931 
The Effect of Hepatitis C Infection on Metabolic Parameters following Initial Therapy of HIV-infected Subjects with Nucleoside +/- NNRTI Regimens
Cecilia Shikuma*1, H Ribaudo2, E Zheng2, M Glesby3, W Meyer4, K Tashima5, B Bastow6, D Kuritzkes7, R Gulick3, and AIDS Clinical Trials Group A5095 Study Team
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, Silver Spring, MD, US; and 7Brigham and Women`s Hosp, Boston, MA, US
Background: Limited
information is available on the effect of hepatitis C (HCV) co-infection on
metabolic changes in HIV subjects starting initial nucleoside ± NNRTI ART. We
assessed fasting metabolic parameters in subjects with and without HCV antibody
following initiation of such therapy in an AIDS Clinical Trials Group clinical
trial.
Methods: Analyses involved
78 HCV + and 760 HCV– subjects in A5095, a study of
initial treatment of HIV infection with a triple-nucleoside (zidoudine [ZDV]/lamivudine
[3TC]/abacavir [ABC]), 3-drug efavirenz (EFV) [ZDV/3TC+EFV], or 4-drug EFV
[ZDV/3TC/ABC+EFV] regimen. Fasting metabolic parameters (total, HDL, and LDL
cholesterol [C], lactate, triglyceride [TG], glucose, and insulin with
calculation of HOMA-IR) were assessed at week 0, 24, and 96. The distribution
of metabolic parameters at each week and their changes from baseline (week 0 to
24 and week 0 to 96) were compared by Wilcoxon test between HCV+ and
HCV– subjects.
Results: At
baseline, all metabolic parameters were similar except for slightly higher TG
in HCV+ subjects (HCV+ vs HCV–[median]: 135
vs 122 mg/dL, p = 0.04). Numbers
of HCV+ subjects were equal across arms. Following therapy, HOMA-IR
levels were modestly higher and LDL-C levels were modestly lower in the HCV+
compared to HCV- subjects at both week 24 (HCV+ vs HCV–
[median]: HOMA-IR 2.41 vs 1.92, p
= 0.03; LDL-C 95 vs 108 mg/dL, p =
0.002), and week 96 (HCV+ vs HCV– [median]: HOMA-IR 2.89
vs 2.16, p = 0.017; LDL-C 98 vs
113 mg/dL, p = 0.012). Rates of
diabetes (fasting glucose ≥126 mg/dL) were similar at baseline; however
at week 96, a greater proportion of HCV+ compared to HCV–
subjects had diabetes (9% vs 3%, p
= 0.03). While differences were modest, changes from week 0 to 24 showed
greater increases in HDL-C and in HOMA-IR and smaller increases in LDL-C and TG
in HCV+ compared to HCV– subjects (all p <0.05); similar
trends were apparent in the week 0 to 96 changes but only HDL-C remained statistically
significant (p = 0.02). No
differences in lactates were found either in distribution at the assessed time-points
or in change over time.
Conclusions: HCV
co-infection modestly alters some metabolic parameters following NRTI ± NNRTI
ART. In particular, HCV co-infection results in higher insulin resistance and
rates of diabetes, and lower LDL-C values. The cardiovascular impact of these
differences remains to be determined.
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