By Liz Highleyman

Since the advent of HAART in the mid-1990s, people with HIV and their healthcare providers have grown increasingly concerned about long-term metabolic complications associated with antiretroviral drugs. These complications include body fat alterations, blood glucose and insulin abnormalities, and changes in blood lipids that may increase the risk of cardiovascular disease.

Thus, dealing with metabolic manifestations has become a larger aspect of HIV care. Revised European AIDS Clinical Society (EACS) recommendations for prevention and management of metabolic complications in HIV positive people treated were presented October 26, 2007 at the 11th annual EACS conference in Madrid, Spain.

The panel members note that in HIV-infected people, both uncontrolled viral replication and antiretroviral therapy can contribute to metabolic diseases. They add that management of these conditions may involve use of additional medications, thereby increasing the risk of side effects, drug interactions, altered blood levels, and poor adherence.

They also note that there is a limited evidence from randomized controlled trials about management of metabolic complications in people with HIV, so much of current practice is based on the standard of care for the general HIV negative population. The panel did not cover kidney side effects, bone loss, or sexual dysfunction, all of which may have a metabolic component.

Screening for Metabolic Diseases

Screening for metabolic disease in people with HIV should include assessment of risk factors for cardiovascular disease including:

These assessments should be done at the time of HIV diagnosis, before starting antiretroviral therapy, and annually thereafter. Cardiovascular disease risk assessment and electrocardiograms (ECG) should be done before starting therapy and yearly thereafter.

Prevention of Cardiovascular Disease

Estimates of cardiovascular risk are based on standard formulas derived from information about the general population. Steps to take to prevent cardiovascular disease depend on risk level according to the Framingham equation:

The guidelines include further information about smoking cessation (nicotine replacement therapy and anti-smoking medications such as bupropion [Zyban] are recommended if needed), optimal diet (limit total and saturated fat, eat vegetables, fruits, low fat meat and dairy products), and exercise (an overall active lifestyle is best, cardiovascular fitness activities for 30 minutes 5-7 days per week is recommended).

Management of Abnormal Blood Lipid Levels

The guidelines discuss use of lipid-lowering medications if lifestyle changes are not sufficient to reduce cardiovascular risk.

The statin drugs are used to lower cholesterol. Simvastatin (Zocor) is contraindicated and atorvastatin (Lipitor) is not recommended due to drug interactions with protease inhibitors. Fluvastatin (Lescol), pravastatin (Pravachol), and rosuvastatin (Crestor) may require dose adjustment when used with HAART.

The guidelines also offer advice about other drugs used to manage cholesterol and/or triglycerides -- including ezetimibe (Zetia), acipimox, fibrates, and omega 3 fatty acid supplements (for example, fish oil) -- and information about which to use and when based on patients' current cholesterol and triglyceride levels.

With regard to selecting a HAART regimen, the panel ranks antiretroviral drugs in terms of their metabolic impact as follows:

Management of Body Fat Changes

Recommendations for lipoatrophy (fat loss, especially in the face and limbs) include:

Recommendations for lipohypertrophy (fat gain, especially in the trunk or abdomen) include:

The panel notes that there is "no proven strategy" for preventing lipohypertrophy, and that the management options have not been proven to provide long-term benefit and may cause new complications.

Treatment of Blood Glucose Abnormalities

The guidelines discuss cut-offs for diagnosing impaired fasting glucose, impaired glucose tolerance, and frank type 2 diabetes based on fasting plasma glucose and oral glucose tolerance tests.

Interventions for managing blood glucose abnormalities are:

The panel notes that there are insufficient data about use of other types of anti-diabetic drugs (such as sulfonylureas or glucosidase inhibitors) in HIV positive people on HAART.

Prevention and Management of Hyperlactatemia

Elevated lactate (lactic acid) in the blood, or hyperlactatemia, is a potential side effect of certain NRTIs associated with mitochondrial toxicity. Lactic acidosis is a severe, life-threatening buildup of lactic acid in the body.

Known or suspected risk factors for hyperlactatemia include:

As a prevention strategy, the panel recommends avoiding d4T + ddI (or switching if a person is already taking this combination).

Routine monitoring of lactate acid levels is not recommended, even for high-risk patients, since this does not predict who will develop lactic acidosis. Lactic acid and related biochemical markers should be measured if a person has symptoms of hyperlactatemia (nausea, abdominal pain, enlarged liver, unexplained weight loss).

If a patient's lactate level is below 5 mmol/L with no symptoms, no action need be taken besides continued monitoring. If it is 2-5 mmol/L with symptoms, or > 5 with or without symptoms, consider removing all NRTIs from the regimen or substituting a NRTI less likely to cause these problems (3TC, emtricitabine, abacavir, tenofovir).

Management of Hypertension

The panel provides a detailed matrix of diagnostic criteria and recommended interventions for hypertension (high blood pressure). These include lifestyle changes (smoking cessation, diet, exercise) and anti-hypertensive medications.
Finally, they provide indications and contraindications for a wide range of blood pressure-lowering drugs including diuretics, beta blockers, calcium channel blockers, and ACE inhibitors.

10/30/07

Source
European AIDS Clinical Society. Guidelines for the Clinical Management and Treatment of Chronic Hepatitis B and C co-infection in HIV-infected Adults. Presented at the 11th European AIDS Conference. Madrid, Spain. October 26, 2007.