title: HIV and Hepatitis C-Coinfected Patients Have Lower Low-Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent "PCSK9-Lipid Paradox".
abstract: Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and improve outcomes in the general population. HIV-infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus (HCV) coinfection, making PCSK9 inhibition a potentially attractive therapy.
  
  
  
  We studied 567 participants from a clinic-based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL-C level was 100 mg/dL (IQR 77-124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol, LDL-C, and high-density lipoprotein cholesterol levels were lower in coinfected patients compared with controls (P<0.001). PCSK9 was 21% higher in HIV/HCV-coinfected patients versus controls (95% CI 9-34%, P<0.001) and 11% higher in coinfected individuals versus those with HIV infection alone (95% CI 3-20%, P=0.008). After adjustment for cardiovascular risk factors, HIV/HCV coinfection remained significantly associated with 20% higher PCSK9 levels versus controls (95% CI 8-33%, P=0.001). Interleukin-6 levels increased in a stepwise fashion from controls (lowest) to HIV-infected to HIV/HCV-coinfected individuals (highest) and correlated with PCSK9 (r=0.11, P=0.018).
  
  
  
  Despite having lower LDL-C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin-6. Clinical trials should be conducted to determine the efficacy of targeted PCSK9 inhibition in the setting of HIV/HCV coinfection.
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA payal.kohli.md@gmail.com.
authors.forename: Payal
authors.initials: P
authors.lastname: Kohli
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA.
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.affiliation: Department of Medicine UCSF, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Medicine UCSF, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Hur
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Weigel
authors.affiliation: Department of Medicine UCSF, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA.
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
authors.affiliation: The Positive Health Program, San Francisco General Hospital, San Francisco, CA.
authors.forename: Steven
authors.initials: S
authors.lastname: Deeks
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: Scott
authors.initials: S
authors.lastname: Wasserman
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: Rob
authors.initials: R
authors.lastname: Scott
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA.
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hsue
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D060085:Coinfection; D050171:Dyslipidemias / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9 / Q000097:blood*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508600:IL6 protein, human; D015850:Interleukin-6; D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: HIV; hepatitis C virus; low‐density lipoprotein cholesterol; proprotein convertase subtilisin kexin 9