title: Inflammatory biomarkers and abacavir use in the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.
abstract: OBJECTIVE
  To assess associations between abacavir (ABC) use and systemic inflammation.
  
  
  METHODS
  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) (microg/ml), interleukin-6 (IL-6) (pg/ml), and D-dimer (microg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. f-palella@northwestern.edu
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Palella
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Lorie
authors.initials: L
authors.lastname: Benning
authors.forename: Lisa
authors.initials: L
authors.lastname: Jacobson
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Richard
authors.initials: R
authors.lastname: Elion
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced*; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D015224:Dideoxynucleosides; D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; D015850:Interleukin-6; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C036309:fibrin fragment D