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

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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<sup>+</sup> and CD8<sup>+</sup> 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<sup>+</sup>CD38<sup>+</sup>DR+ and CD4<sup>+</sup>CD38<sup>+</sup>DR+. 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<sup>+</sup> and CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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.

Original languageEnglish (US)
Pages (from-to)349-356
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume67
Issue number3
StatePublished - 2014

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Highly Active Antiretroviral Therapy
Carotid Arteries
HIV
T-Lymphocytes
Vascular Stiffness
Atherosclerosis
Hepatitis C
HIV Infections
Linear Models
Elasticity
HLA-DR Antigens
CD4 Lymphocyte Count
Blood Vessels
Longitudinal Studies
Disease Progression
Comorbidity
Flow Cytometry
Cardiovascular Diseases

Keywords

  • Arterial stiffness
  • HIV infection
  • T-cell activation

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Medicine(all)

Cite this

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. / Karim, Roksana; Mack, Wendy J.; Kono, Naoko; Tien, Phyllis C.; Anastos, Kathryn; Lazar, Jason; Young, Mary; Desai, Seema; Golub, Elizabeth T.; Kaplan, Robert C.; Hodis, Howard N.; Kovacs, Andrea.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 67, No. 3, 2014, p. 349-356.

Research output: Contribution to journalArticle

Karim, Roksana ; Mack, Wendy J. ; Kono, Naoko ; Tien, Phyllis C. ; Anastos, Kathryn ; Lazar, Jason ; Young, Mary ; Desai, Seema ; Golub, Elizabeth T. ; Kaplan, Robert C. ; Hodis, Howard N. ; Kovacs, Andrea. / 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. In: Journal of Acquired Immune Deficiency Syndromes. 2014 ; Vol. 67, No. 3. pp. 349-356.
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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+CD38+DR+. 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.",
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T1 - 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

AU - Karim, Roksana

AU - Mack, Wendy J.

AU - Kono, Naoko

AU - Tien, Phyllis C.

AU - Anastos, Kathryn

AU - Lazar, Jason

AU - Young, Mary

AU - Desai, Seema

AU - Golub, Elizabeth T.

AU - Kaplan, Robert C.

AU - Hodis, Howard N.

AU - Kovacs, Andrea

PY - 2014

Y1 - 2014

N2 - 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+CD38+DR+. 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.

AB - 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+CD38+DR+. 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.

KW - Arterial stiffness

KW - HIV infection

KW - T-cell activation

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