T-cell activation, both pre- and post-HAART levels, correlates with carotid artery stiffness over 6.5 years among HIV-infected women in the WIHS.

Abstract

OBJECTIVE:

T-cell activation is a major pathway driving HIV disease progression. Little is known regarding the impact of T-cell activation on HIV-associated atherosclerosis and cardiovascular disease, a common comorbidity in HIV infection. We hypothesized that T-cell activation will predict vascular stiffness, a measure of subclinical atherosclerosis.

DESIGN:

Linear regression models evaluated the covariate-adjusted association of T-cell activation with vascular stiffness.

METHODS:

CD38 and HLA-DR expression on CD4⁺ and CD8⁺ T cells was assessed by flow cytometry among 59 HIV-negative and 376 HIV-infected (185 hepatitis C coinfected) women in the Women's Interagency HIV Study. T-cell activation was defined by CD8⁺CD38⁺DR+ and CD4⁺CD3⁺8DR+. Multiple activation assessments over 6.5 years were averaged. In 140 women, T-cell activation was measured before and after highly active antiretroviral therapy (HAART) initiation. Carotid artery ultrasounds were completed a median of 6.5 years after last measurement of T-cell activation and carotid artery stiffness including distensibility and elasticity were calculated.

RESULTS:

Percentages of CD4⁺ and CD8⁺ T-cell activation were significantly higher in HIV- infected compared with HIV-negative women. Among HIV-negative women, T-cell activation was not associated with carotid artery stiffness. Among HIV-infected women, higher CD4⁺ T-cell activation levels significantly predicted increased arterial stiffness independent of CD4⁺ cell count and HIV RNA. The association was stronger among HIV/hepatitis C-coinfected women compared with HIV-monoinfected women; however, the difference was not statistically significant (P for interaction >0.05). Pre- and post-HAART levels of CD4⁺ T-cell activation significantly predicted carotid artery stiffness.

CONCLUSIONS:

Persistent T-cell activation, even after HAART initiation, can contribute to structural and/or functional vascular damage accelerating atherogenesis in HIV infection. These results need to be confirmed in a longitudinal prospective study.

• Authors: Roksana Karim, Wendy J Mack, Naoko Kono, Phyllis C Tien, Kathryn Anastos, Jason Lazar, Mary Young, Seema Desai, Elizabeth T Golub, Robert C Kaplan, Howard N Hodis, Andrea Kovacs
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 67 Issue 3 Pg. 349-56 (Nov 01 2014) ISSN: 1944-7884 [Electronic] United States
• PMID: 25314253 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• HLA-DR Antigens
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase 1 (metabolism)
• Adult
• Antiretroviral Therapy, Highly Active
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Carotid Artery Diseases (physiopathology)
• Female
• HIV Infections (complications, drug therapy, immunology, physiopathology)
• HIV Seronegativity (immunology)
• HLA-DR Antigens (metabolism)
• Humans
• Linear Models
• Lymphocyte Activation
• Middle Aged
• Predictive Value of Tests
• Prospective Studies
• Vascular Stiffness