Inflammatory biomarkers and abacavir use in the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.
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.
Palella
Frank J
FJ
Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. f-palella@northwestern.edu
Gange
Stephen J
SJ
Benning
Lorie
L
Jacobson
Lisa
L
Kaplan
Robert C
RC
Landay
Alan L
AL
Tracy
Russell P
RP
Elion
Richard
R
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
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