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

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.