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Is low-level HIV-1 viraemia associated with elevated levels of markers of immune activation, coagulation and cardiovascular disease?

Elvstam, O. LU ; Medstrand, P. LU ; Jansson, M. LU ; Isberg, P. E. LU ; Gisslén, M. and Björkman, P. LU (2019) In HIV Medicine
Abstract

Objectives: The clinical significance of low-level viraemia (LLV) during antiretroviral therapy (ART) is debated. We retrospectively investigated longitudinal levels of plasma markers associated with inflammation, altered coagulation and cardiovascular disease in Swedish HIV-positive adults in relation to LLV or permanent virological suppression during long-term ART. Methods: Plasma levels of C-reactive protein (CRP), D-dimer, vascular cell adhesion molecule 1 (VCAM-1), suppression of tumorigenicity 2 (ST2), growth differentiation factor 15 (GDF-15), soluble CD14 (sCD14), soluble CD163 (sCD163), interferon-γ-induced protein 10 (IP-10) and β-2-microglobulin were measured in 34 individuals with LLV (viral load 50–999 HIV-1 RNA copies/mL)... (More)

Objectives: The clinical significance of low-level viraemia (LLV) during antiretroviral therapy (ART) is debated. We retrospectively investigated longitudinal levels of plasma markers associated with inflammation, altered coagulation and cardiovascular disease in Swedish HIV-positive adults in relation to LLV or permanent virological suppression during long-term ART. Methods: Plasma levels of C-reactive protein (CRP), D-dimer, vascular cell adhesion molecule 1 (VCAM-1), suppression of tumorigenicity 2 (ST2), growth differentiation factor 15 (GDF-15), soluble CD14 (sCD14), soluble CD163 (sCD163), interferon-γ-induced protein 10 (IP-10) and β-2-microglobulin were measured in 34 individuals with LLV (viral load 50–999 HIV-1 RNA copies/mL) and in matched controls with persistent virological suppression. Biomarker levels were analysed in samples obtained during episodes of LLV and follow-up samples obtained 1 year later (with similar timing for controls). All biomarkers were analysed using an independent sample t-test and analysis of covariance (ANCOVA) after logarithmic transformation. Log-rank analysis was applied for markers with concentration values out of range. Results: Compared with controls, patients with LLV had significantly higher levels of GDF-15 [geometric mean 3416 (95% confidence interval (CI) 804–14 516) pg/mL versus 2002 (95% CI 355–11 295) pg/mL in controls; P = 0.026] and D-dimer [mean 1114 (95% CI 125–9917) ng/mL versus 756 (95% CI 157–3626) ng/mL; P = 0.038] after adjustment for age, CD4 count nadir and type of ART. In the unadjusted t-test, only GDF-15 was significantly higher and in the log-rank test, both GDF-15 and D-dimer were significantly elevated. No significant differences were observed for the other biomarkers analysed. Conclusions: Although levels of inflammation markers were similar in ART recipients with and without LLV, persons with LLV had significantly higher levels of GDF-15 and D-dimer. These findings suggest a potential link between LLV and cardiovascular outcomes.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
cardiovascular disease, coagulation, HIV, inflammation, low-level viraemia
in
HIV Medicine
publisher
Wiley-Blackwell
external identifiers
  • scopus:85066615974
ISSN
1464-2662
DOI
10.1111/hiv.12756
language
English
LU publication?
yes
id
27c9b1cb-d6a3-4e61-8547-4736273c32d2
date added to LUP
2019-06-17 19:28:43
date last changed
2019-07-09 04:48:24
@article{27c9b1cb-d6a3-4e61-8547-4736273c32d2,
  abstract     = {<p>Objectives: The clinical significance of low-level viraemia (LLV) during antiretroviral therapy (ART) is debated. We retrospectively investigated longitudinal levels of plasma markers associated with inflammation, altered coagulation and cardiovascular disease in Swedish HIV-positive adults in relation to LLV or permanent virological suppression during long-term ART. Methods: Plasma levels of C-reactive protein (CRP), D-dimer, vascular cell adhesion molecule 1 (VCAM-1), suppression of tumorigenicity 2 (ST2), growth differentiation factor 15 (GDF-15), soluble CD14 (sCD14), soluble CD163 (sCD163), interferon-γ-induced protein 10 (IP-10) and β-2-microglobulin were measured in 34 individuals with LLV (viral load 50–999 HIV-1 RNA copies/mL) and in matched controls with persistent virological suppression. Biomarker levels were analysed in samples obtained during episodes of LLV and follow-up samples obtained 1 year later (with similar timing for controls). All biomarkers were analysed using an independent sample t-test and analysis of covariance (ANCOVA) after logarithmic transformation. Log-rank analysis was applied for markers with concentration values out of range. Results: Compared with controls, patients with LLV had significantly higher levels of GDF-15 [geometric mean 3416 (95% confidence interval (CI) 804–14 516) pg/mL versus 2002 (95% CI 355–11 295) pg/mL in controls; P = 0.026] and D-dimer [mean 1114 (95% CI 125–9917) ng/mL versus 756 (95% CI 157–3626) ng/mL; P = 0.038] after adjustment for age, CD4 count nadir and type of ART. In the unadjusted t-test, only GDF-15 was significantly higher and in the log-rank test, both GDF-15 and D-dimer were significantly elevated. No significant differences were observed for the other biomarkers analysed. Conclusions: Although levels of inflammation markers were similar in ART recipients with and without LLV, persons with LLV had significantly higher levels of GDF-15 and D-dimer. These findings suggest a potential link between LLV and cardiovascular outcomes.</p>},
  author       = {Elvstam, O. and Medstrand, P. and Jansson, M. and Isberg, P. E. and Gisslén, M. and Björkman, P.},
  issn         = {1464-2662},
  keyword      = {cardiovascular disease,coagulation,HIV,inflammation,low-level viraemia},
  language     = {eng},
  month        = {05},
  publisher    = {Wiley-Blackwell},
  series       = {HIV Medicine},
  title        = {Is low-level HIV-1 viraemia associated with elevated levels of markers of immune activation, coagulation and cardiovascular disease?},
  url          = {http://dx.doi.org/10.1111/hiv.12756},
  year         = {2019},
}