- PIs can cause hypertriglyceridaemia and elevated low-density lipoprotein cholesterol (LDL-C).
- ATV/r and DRV/r are associated with less significant lipid abnormalities than LPV/r.
- EFV can cause elevated total cholesterol (TC) and mild hypertriglyceridaemia.
- DTG does not significantly affect cholesterol.
- Lipids should be assessed routinely after 3 months on a PI regimen.
PIs can cause hypertriglyceridaemia and elevated LDL-C. ATV/r and once-daily DRV/r (800 mg/100 mg DRV/r once daily) are associated with less severe dyslipidaemia than other boosted PIs; AZT can cause mild hypertriglyceridaemia, and EFV can cause elevated total cholesterol (TC) and mild hypertriglyceridaemia.
We suggest that lipids should be assessed routinely after 3 months on a PI regimen. If normal at this stage, then reassessment should be performed only in those with cardiovascular risk factors. Diet and lifestyle modification should always be advised. Diet is more effective for controlling hypertriglyceridaemia than hypercholesterolaemia. Other cardiovascular risk factors should be addressed. Clinicians should consider and investigate secondary causes of hypertriglyceridaemia and hypercholesterolaemia (e.g. diabetes, nephrotic syndrome, alcohol abuse and hypothyroidism).
If patients receiving LPV/r develop significant dyslipidaemia, then they should be switched to DRV/r or ATV/r, rather than adding lipid-lowering therapy. However, lipid-lowering therapy is indicated in patients with persistent elevations despite switching to DRV/r or ATV/r. Switching the PI to DTG is another option, because DTG has a more favourable lipid profile than PIs. However, DTG should only be used in a regimen in which at least one other ART drug is known to be fully active. In patients with hyperlipidaemia on EFV, the drug should be switched to DTG or RPV.
Marked hypertriglyceridaemia (> 10 mmol/L) can cause pancreatitis and requires urgent treatment with diet modification (restrict total TG intake to < 30 g/day), fibrates and switching of LPV/r to DRV/r, ATV/r or DTG. (Fibrates can be stopped after 1 month, followed by reassessment within 4–6 weeks.)
Indications for statin therapy in HIV-positive patients should be the same as in HIV-negative patients, using the Framingham heart disease risk score. As a general rule, in young patients with isolated elevated cholesterol but no other cardiovascular risk factors, a threshold of TC > 7.5 mmol/L (or LDL-C > 5.0 mmol/L) should be used for initiating statin therapy; and the patient should be referred to a lipid clinic for investigation if feasible. In patients with cardiovascular risk factors (e.g. smoking, diabetes, hypertension), decisions should be made using the Framingham heart disease risk score. All patients with established atherosclerotic disease (coronary, cerebral or peripheral) or familial hypercholesterolaemia should be started on statin treatment. In addition, type 2 diabetics should also be started on a statin if they have chronic kidney disease, or if they are aged > 40 years (or have had diabetes for > 10 years) and have one or more additional cardiovascular risk factors.91
Many statins have interactions with PIs that can lead to potentially toxic statin concentrations, with the exception of pravastatin and fluvastatin. Atorvastatin concentrations are significantly raised by PIs, but low doses (maximum 10 mg daily) can be used with monitoring for symptoms of myalgia. Lovastatin and simvastatin should not be co-administered with PIs, as their concentrations are dramatically increased, and severe rhabdomyolysis has been reported. We also advise against the use of rosuvastatin with PIs due to a complex drug-drug interaction: PIs increase the plasma concentrations of rosuvastatin while reducing their efficacy in the liver.
|Common pitfall: Not routinely assessing lipids while the patient is receiving PI-based ART.|
|Common pitfall: Failure to recognise that many statins have interactions with PIs that lead to toxic statin concentrations.|
|Common pitfall: Monitoring of LDL-C in patients on a high-dose statin for secondary prevention. Such monitoring is not necessary.|