Lipid-lowering drugs

In HIV-negative people with high lipids, several types of drugs are used to lower lipid levels. These drugs are used to treat high lipids or coronary heart disease in people who have not responded to dietary changes, and include:

• CoA reductase inhibitors, or statins, which reduce cholesterol production in the liver but may interact with protease inhibitors.
• Fibrates, which reduce levels of triglycerides and LDL cholesterol.
• Anion-exchange resins, which lower LDL cholesterol but can aggravate high triglycerides and thus should not be used to treat HIV-related high lipids.
• Nicotinic acid or niacin, which reduces the production of triglycerides and cholesterol.
• Fish oils, which contain fatty acids of the omega-3 group which may reduce LDL cholesterol and increase HDL cholesterol at high doses.

If a person has extremely high lipids, or if initial therapy with a single class has been unsuccessful, drugs from more than one class of lipid-lowering drugs can be combined. However, combining statins with either nicotinic acid or a fibrate increases the risk of side-effects, including a potentially life-threatening condition called rhabdomyolysis, where muscle cell products are released into the blood causing severe muscle pain, swelling and possibly damage to the vital organs.

American HIV Dyslipidemia Guidelines have been drafted to guide clinicians in the monitoring and treatment of people taking antiretroviral therapy with elevated lipids. These guidelines recommend that HIV-positive patients should be treated in line with the National Cholesterol Education Program, although clinicians should select treatments which are least likely to lead to drug interactions. ¹ A number of trials have found that lipid-lowering agents can reduce cholesterol and triglyceride levels among people on protease inhibitors. In many instances, lipid-lowering agents produce only moderate benefit.

A study from Houston, Texas, showed that in patients with high lipid levels, lipid-lowering therapy was only partially successful. Sixty-three consecutive patients were analysed. An average cholesterol reduction of 19% was reported on the first lipid-lowering regimen (predominantly fibrates), and LDL cholesterol levels fell by just 5%. Only 16% of patients who continued protease inhibitor therapy achieved target levels of LDL and total cholesterol after more than one year of lipid-lowering treatment. Presenting the study, Dr Fahmida Visnegarwala said that management of dyslipidemia alone without correcting the underlying metabolic disturbances may not be effective, but a disappointingly small proportion of non-HIV patients (typically less than 40%) ever reach the lipid goals set out at the beginning of lipid-lowering therapy.

However, a randomised Italian study found that lipid-lowering treatment with either a statin or fibrate was more effective than switching from a protease inhibitor to efavirenz or nevirapine in controlling lipid levels. ² The study randomised 132 patients with elevated lipid levels to switch from their protease inhibitor-containing regimen to nevirapine or efavirenz, or to stay on their PI-containing regimen and add either pravastatin (Lipostat) or bezafibrate (Bezalip).

Patients treated with lipid-lowering drugs experienced a 44% decrease in triglycerides, compared to a mean decrease of 18% in the NNRTI-treated group. Total cholesterol levels fell more substantially in the patients treated with lipid-lowering drugs than in the NNRTI group too (41 vs 19%), and a similar pattern held true for low-density lipoprotein (LDL) cholesterol.

With these cautions, people with the following risk factors are more likely to be encouraged to take lipid-lowering drugs and pursue the interventions discussed in previous sub-sections on the basis of current knowledge:

• High blood pressure (hypertension).
• A prior history of cardiovascular disease.
• A family history of heart disease.
• Silent myocardial ischemia.