Subsets of CD4 T Cells May Be Markers for Cardiovascular Disease Risk in HIV

Analysis of CD4+ T-cell subsets may help in predicting the risk for cardiovascular disease in patients with HIV infection.

Among patients with HIV infection, T helper type (Th) cells, T effector memory cells re-expressing CD45RA (TERMA), and senescent cells may be markers for incident cardiovascular disease (CVD), according to results of a study published in the Journal of the American College of Cardiology.

Researchers at Vanderbilt University Medical Center in Tennessee sourced data for this analysis from the Veterans Aging Cohort Study (VACS), which was a prospective, observational, longitudinal cohort study. For this analysis, individuals with (n=1270) and without (n=590) HIV infection were age-, gender-, ethnicity-, and location-matched, and blood biomarkers from peripheral blood mononuclear cell samples obtained between 2005 and 2007 were evaluated to assess for associations between T-cell subsets and incident CVD risk through 2016.

Among patients with and without HIV infection included in the analysis, the median age was 51.4 (IQR, 46.3-57.0) and 52.1 (IQR, 46.8-56.6) years, 96.9% and 88.0% were men, 68.7% and 69.8% were Black, 15.8% and 42.9% had a BMI of more than 30 kg/m2, and 16.1% and 24.6% had diabetes, respectively.

Of patients with HIV infection, CD4+ counts of more than 500, between 200 and 500, and less than 200 cells/mm3 were noted in 452, 585, and 232 patients, respectively. The majority (n=1075) of these patients were receiving antiretroviral therapy (ART), specifically nucleoside reverse transcriptase inhibitors (82.5%), non-nucleoside reverse transcriptase inhibitors (35.5%), and protease inhibitors (52.2%).

Compared with patients without HIV infection, HIV-positive patients had higher levels of Th1, Th2, Th17, TERMA, regulatory T (Treg), and senescent cells. For HIV-positive patients only, the researchers found that the number of T cells significantly increased as CD4+ cell counts declined (all P <.01), with the exception of Th1 cells (P =.06).

During a median follow-up period of 9.8 years, 344 incident CVD events occurred, in which the incidence rates were 19.9 and 23.7 per 1000 person-years among the HIV-positive and HIV-negative patients, respectively.

Peripheral circulating CD4 T cell subsets were significantly associated with incident CVD, including both heart failure and atherosclerotic CVD, among PWH.

Cox proportional hazards regression analysis was performed after adjustment for traditional and nontraditional CVD risk factors. Among all patients, the risk for incident CVD significantly increased with every SD increment increase in Th17 (hazard ratio [HR], 1.20; 95% CI, 1.09-1.33; P <.001), TERMA (HR, 1.16; 95% CI, 1.04-1.29; P <.001), senescent (HR, 1.14; 95% CI, 1.02-1.28; P =.02), and Th1 (HR, 1.12; 95% CI, 1.01-1.24; P =.04) CD4+ T cells.

Similar results were observed for incident CVD risk between patients with vs without HIV infection after stratification by HIV status.

Study limitations include potentially limited generalizability, and the use of cryopreserved cells instead of fresh samples.

Based on these results, “Peripheral circulating CD4 T cell subsets were significantly associated with incident CVD, including both heart failure and atherosclerotic CVD, among PWH [patients with HIV infection],” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.


Kundu S, Freiberg MS, Tracy RP, et al. Circulating T cells and cardiovascular risk in people with and without HIV infection. J Am Coll Cardiol. 2022;80(17):1633-1644. doi:10.1016/j.jacc.2022.08.756