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96-Week Effects of Suppressive Efavirenz-containing ART, Abacavir, and Sex on High-sensitivity C-reactive Protein: ACTG A5095
Cecilia Shikuma*1, E Zheng2, H Ribaudo2, J Andersen2, M Glesby3, W Meyer III4, K Tashima5, B Bastow6, D Kuritzkes7, R Gulick3, and AIDS Clinical Trials Group A5095
1Univ of Hawaii, Honolulu, US; 2Harvard Sch of Publ Hlth, Boston, MA, US; 3Weill Med Coll of Cornell Univ, New York, NY, US; 4Quest Diagnostics, Baltimore, MD, US; 5Brown Univ, Providence, RI, US; 6Social & Sci Systems Inc, Silver Spring, MD, US; and 7Brigham and Women`s Hosp, Boston, MA, US
Background: High-sensitivity C-reactive protein (hs-CRP)
levels predict cardiovascular risk and are associated with mortality in HIV-infected
women. Indinavir-based therapy has been reported to
result in stable or decreased hs-CRP levels. No information is available on hs-CRP
changes with NNRTI-based therapy. We assessed the 96-week effects of
efavirenz (EFV) -based therapy with or without abacavir (ABC) on hs-CRP levels
among ARV-naïve patients within the AIDS Clinical Trials Group A5095 trial.
Methods: hs-CRP was assayed in banked baseline and
week-96 sera from 100 participants with HIV RNA <50 copies/mL at study weeks
24 and 96 who were randomized to and remained (through week 96 of study) on 1
of the 2 EFV-containing regimens of A5095: zidovudine (ZDV)/lamivudine (3TC)+EFV
or ZDV/3TC/ABC+EFV. Analyses utilized all women enrolled in A5095 who satisfied
these criteria with sufficient sample volume available (n = 39) and 61 randomly
selected men from n = 346. hs-CRP levels at baseline and changes from week 0 to
96 were compared by sex and randomization arm by Wilcoxon rank sum test. Shifts
in hs-CRP distribution were estimated by the Hodges-Lehmann method.
Associations between week 0 to 96 changes in hs-CRP and week 0 to 96 changes in
CD4 counts and fasting metabolic parameters were examined by Spearman
correlation coefficients.
Results: The median hs-CRP level in the entire
cohort was 2.3 mg/L (Q1 0.9, Q3 4.9) at baseline and not different for men and
women (median 1.6 mg/L vs 2.6 mg/L, p = 0.36). Overall, there was an
increase in hs-CRP from week 0 to 96 (median 1.3, p <0.001, [95%CI
0.7 to 2.7]). A larger increase in hs-CRP was seen for women compared to men
(median 3.7 [95%CI 1.7 to 7.2] mg/L vs 0.5 [–0.3 to 1.3] mg/L, p = 0.001,
shift in center of distribution 3.3 mg/L [95%CI 1.3 to 5.8]). This change was
significant in women (p <0.001) but not in men (p = 0.15). No
significant difference in hs-CRP levels was noted between the arms with (n = 39)
and without ABC (n = 61), at baseline (median 3.2 mg/L vs 2.0 mg/L, p = 0.25)
or change to week 96 (median 1.7 mg/L vs 1.1 mg/L, p = 0.50).
Significant correlations were not detected between changes in hs-CRP and
changes in CD4 count or fasting metabolic measures (p >0.30).
Conclusions: Durably suppressive therapy with
EFV-based regimens did not improve hs-CRP levels over a 96-week period.
Overall, an increase was seen which was greater for women than men. Inclusion
of ABC had no significant effect on changes in hs-CRP levels.
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