Inflammatory biomarkers and abacavir use in the women's Interagency HIV study and the multicenter AIDS cohort study

Frank J. Palella, Stephen J. Gange, Lorie Benning, Lisa Jacobson, Robert C. Kaplan, Alan L. Landay, Russell P. Tracy, Richard Elion

Research output: Contribution to journalArticle

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Abstract

Objective: To assess associations between abacavir (ABC) use and systemic inflammation. Design: Nested case-control study. Methods: The Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) cohort participants who initiated ABC were matched, using propensity score methods, to ABC-unexposed persons. Levels of high-sensitivity C-reactive protein (hsCRP) (μg/ml), interleukin-6 (IL-6) (pg/ml), and D-dimer (μg/ml) were measured from pre-HAART and on-HAART plasma. Random-effects models compared markers by ABC exposure and by changes from pre-HAART levels. Results: Biomarkers were measured in N = 508 matched pairs (328 women; 180 men). Pre-HAART levels did not differ by exposure group except that hsCRP levels were higher among WIHS women who subsequently used ABC (P = 0.04). Regardless of ABC use, mean hsCRP increases and D-dimer reductions were seen when comparing pre-HAART to on-HAART levels, in the overall group (28 and-27%), for MACS men (28 and-31%) and for WIHS women [29 and-24%, P < 0.01 for all]; IL-6 levels declined in MACS men (P = 0.02). No adjusted biomarker level differences existed by ABC exposure at the on-HAART visit. HIV RNA reductions correlated with D-dimer (r = 0.14, P < 0.01) and IL-6 (r = 0.12, P < 0.01) reductions. Associations between ABC use and mean biomarker levels were modified by pre-HAART antiretroviral therapy experience. Renal dysfunction was equally likely among non-ABC and ABC recipients. DISCUSSION: ABC use was not associated with plasma elevations in hsCRP, IL-6, and D-dimer. Mechanisms other than increased systemic inflammation may account for ABC's reported association with increased cardiovascular disease. HAART-associated reductions in D-dimer and IL-6 were apparent regardless of ABC use and were correlated with HIV RNA reductions.

Original languageEnglish (US)
Pages (from-to)1657-1665
Number of pages9
JournalAIDS
Volume24
Issue number11
DOIs
StatePublished - Jul 17 2010

Fingerprint

Multicenter Studies
Highly Active Antiretroviral Therapy
Acquired Immunodeficiency Syndrome
Cohort Studies
Biomarkers
HIV
Interleukin-6
C-Reactive Protein
abacavir
RNA
Inflammation
Propensity Score
Case-Control Studies
Cardiovascular Diseases
fibrin fragment D
Kidney

Keywords

  • abacavir
  • cytokines
  • HAART
  • HIV infection
  • inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Inflammatory biomarkers and abacavir use in the women's Interagency HIV study and the multicenter AIDS cohort study. / Palella, Frank J.; Gange, Stephen J.; Benning, Lorie; Jacobson, Lisa; Kaplan, Robert C.; Landay, Alan L.; Tracy, Russell P.; Elion, Richard.

In: AIDS, Vol. 24, No. 11, 17.07.2010, p. 1657-1665.

Research output: Contribution to journalArticle

Palella, FJ, Gange, SJ, Benning, L, Jacobson, L, Kaplan, RC, Landay, AL, Tracy, RP & Elion, R 2010, 'Inflammatory biomarkers and abacavir use in the women's Interagency HIV study and the multicenter AIDS cohort study', AIDS, vol. 24, no. 11, pp. 1657-1665. https://doi.org/10.1097/QAD.0b013e3283389dfa
Palella, Frank J. ; Gange, Stephen J. ; Benning, Lorie ; Jacobson, Lisa ; Kaplan, Robert C. ; Landay, Alan L. ; Tracy, Russell P. ; Elion, Richard. / Inflammatory biomarkers and abacavir use in the women's Interagency HIV study and the multicenter AIDS cohort study. In: AIDS. 2010 ; Vol. 24, No. 11. pp. 1657-1665.
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AU - Gange, Stephen J.

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AU - Jacobson, Lisa

AU - Kaplan, Robert C.

AU - Landay, Alan L.

AU - Tracy, Russell P.

AU - Elion, Richard

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N2 - Objective: To assess associations between abacavir (ABC) use and systemic inflammation. Design: Nested case-control study. Methods: The Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) cohort participants who initiated ABC were matched, using propensity score methods, to ABC-unexposed persons. Levels of high-sensitivity C-reactive protein (hsCRP) (μg/ml), interleukin-6 (IL-6) (pg/ml), and D-dimer (μg/ml) were measured from pre-HAART and on-HAART plasma. Random-effects models compared markers by ABC exposure and by changes from pre-HAART levels. Results: Biomarkers were measured in N = 508 matched pairs (328 women; 180 men). Pre-HAART levels did not differ by exposure group except that hsCRP levels were higher among WIHS women who subsequently used ABC (P = 0.04). Regardless of ABC use, mean hsCRP increases and D-dimer reductions were seen when comparing pre-HAART to on-HAART levels, in the overall group (28 and-27%), for MACS men (28 and-31%) and for WIHS women [29 and-24%, P < 0.01 for all]; IL-6 levels declined in MACS men (P = 0.02). No adjusted biomarker level differences existed by ABC exposure at the on-HAART visit. HIV RNA reductions correlated with D-dimer (r = 0.14, P < 0.01) and IL-6 (r = 0.12, P < 0.01) reductions. Associations between ABC use and mean biomarker levels were modified by pre-HAART antiretroviral therapy experience. Renal dysfunction was equally likely among non-ABC and ABC recipients. DISCUSSION: ABC use was not associated with plasma elevations in hsCRP, IL-6, and D-dimer. Mechanisms other than increased systemic inflammation may account for ABC's reported association with increased cardiovascular disease. HAART-associated reductions in D-dimer and IL-6 were apparent regardless of ABC use and were correlated with HIV RNA reductions.

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