A common complaint among HIV-positive people taking antiretroviral drugs-especially women-is an increase in abdominal size. While this is likely due to fat buildup around the gut, it's important to figure out what kind of fat buildup it is. Fat, especially fat around the gut, can be broken down into two different categories: visceral fat and subcutaneous fat. Visceral fat increases occur deep down inside the body, often in and around the muscle tissue and the organs inside the body. This can leave the stomach feeling hard, even though there is a buildup of fat underneath. Subcutaneous fat increases are those that occur under the skin. This type of fat feels softer and more "fleshy."
An increase in visceral fat is associated with increased risk for heart disease, while an increase in subcutaneous fat, though not necessarily desirable, is not as dangerous in terms of overall health.
Even though visceral fat increases are a more worrisome symptom of lipodystrophy, Dr. Kotler noted that both HIV-positive and HIV-negative people experience this. In fact, as women age, some develop visceral fat deposits in the upper body due to hormonal changes.
Distinguishing between visceral and subcutaneous fat will be important for researchers to look at in future studies. It will be important to see how changes in visceral and subcutaneous fat among people living with HIV, including those receiving antiretroviral therapy, differ from HIV-negative people. This will help figure out how different lipodystrophy is from "natural," age-related changes in body fat.
Some Changes in Body Fat May be Reversible
Some experts have suggested that, once fat begins disappearing in the legs, arms, or face, it may never come back again. Fortunately, some new data have proved them wrong.
In a study performed by Dr. Thierry Saint-Marc and colleagues, 36 HIV-positive study volunteers stopped their d4T (Zerit) in an effort to reverse the fat loss they had been experiencing. After 9 months of stopping d4T, an average fat increase of 32% was seen in the patients' thighs. Eleven subjects reported a major improvement in fat loss and 21 reported partial improvement.
In another study, conducted by Dr. Andrew Carr and his colleagues in Sydney, Australia, study volunteers switched their protease inhibitor-based regimen to a non-nucleoside analogue-based regimen; earlier studies suggested this might work, so Dr. Carr's team hoped for the best. Switching led to reduced fat in the abdomen (although no distinction was made between visceral fat and subcutaneous fat), and decreases in some blood lipid levels. Unfortunately, even among patients who switched therapies, fat loss in the limbs was still seen, as was a decrease in muscle mass.
The Tape Measure Alwasy Lies
Over the years, dating back to early wasting syndrome studies, researchers have relied on a simple measurement to look for body shape increases or decreases around the gut: the waist-to-hip ratio. Let's consider an example. If you have a 28-inch waist and 36-inch hips, your waist-to-hip ratio (WTH) is .78. If you experience an increase in waist size to 32 inches, along with an increase in hip size to 41 inches, your WTH would remain constant at .78. If you experience an increase in waist size to 32 inches, but your hip measurement remains constant at 36 inches, your WTH increases to .89. WTH is an ideal way to track changes in abdominal size because it does not increase if there is an overall increase in measurements-it only captures increases in waist size relative to the rest of the body.
WTH measurements can be misleading, however. Dr. Kotler pointed out that in some of his patients, WTH is definitely increased. But some patients weren't really experiencing an increase in the waist size, but instead a decrease in their hip size. This is very similar to what he saw when a lot of patients had wasting syndrome prior to the availability of HAART. There's clearly more to these measurements than meets they eye.
It's Different for Some
Drawing upon Dr. Kotler's discussion of different symptoms in different people, Dr. Raghavan presented data suggesting that lipodystrophy does not affect all groups of people in the same way. For example, fat accumulation (usually in the breasts and/or abdomen) is more common in women, while fat depletion (loss of fat in the arms, legs, and face) is more often observed in men. According to Dr. Raghavan, some studies have shown that there is a lower prevalence of fat redistribution in African-Americans, compared to whites. Moreover, African-Americans and Latinos/as are less likely to develop high blood lipid levels (including triglycerides and cholesterol) than their white counterparts.
Older age is a risk associated with complications like heart disease and stroke in HIV-positive men and women, but this is also true for HIV-negative people. Family history must also be considered; a review of data involving almost 1400 HIV-positive subjects showed that 100% of those with high blood sugar had a family history of diabetes.
You Are What You Eat (and Treat)
Given that research into the possible cause-or causes-of lipodystrophy is still so new, it's not surprising that we don't know how to treat it correctly. But Drs. Kotler and Raghavan both concluded that diet and exercise can play an important role in controlling symptoms. A well-balanced diet with a reasonable fat intake-less than 30% of total calories from fat-has a positive impact on overall health and can reduce blood fat and sugar levels. And not only can exercise help strengthen the heart, but it can also help reduce fat accumulation around the waist and build muscle mass in the arms and legs.
As discussed above, high blood lipid levels greatly increase the risk of experiencing heart disease, a heart attack, or a stroke. To help control these levels, several lipid-lowering drugs - called "statins" - are available and are being studied in HIV-positive people with lipodystrophy. In a recent study three statins-pravastatin (Pravachol), simvastatin (Zocor), and atorvastatin (Lipitor)-were given to HIV-positive individuals taking a combination of ritonavir (Norvir) and saquinavir (Fortovase) to see if any drug interactions occurred. The results have important implications. Zocor increased the blood level of the protease inhibitors by 31%, and therefore should not be taken with these drugs. Protease inhibitor blood levels was decreased slightly by Pravachol and increased slightly by Lipitor. As a general recommendation, Lipitor should be used at a dose of 40 mg/day, which is half the standard dose, when used with these-and other-protease inhibitors. Always discuss your specific situation with your primary care provider.
Questions and Answers
Q: You mentioned L-carnitine. How should I use it?
A: L-carnitine may help prevent lactic acidosis, a condition in which the liver is unable to convert lactic acid to glucose, resulting in high levels of lactic acid in the blood. This condition, which can be fatal, is more common in women than in men and is associated with NRTI use. There is no proof that L-carnitine prevents lactic acidosis, but it certainly can't hurt.
Q: Can diabetes go away on its own?
A: An individual may exhibit insulin resistance, meaning that body cells are not efficiently using insulin to remove glucose from the bloodstream. This condition can result in high glucose levels, which will appear as a lab abnormality. Insulin resistance may reverse without ever becoming symptomatic diabetes.
Q: I am trying to avoid fat depletion. Should I start with a regimen that combines PIs and NNRTIs and does not include NRTIs?
A: No. If you use PIs and NNRTIs together in an initial treatment regimen, you may become resistant to both classes of drugs, making it difficult to construct a salvage regimen if your initial regimen becomes ineffective.
There is some indication that the thymidine NRTIs (AZT and d4T) are more likely to cause fat depletion than the non-thymidine NRTIs (ddI, 3TC, and FTC, an experimental NRTI).
Forum summary writer - Anne Monroe
