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Inflammatory Markers among Abacavir and non-Abacavir Recipients in the Womens' Interagency HIV Study and the Multicenter AIDS Cohort Study
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Reported by Jules Levin
CROI 2009 Montreal Feb 8-12
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
Author Conclusions:
Biomarker level changes were seen between the baseline & index visits (D-dimer and IL-6 decreases, hsCRP increases), and were comparable among persons who initiated ABC vs non-ABC containing HAART. From Jules: of note the biomarker levels as seen in graph below were all with normal ranges suggested by presenter in slide.
ABC use was not indepently associated with elevated plasma levels of hsCRP, IL=6 and d-dimer when compared to levls in non-ABC users.
WIHS women had lower CRP & IL-6 levels than MACS men at index visit.
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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