Association of hepatitis C with markers of hemostasis in HIV-infected and uninfected women in the women's interagency HIV study (WIHS)

Abstract

Background: Coinfection with HIV and hepatitis C virus (HCV) is common. HIV infection and treatment are associated with hypercoagulability; thrombosis in HCV is underinvestigated. Proposed markers of hemostasis in HIV include higher D-dimer, Factor VIII%, and plasminogen activator inhibitor-1 (PAI-1) antigen and lower total Protein S% (TPS) but have not been examined in HCV. We assessed the independent association of HCV with these 4 measures of hemostasis in a multicenter, prospective study of HIV: the Women's Interagency HIV Study.

Methods: We randomly selected 450 HCV-infected (anti-HCV+ with detectable plasma HCV RNA) and 450 HCV-uninfected (anti-HCV-) women. HCV was the main exposure of interest in regression models.

Results: Four hundred forty-three HCV+ and 425 HCV- women were included. HCV+ women had higher Factor VIII% (124.4% ± 3.9% vs. 101.8% ± 3.7%, P < 0.001) and lower TPS (75.7% ± 1.1% vs. 84.3% ± 1.1%, <0.001) than HCV- women, independent of HIV infection and viral load; there was little difference in PAI-1 or log10 D-dimer. After adjustment for confounders, these inferences remained. HIV infection was independently associated with higher Factor VIII% and log10 D-dimer and lower TPS.

Conclusions: HCV was independently associated with higher Factor VIII% and lower TPS consistent with hypercoagulability. Higher Factor VIII% and D-dimer and lower TPS were also strongly associated with HIV infection and levels of HIV viremia, independent of HCV infection. Further investigation is needed to determine if there is increased thrombotic risk from HCV. Studies examining hemostasis markers in HIV infection must also assess the contribution of HCV infection.

Figure 1. Factor VIII % by HCV and HIV Viral Load

* Population margins adjusted for WIHS site and test date; SEM: standard error of the mean; VL: Viral Load; Error bars indicate SEM. Low VL: 0 – 4000 copies/mL, Medium VL: 4001 – 55000 copies/mL, high VL: > 55000 copies/mL. P-value above each HIV group compares HCV-negative vs. HCV-positive in each HIV group; P-value for the trend of HIV – to High VL, p<0.0001.

Figure 2. Total Protein S% by HCV and HIV Viral Load

* Population margins adjusted for WIHS site and test date; SEM: standard error of the mean; VL: Viral Load; Error bars indicate SEM. Low VL: 0 – 4000 copies/mL, Medium VL: 4001 – 55000 copies/mL, high VL: > 55000 copies/mL. P-value above each HIV group compares HCV-negative vs. HCV-positive in each HIV group; P-value for the trend of HIV – to High VL (adjusted for HCV),, p<0.0001.