Previous studies have demonstrated a link between protease inhibitor (PI)-based therapy and lipid dysregulation. The main objective of this study was to examine whether cocaine use may modify PI-associated dyslipidemia in adults. Between June 2003 and June 2014, 957 human immunodeficiency virus (HIV)-infected participants in Baltimore, Maryland were enrolled in a study that investigated HIV/antiretroviral therapy-associated comorbidities. Multiple linear and logistic regression models were fitted to examine the associations between PI therapy and lipid profiles for the pooled sample and cocaine use subgroups, respectively. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, and atherogenic index of plasma (AIP) levels were positively associated with duration of PI-based therapy in long-term cocaine users (all p < 0.05). However, longer-term PI therapy was significantly associated with increased HDL-C in non-chronic cocaine users (β = 0.109, SE = 0.042, p < 0.05). The participants who received PI therapy ≥12 months and used cocaine ≥15 years were more likely to have hypertriglyceridemia (OR = 2.82, 95% CI = 1.63, 4.88) and abnormal AIP (OR = 1.73, 95% CI = 1.08, 2.79) as compared to their counterparts. Our findings showed that long-term cocaine use may exacerbate adverse effects of PI therapy on lipid metabolism, suggesting that reduced cocaine use may be considered an alternative approach to managing PI-associated dyslipidemia in chronic cocaine users with HIV infection.
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