Clinical, behavioral and biomarker predictors of PCSK9 levels in HIV-infected patients naïve of statin therapy: A cross-sectional analysis from the Swiss HIV cohort

Background and aims: Better characterization of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) profile is currently needed to tailor appropriate lipid-lowering strategies in HIV patients. Methods: HIV-infected individuals aged ≥ 40 years and naive of statin therapy included in the Swiss HIV cohort study were screened for PCSK9 levels with a routine blood sample collection in 2014 at the Geneva University Hospitals. An exploratory linear regression model was built including clinical (age, sex, ethnicity, cardiovascular risk factors, body mass index, low CD4 defined as ≤200 cells/μl, leucocytes, lymphocytes, platelet, antiretroviral therapy), behavioral (tobacco and marijuana smoking, alcohol use and physical activity) and biomarker (CRP, TNF-α, IL-8, Il-10 and MCP-1) to investigate association with continuous PCSK9 levels. Results: We studied 239 HIV-infected individuals who met inclusion criteria and available PCSK9 levels with a mean age of 49 years. 35 subjects (14.6%) reported marijuana consumption, of whom 20 (57.1%) reported daily consumption and 15 (6.3%) occasional use. PCSK9 levels were correlated with low-density lipoprotein-cholesterol (LDL-C). Our exploratory model identified marijuana consumption (p=0.023) and low CD4 values (p=0.020) as significantly associated factors with higher PCSK9 levels. No association was found with Framingham risk score. Patients with marijuana consumption had significantly higher levels of PCSK9 with a dose-response effect (p < 0.001); the association persisted after adjustment for the calculated Framingham risk score (p=0.003) and additional adjustment for clinical variables (p=0.027). Conclusions: In HIV-infected individuals naïve of statin treatment, marijuana consumption and low CD4 values are associated with higher PCSK9 levels independently of clinically relevant confounding factors.