Impact of protease inhibitors on circulating PCSK9 levels in HIV-infected antiretroviral-naive patients from an ongoing prospective cohort

Franck Boccara (1) , Mathilde Ghislain (2) , Laurence Meyer (2) , Cecile Goujard (2) , Cedric Le May (3) , Corinne Vigouroux (4) , Jean P. Bastard , Soraya Fellahi (5) , Jacqueline Capeau (6) , Ariel Cohen (7) , Bertrand Cariou (3)

1 CHU Saint-Antoine [AP-HP]
2 CESP - Centre de recherche en épidémiologie et santé des populations
3 ITX - ITX - unité de recherche de l'institut du thorax
4 BIRA-IASB - Belgian Institute for Space Aeronomy / Institut d'Aéronomie Spatiale de Belgique
5 CHU Tenon [AP-HP]
6 UMRS893 - Centre de Recherche Saint-Antoine
7 Thrombose, atherothrombose et pharmacologie appliquée

OBJECTIVE: The study aims to assess the association between proprotein convertase subtilisin/kexin type 9 (PCSK9), a major regulator of LDL cholesterol (LDL-C) homeostasis, and HIV-related dyslipidaemia in a cohort of HIV-positive (HIV+) patients under protease inhibitors. METHODS: Plasma PCSK9 levels were measured in 103 HIV+ patients before and after initiating protease inhibitor-based antiretroviral therapy (ART), and in 90 HIV-negative controls matched for age and sex. PCSK9 was measured by ELISA. HIV+ patients who were not virologically suppressed at follow-up or were on lipid-lowering therapy were excluded. RESULTS: In HIV+ (median age 36 years; 77.7% men), PCSK9 levels did not increase after protease inhibitor exposure (median 14 months) (279.5 ng/ml before, 289.6 ng/ml after; P = 0.49) and were significantly elevated versus controls at all timepoints (adjusted P value before and after: \textless0.05). After protease inhibitor initiation, total cholesterol, LDL-C and HDL cholesterol levels increased, but LDL-C remained lower versus controls. At baseline, PCSK9 levels were positively associated with immunodeficiency and the severity of HIV disease [HIV-1 viral load (P = 0.01), CD4 T-cell count \textless200/μl, P = 0.002], stage C HIV disease (P = 0.0002). In protease inhibitor-treated patients, PCSK9 levels were no longer associated with HIV-related factors but with total cholesterol (P = 0.0006), LDL-C (P = 0.01), HDL cholesterol (P = 0.01), triglycerides (P = 0.05) and glycaemia (P = 0.006). CONCLUSION: PSCK9 levels are elevated in HIV+ patients. In ART-naive patients, the relationship between PCSK9 levels and infection severity suggests an effect of HIV disease. After initiating protease inhibitor-containing ART in virologically suppressed patients, PCSK9 levels were associated with dyslipidaemia similar to controls.

Domaines: Sciences du Vivant [q-bio]

Franck Boccara, Mathilde Ghislain, Laurence Meyer, Cecile Goujard, Cedric Le May, et al.. Impact of protease inhibitors on circulating PCSK9 levels in HIV-infected antiretroviral-naive patients from an ongoing prospective cohort. AIDS. Official journal of the international AIDS Society, 2017, Equipe IV, 31 (17), pp.2367--2376. ⟨10.1097/QAD.0000000000001633⟩. ⟨hal-01832935⟩