New Guidelines for the Use of Cholesterol-Lowering Drugs with HAART
September 7, 2000
Elevated triglycerides and cholesterol are an increasingly common concern for HIV-positive people, especially those on highly active antiretroviral therapy (HAART). Abnormally high levels of triglycerides and cholesterol, known as dyslipidemia, have proven to increase a person's risk for serious diseases such as coronary heart disease (CHD), diabetes and pancreatitis.
Dietary and behavioral changes such as eating a low-fat diet and getting more exercise are always recommended for people with elevated cholesterol or triglycerides levels. A group of medications known as statins are also often used to lower cholesterol levels when non-pharmaceutical changes don't have the desired effect. The correct way to use statins for HIV-positive people, however, is not yet clear because of the interactions between statins and protease inhibitors sometimes used in HAART.
In order to help individuals and their healthcare providers figure out how to address dyslipidemia in HIV-positive individuals, a group of community members and researchers affiliated with the Adult AIDS Clinical Trials Group (AACTG) came up with a set of guidelines. The group, known as the Cardiovascular Disease Focus Group of the AACTG, posted preliminary guidelines for the evaluation and management of dyslipidemia in HIV-positive adults in May of this year.
Background and Guidelines
Dyslipidemia is the term for abnormal levels of blood lipids. Lipids are fats, and the term is usually used to refer to both cholesterol and triglycerides. When lipid levels are measured, values are obtained for total cholesterol, HDL, and triglycerides. These numbers are then used to calculate values for LDL and VLDL.
Guidelines for when to initiate treatment for elevated cholesterol are published by a division of the National Institutes of Health known as the National Cholesterol Education Program (NCEP). According to the Cardiovascular Disease Focus Group, these suggestions are appropriate for HIV-positive people. The NCEP recommends dietary changes or drug therapy based on an individual's LDL cholesterol levels and the number of other risk factors he or she has for CHD.
For people with fewer than two risk factors, dietary intervention is recommended if LDL levels exceed 160mg/dL and drug therapy should be considered if levels are above 190mg/dL. For people with two or more risk factors, the intervention levels are 130mg/dL and 160mg/dL.
Non-pharmaceutical behavioral and dietary changes are recommended for anyone with a fasting triglyceride level over 200mg/dL. If these levels don't respond to changes in diet and exercise, however, it is still unclear at what level to begin therapy for hypertriglyceridemia. It is clear that people with extremely high levels, above 2000mg/dL, should start both drug and non-drug therapies. Because levels above 1000mg/dL indicate an increased risk of pancreatitis, therapy should be seriously considered at this level as well. People with a history of pancreatitis may want to consider medication starting at 500mg/dL. The complete text version of the NCEP guidelines are on the web at: http://www.nhlbi.nih.gov/guidelines/cholesterol/atp.txt.
If dietary and behavioral changes fail to bring about the desired decrease in a person's lipid levels, medication may be considered. For high cholesterol, a group of drugs known as statins are usually prescribed. The Cardiovascular Disease Focus Group's report points out two potential complications of taking both protease inhibitors (PIs) and statins. One is that PIs may interfere with the breakdown of statin drugs, causing the statins to remain in the body longer than they should. This means that the amount of statin is higher than intended and may cause more side effects. The other possibility is that statins may lower the levels of PIs by prematurely inducing their breakdown, decreasing the ability of HAART to control the replication of HIV.
The following is a list of statin drugs (also known as HMG-CoA reductase inhibitors) used to treat high cholesterol. The possible interactions with HAART are also listed.
Another group of drugs, called fibrates, includes the drugs gemfibrozil (Gemcor, Lopid) and fenofibrate (Tricor). Fibrates are also used to treat high cholesterol when a person also has high triglycerides. Although it is unlikely that fibrates and PIs interact directly, the Cardiovascular Disease Focus Group recommends caution when using both groups of drugs because the risk of side effects increases when fibrates and statins are used together.
The Cardiovascular Disease Focus Group summarized their recommendations for HIV care providers by saying: "Given the potential for interactions, it is reasonable to recommend the use of low initial dosages of either pravastatin (20mg daily) or atorvastatin (10mg daily) in HIV patients who require drug therapy for hypercholesterolemia and who are taking PIs. Fluvastatin and cerivastatin are acceptable alternative agents, but no data on interaction with PIs have been reported. Lovastatin and simvastatin should be avoided." The complete text of the AACTG guidelines can be found on-line at http://aactg.s-3.com/pub/docs/lipid_guidelines.htm.
This article was provided by Seattle Treatment Education Project. It is a part of the publication STEP Ezine.