Postprandial lipid effects of low-dose ritonavir vs. raltegravir in HIV-uninfected adults

Abstract

In HIV-uninfected adults, postprandial LDL cholesterol excursions with low-dose ritonavir were significantly greater than those with raltegravir. This postprandial effect of ritonavir increased by about 50% the previously observed adverse effect of ritonavir on fasting LDL cholesterol, and so may explain some of the hitherto unexplained association of protease inhibitor-based therapy with cardiovascular disease.

Pharmacokinetics of darunavir in fixed‐dose combination with cobicistat compared with coadministration of darunavir and ritonavir as single agents in healthy volunteers

“…Firstly, adverse events (AEs) are not uncommon with ritonavir, with disturbance of taste and gastrointestinal disorders being the most frequently reported . In addition, low‐dose ritonavir has been associated with hyperlipidemia . Secondly, ritonavir is also an inhibitor of CYP2D6, breast cancer resistance protein (BCRP) and P‐glycoprotein, and induces the expression of several CYP enzyme isoforms including CYP1A2, CYP2B6, CYP2C9, CYP2C19, and glucuronosyl transferase.…”

Raltegravir in HIV-1 Infection: Safety and Efficacy in Treatment-Naïve Patients

“…In HIV-1 uninfected individuals, raltegravir (400 mg twice a day) induced much less postprandial (after meal) lipid changes compared to the low dose of ritonavir (100 mg once a day). 84 In summary, generally the patients switching to raltegravir based treatment from most other regimens observed similar potent antiviral efficacy with an added advantage of less severe adverse events.…”

Twenty years of boosting antiretroviral agents

“…The low doses used today in clinical practice are much safer and remarkably better tolerated. However, ritonavir doses of 100 mg once or twice daily have been shown, both in healthy volunteers and in HIV-infected patients, to be associated with significant increases in total cholesterol, low-density lipoprotein cholesterol and triglycerides, and decreases in high-density lipoprotein cholesterol in a concentration-dependent manner [11][12][13]. Importantly, when using PI/r, it is often difficult to isolate the ritonavir-related adverse effects from the active protease inhibitor.…”