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Inflammatory Markers among Abacavir and non-Abacavir Recipients in the Womens’ Interagency HIV Study and the Multicenter AIDS Cohort Study
Frank Palella*1, S Gange2, R Elion3, L Benning2, R Kaplan4, C WIllliams5, A Landay6, L Jacobson2, and R Tracy7
1Feinberg Sch of Med, Northwestern Univ, Chicago, IL, US; 2Johns Hopkins Univ, Baltimore, MD, US; 3Whitman Walker Clinic, Washington, DC, US; 4Albert Einstein Coll of Med, New York, NY, US; 5NIAID, NIH, Bethesda, MD, US; 6Rush Univ, Chicago, IL, US; and 7Univ of Vermont, Burlington, US
Background: Use of abacavir (ABC) has been associated with increases in
cardiovascular disease and markers of inflammation. Further evaluation of ABC
use and inflammation is needed.
Methods: We identified Multicenter AIDS Cohort Study (MACS)
men and Womens’ Interagency HIV
Study (WIHS) women who initiated ABC either at or
after first HAART initiation while under follow-up. Propensity score methods
were used to identify ABC-unexposed person-visits matched by race/ethnicity,
age, calendar time, smoking, body mass index, HDL, HCV serostatus, pre-HAART
ART use, duration and consistency of HAART use, CD4, and HIV RNA levels. High-sensitivity
C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer
levels were measured at the pre-HAART visit (baseline) and at the on-HAART
index visit defined as the first visit at which ABC use
was reported (exposed) or a matched visit without ABC use (unexposed). Since visits were semi-annual, onset of
ABC use could be <1 to 6 months before the study visit. Random-effects
models were used to compare log-transformed markers and changes from pre-HAART levels in ABC and non-ABC initiators.
Results: We
measured hsCRP and D-dimer levels in 326 matched pairs (197 women; 129 men) and IL-6 levels in
290 matched pairs (194 women; 96
men). In unadjusted models, ABC users at the index
visit had 7% lower mean D-dimer levels (0.26 vs 0.28 mg/mL, p = 0.40), 8% higher hsCRP (1.69 vs 1.56 mg/mL,
p = 0.41), and 1% higher IL-6 (2.20 vs 2.17
pg/mL, p
= 0.90) than non-ABC users. In multivariate models, differences at index visit
between ABC exposed and unexposed were: –3% for D-dimer (p
= 0.66), +2% for hsCRP (p = 0.80), and –5% for IL-6 (p
= 0.58). In this model women
had lower mean D-dimer levels (–5% difference, p = 0.70),
significantly lower hsCRP levels (–33%, p = 0.01), and significantly lower IL-6 levels (–38%,
p = 0.001)
than men. Comparisons of baseline and index visits (mean 4.2 years apart) revealed decreases in D-dimer (p <0.001) and
IL-6 (p
= 0.08) and increases in hsCRP
levels (p <0.001). However, the
changes in markers between visits were
not significantly different
when comparing ABC exposed and unexposed persons (D-dimer p = 0.82, hsCRP
p = 0.64, and IL-6 p
= 0.47).
Conclusions: ABC use was not independently associated with elevated
plasma levels of hsCRP, IL-6, and D-dimer. While changes in the levels of these markers were seen between
the baseline and index visits (D-dimer and IL-6 decreases, hsCRP increases),
they were comparable among persons who initiated ABC versus non-ABC containing HAART.
Women had higher D-dimer and lower CRP levels than men.
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