A pharmacogenetic study in HIV-infected patients treated with ritonavir: hematological and cardiovascular disease risk analysis

BACKGROUND: Ritonavir (RTV), a drug used in patients with human immunodeficiency virus (HIV), could cause lipodystrophy and cardiovascular diseases (CVD). HIV-infected patients could have accelerated atherogenesis, per se, depending on genetics. Aim of this study was to analyze the influence of polymorphisms in genes associated with lipids and RTV transport and metabolism, in predicting metabolic and cardiovascular biomarkers in a cohort of HIV-infected patients.METHODS: Genotypes were assessed through real-time polymerase chain reaction (PCR), whereas CVD risk calculating the ratio of total cholesterol (TC) and high density lipoproteins (HDL), considering a value >5 as higher risk.RESULTS : Ninety-nine patients were enrolled. Low density lipoprotein (LDL), HDL, TC and triglycerides (TG) increased over time, other than CD4+ cell count and percentage, WBC, transaminases, gamma-glutamyl transferase (GGT) and pancreatic amylase; only GGT remained constant. Concomitant drug administration influencing on week 48 TC/HDL ratio >5 was evaluated: a statistical significance was showed for lopinavir, darunavir and atazanavir. ABCB1 2677 GG/GT and aspartate aminotransferase >40 U/L at baseline, whereas age >50 years, ABCC2-24 GG and GGT<71 U/L at 48 weeks predicted TC/HDL ratio >5.CONCLUSIONS: This was the first work showing that RTV and lipid-related polymorphisms (ABCB1 2677 and ABCC2-24) are able to affect blood-related markers and TC/HDL ratio >5 in a cohort of HIV-affected patients. Further analyses are warranted for cobicistat, in order to compare the data.