HIV lipodystrophy appears to actually be composed of two distinct, but overlapping syndromes. The first and most commonly observed is the loss of fat from the subcutaneous regions, termed lipoatrophy. The second types of body shape changes are fat accumulation -- known as lipoaccumulation or central adiposity.
The lack of a universally agreed-upon definition of the lipodystrophy syndromes has made their characterization difficult. Typical features of lipoatrophy include the thinning of the fat in the face, arms, legs, trunk and buttocks. Particularly troublesome, because of the potential for being visually stigmatizing, lipoatrophy has influenced the choice of antiretroviral therapy for many individuals. Lipoaccumulation is characterized by unusual accumulation of fat -- typically in the neck, breasts or in the internal abdominal region. A recent controversial study, called FRAM has challenged the notion that fat accumulation is more common among persons with HIV infection.
A great deal of attention has been directed at the possible association between HIV medications and lipodystrophy. Several recent studies have identified a strong link between the use of the nucleoside reverse transcriptase inhibitor (NRTI) stavudine (Zerit, d4T) and fat atrophy. Indeed, the replacement of stavudine with other NRTIs is associated with a slow gain in peripheral fat, consistent with a role of the drug in causing fat loss. This medication switch approach has had only limited symptomatic benefit to patients, so patients and clinicians continue to search for effective treatments. Some centers have used a synthetic polymer, called New-Fill as a temporary cosmetic relief of the fat thinning of the face.
Several studies have shown a risk of fat accumulation with the use of PIs, though this has not been universally agreed upon. The replacement of PIs with other classes of medications has not been associated with improvements in body shape. A small study used high-dose niacin as treatment of abdominal lipoaccumulation with success in a majority of patients. Confirmation of these data would have the potential to benefit patients with this type of body change.
Several classes of antiretroviral medications are associated with causing hyperlipidemia, particularly the protease inhibitors. Ritonavir-boosted PIs seem to be at greatest risk for causing hyperlipidemia. Newer PIs, particularly the investigational drug Atazanavir, may cause little or no hyperlipidemia. The use of the non-nucleoside reverse transcriptase inhibitors, efavirenz (Sustiva, Stocrin) and nevirapine (Viramune) have been shown to cause alterations in cholesterol levels, with slight increases in total cholesterol. This elevation was largely caused by increases in the good- or HDL-cholesterol. Because of this, persons on these drugs have modest improvements in their cardiac-risk indices (or total cholesterol/HDL ratio). A recent presentation of the "2NN" trial at this year's Conference on Retroviruses and Opportunistic Infections compared efavirenz-based therapy to nevirapine-based therapy in treatment naive persons. Analysis of the lipid effects in this study showed statistically significant differences between the two NNRTIs, with improved cardiac risk ratio and HDL cholesterol among persons who received nevirapine.
Recently, multiple studies have confirmed that the NRTI, stavudine also causes increases in LDL-cholesterol and triglycerides. These later observations came at considerable surprise, because it was long believed that the NRTIs did not alter lipid levels. Other NRTIs, zidovudine (Retrovir), abacavir (Ziagen) and tenofovir (Viread) have been shown to cause significantly less hyperlipidemia.
The approach to the treatment of hyperlipidemia in the HIV-infected person requires a comprehensive view of treatment options, both for HIV and for the hyperlipidemia. Recommendations for the treatment of hyperlipidemia are published, and depend on the number of additional cardiovascular disease risk factors (like high blood pressure, diabetes, obesity, smoking or family history) that the person has and whether the hyperlipidemia is affected greater by elevations in cholesterol or by elevations in triglycerides. Reduction of modifiable risk factors, like quitting smoking or controlling hypertension, is always advisable. If appropriate, avoidance of antiretroviral medications that cause significant hyperlipidemia would be the simplest approach. Where changing antiretroviral medications cannot be achieved, lipid-lowering agents can be prescribed. These drugs represent two major classes, known as "statins" and "fibrates." Their administration must be done carefully and with monitoring, since there is a potential for undesirable drug-drug interactions, particularly when taken with PIs.
Benjamin Young, M.D., Ph.D.
Denver ID Consultants
4545 East Ninth Avenue, Suite 120
Denver, CO 80220
(303) 320-1953 (fax)
Benjamin Young, M.D., Ph.D. is from the Rose Medical Center, Denver, Colorado.
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