What is the most appropriate once-daily statin for a 45-year-old male with HIV (Human Immunodeficiency Virus) infection, taking darunavir (Prezista) (darunavir) plus cobicistat (Tybost) (cobicistat) plus emtricitabine (Emtriva) (emtricitabine) plus tenofovir alafenamide (Vemlidy) (tenofovir alafenamide), with hyperlipidemia and a 9% estimated 10-year risk of atherosclerotic cardiovascular disease (ASCVD)?

Statin Selection for HIV Patient on Darunavir/Cobicistat

Rosuvastatin 10 mg once daily is the most appropriate statin for this patient, as it provides moderate-intensity therapy with acceptable drug-drug interaction profile when combined with darunavir/cobicistat. 1

Rationale for Rosuvastatin Selection

Risk Assessment and Treatment Indication

• This patient has HIV with a 9% 10-year ASCVD risk, which falls into the 7.5-10% range where moderate-intensity statin therapy is recommended 2
• HIV itself is considered a risk-enhancing factor that favors moderate-intensity statin therapy in patients with 7.5% or higher 10-year ASCVD risk 2
• The patient does not meet criteria for high-intensity statin therapy (which requires ≥20% 10-year risk or established ASCVD) 3

Critical Drug-Drug Interaction Considerations

Simvastatin is absolutely contraindicated with darunavir/cobicistat due to severe CYP3A4 interactions that dramatically increase myopathy and rhabdomyolysis risk 1

Atorvastatin requires extreme caution with protease inhibitors:

• Must start at the lowest dose (10 mg) when combined with boosted protease inhibitors 1
• The recommended dose for moderate-intensity therapy is 20 mg, but this requires careful monitoring with darunavir/cobicistat 1
• While acceptable, it is not the optimal first choice given interaction concerns 1

Pravastatin has a specific problematic interaction with darunavir:

• Darunavir increases pravastatin AUC by 81% 1
• This makes pravastatin less favorable despite its generally good profile with other protease inhibitors 1, 2

Rosuvastatin 10 mg is acceptable with appropriate monitoring:

• Provides moderate-intensity LDL-lowering (30-50% reduction) 1
• International Antiviral Society-USA Panel guidelines specifically recommend rosuvastatin 10 mg as an acceptable moderate-intensity option for people with HIV 1
• Requires monitoring for muscle symptoms and baseline/periodic liver function tests 1

Alternative Consideration: Pitavastatin

• Pitavastatin has minimal drug-drug interactions with protease inhibitors, showing only a 31% increase in AUC with darunavir/ritonavir 4
• However, pitavastatin is not available as a generic and may have cost/access limitations 4
• If available, pitavastatin 2-4 mg would be an excellent alternative 1

Monitoring Requirements

Baseline assessment:

• Liver function tests (ALT, AST) 1
• Creatine kinase if symptomatic 2

Patient counseling on statin toxicity signs:

• Muscle pain, weakness, or tenderness 1
• Dark urine 1
• Unexplained fatigue 2

Ongoing monitoring:

• Periodic liver function tests 1
• Lipid panel at 4-12 weeks to assess response 2
• Continue monitoring HIV viral suppression 3

Common Pitfalls to Avoid

• Never use simvastatin or lovastatin with any cobicistat-containing regimen 1
• Do not start atorvastatin at doses >20 mg when combined with protease inhibitors due to increased drug exposure 1
• Remember the specific darunavir-pravastatin interaction (81% AUC increase) that makes pravastatin less favorable in this specific combination 1
• Avoid assuming all statins are equivalent in HIV patients on antiretroviral therapy—drug-drug interactions must guide selection 2