UCLA

Background: Hepatitis C (HCV) may increase cardiovascular disease (CVD) risk in HIV-infected persons. We hypothesized that HCV virologic clearance reduces CVD risk, as manifested by reduction in non-hepatic CVD biomarkers.

Methods: Of 54 HIV/HCV coinfected subjects who received 72 weeks of pegylated interferon/ribavirin, 27 with and 27 without sustained virologic response (SVR) matched by race/ethnicity and sex, stored serum/plasma before treatment and 24 weeks after end of treatment (EOT) were tested for non-hepatic (sICAM-1, sP-selectin, IL-6, D-dimer, and lipoprotein-associated phospholipase A2 [Lp-PLA2]) and hepatic markers of CVD (cholesterol and hsCRP). Baseline characteristics and biomarkers were compared between SVRs and non-SVRs by Wilcoxon rank sum test. Changes in each biomarker were examined within SVRs/non-SVRs and between groups by t-tests and regression models.

Results: The cohort included 54 subjects, 30 white, 24 black, and 44 male. Baseline levels of non-hepatic markers were not significantly different between groups, including sICAM-1 (overall median [Q1, Q3]=439.2 [365.6, 592.8] ng/mL), sP-selectin (146.7 [94.1, 209.9] ng/mL) and IL-6 (2.32 [1.61, 3.49] pg/mL). Of 52 subjects with baseline Lp-PLA2, 37 (71%) had Lp-PLA2>235 ng/mL. SVRs had a significant decrease in log10 sICAM-1, but not non-SVRs (mean [sd] = -0.09 [0.13] vs -0.01 [0.14], p=0.047 for between group comparison). Adjusting for baseline AST and ALT, SVR was significantly associated with decrease in sICAM-1 (p=0.033), but not after adjusting for change in ALT (p=0.105). At 24 weeks after EOT, 17 (63%) SVRs had Lp-PLA2>235 ng/mL compared to 25 (93%) non-SVRs (p=0.021).

Conclusions: High baseline levels of non-hepatic CVD markers suggest high CVD risk in HIV/HCV coinfection. SVR was associated with decrease in sICAM-1 and lower CVD risk by Lp-PLA2 level. HCV virologic clearance may lower CVD risk through reduction in hepatic, and subsequently systemic, inflammation.