Drugs suspected to be involved in the DDI
Complete list of drugs taken by the patient
Atorvastatin 40 mg qd
Clinical case description
59-year-old male with long-term HIV infection. Always on cART containing boosted protease inhibitors. No virologic failures. Currently on Darunavir/cobicistat/FTC/TAF. Last viral load determination <20 copies/mL; CD4+ T cell count 53 cells/mm3. Heavy smoker, hypercholesterolemia. 10-year risk of MI or death 15% (Framingham Risk Score). On treatment with atorvastatin 40 mg qd. NO evidence of statin-associated toxicity (liver enzyme levels and CK within normal range). Lipid levels above the target (LDL 115 mg/dL; target <70 mg/dL). Darunavir/cobicistat/FTC/TAF was changed to Bictegravir/FTC/TAF. Three months after the change viral load continued <20 copies/mL, LDL-c levels decreased to 55 mg/dL. This is an example on how ritonavir and cobicistat may interfere with statins mechanism of action, limiting their efficacy.
Drug Interaction Probability Scale (DIPS)
Personal information from the specialist
Atorvastatin is a substrate of the hepatic transporter OATP1B1 which factiliates its entry in the liver, the site of action and elimination. Darunavir/cobicistat inhibits OATP1B1 and therefore can limit the entry of atorvastatin in the liver which may impait its lipid lowering effect. An analysis of the Swiss HIV Cohort Study (Courlet P et al. J Antimicrob Chemother 2020) reported indeed that insufficient lipid control was observed with boosted protease inhibitors despite high atorvastatin concentrations likely explained by the inhibition of OATP1B1 but also their less favorable effect on lipid. Target lipid values were more often achieved with unboosted integrase inhibitors due to both their favourable DDI profiles and neutral effect on lipids. The authors conclude that integrase inhibitor-based regimens should be favoured in patients with refractory dyslipidaemia.