeficiency virus (HIV)–infected adults in sub-Saharan Africa is unknown. / Methods: HIV-uninfected and HIV-infected Malawian adults initiating antiretroviral therapy (ART) with a CD4+ T-cell count of <100 cells/μL were enrolled and followed for 44 weeks; enrollment of infected adults occurred 2 weeks after ART initiation. We evaluated the relationship between carotid femoral pulse wave velocity (cfPWV) and T-cell activation (defined as HLA-DR+CD38+ T cells), exhaustion (define as PD-1+ T cells), and senescence (defined as CD57+ T cells) 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 a 12% higher cfPWV (P = .02) at baseline and a 14% higher cfPWV at week 10 (P = .02), but the increases resolved by week 22. CD4+ and CD8+ T-cell exhaustion were independently associated with a higher cfPWV at baseline (P = .02). At 44 weeks, arterial stiffness improved more in those with greater decreases in the percentage of CD8+ T cells and the percentage of PD-1+CD8+ T cells (P = .01 and P = .03, respectively). When considering HIV-infected participants alone, the adjusted arterial stiffness at week 44 tended to be lower in those with higher baseline percentage of PD-1+CD8+ T cells (P = .054). / Conclusions: PD-1+CD8+ T-cells are associated with HIV-related arterial stiffness, which remains elevated during the first 3 months of ART. Resources to prevent cardiovascular disease in sub-Saharan Africa should focus on blood pressure reduction and individuals with a low CD4+ T-cell count during early ART.
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