Short Term Side Effects
As one expects, people may experience many short-term effects due to ARV therapy. Dr. Raghavan discussed several of them. Nausea and vomiting is one of the most frequently reported short-term side effects, which is often resolved within two to three weeks into therapy. Diarrhea was a close second, especially frequent in individuals taking Viracept (nelfinavir), Videx (ddI), or Norvir (ritonavir). Kidney stones, a relatively common side effect of Crixivan (indinavir), appear to be slightly more frequent in women. Stones occur largely due to dehydration, and the most effective prevention is to drink 1.5 liters of water (at least 8 glasses!) a day.

Dr. Raghavan presented a number of suggestions for treating Viracept associated diarrhea. Metamucil, and other fiber supplements containing psyllium husk, can be effective in combating diarrhea in some patients. Calcium supplements are also helpful. Dr. Raghavan prescribes 500mg, twice a day, for patients suffering from Viracept associated diarrhea. Additional benefits of calcium supplements include prevention of osteopenia or osteoporosis, which are commonly being reported in HIV patients. Acidophilus/bifidobacteria (two types of bacteria found in yogurt) in combination with soluble fiber can also help fight diarrhea associated with ARV medications. Supplements containing glutamine are also effective, although to a lesser extent.

Long Term Effects
Dr. Raghavan described several body appearance changes that have been reported in conjunction with ARV use. These changes are often referred to as lipodystrophy and can include both fat accumulation related changes and/or fat loss related changes.

According to Dr. Raghavan, fat accumulation related changes are much more common among African American patients at Harlem Hospital Center than fat loss related changes. Close to 50 % of patients on ARV therapy at Harlem Hospital Center experience obesity and/or fat gain related body appearance changes. Wasting, with the exception of chronic drug users, is not as common. Fat accumulation comes in many forms, one form being the buffalo hump, a mound of fat on the upper back just below the nape of one's neck. Visceral obesity, an increase in girth in the abdominal area, is another long-term problem associated with ARV therapy. An increase in breast size in both men and women (gynecomastia) is also common.

Dr. Raghavan introduced the subject of lipodystrophy by asking the audience for their definitions. It quickly became apparent that we have no clear definition of this syndrome. Confusion about what lipodystrophy is has made it difficult to find ways to treat or reverse the syndrome. Dr. Raghavan stressed that lipodystrophy is fat redistribution, which can be fat loss, gain, or both. Many individuals suffering from lipodystrophy experience facial wasting, loss of fat in the arms, legs and butt. However, some of these same people will also experience an increase in breast and stomach fat. Among patients suffering from lipodystrophy, subcutaneous fat (fat under the skin) is lost from the legs, arms, and face, and there is a gain in fat at the midsection, where fat relocates deep below the skin. This is known as visceral fat. Visceral fat in the abdomen in HIV negative populations is often associated with increased risk of heart disease. Currently, there are no agents available that can reverse loss of subcutaneous fat in arms, legs, face and buttocks. However, exercise therapy has shown to reduce visceral fat in the abdominal region in some people.

Prevalence & Predictors of Metabolic Complications in HIV+ Individuals in Post-HAART Era
Just how common are these conditions? According to Dr. Raghavan, less than 5% of her HIV+ patients have buffalo hump. Abdominal obesity is found in about 40-50% of her patients, and loss of fat in arms, legs, face and buttocks in 25-27% of the patients.

Data for lipodystrophy vary quite a bit, depending on how people define the term, the data collection methods and the type of subjects studied. Lack of consensus on the exact definition makes it hard to compare the data across studies, leading to a lot of confusion on the magnitude of the problem.

One thing is clear: antiretroviral therapy also seems to directly, or indirectly, contribute to a number of other metabolic complications, such as increases in glucose, insulin resistance, triglyceride and cholesterol levels, lactic acidosis, hypertension and cardiovascular complications. Dr. Raghavan provided several examples. However, different protease inhibitors (PIs) seem to exert different metabolic side effects. Norvir (ritonavir), a PI, has been shown to significantly increase lipid levels, whereas Crixivan (indinavir), also a PI, has shown to cause insulin resistance within short duration both in HIV negative and positive patients. The protease inhibitor Viracept has been shown to cause similar side effects, although to a lesser extent. Dr. Raghavan pointed out that PIs are not alone in causing these problems. Sustiva (efavirenz), a non-nucleoside reverse transcriptase inhibitor (NNRTI), has been shown to cause elevated lipid levels, which are detrimental for cardiovascular health. However, Viramune (nevirapine), also a NNRTI, seems to have a beneficial effect on lipids, by increasing high-density lipid (HDL, good cholesterol).

Women and African-Americans tend to have higher good cholesterol, lower triglyceride levels and more fat gain related problems, whereas older individuals tend to have higher bad cholesterol, triglyceride, and glucose levels. Patients taking nucleoside reverse transcriptase inhibitors (NRTIs), particularly Zerit (d4T), and those who are suffering from hepatitis C co-infection are more likely to develop lipoatrophy. Patients who are on ARV therapies for a long duration are also more likely to develop these complications.

Many factors and elements play a role in the development of lipodystrophy and metabolic elevations, including viral load, T-cell count, ctyokine levels, age, diet, exercise and genetic predisposition. Clinical studies are only now being performed to determine their association and hopefully will give us a better understanding of who is at high risk for developing these complications and how to treat them.

HIV Associated Lipodystrophy: Nothing is Certain
Dr. Donald Kotler of St. Luke's-Roosevelt Hospital discussed HIV-related lipodystrophy, with the aim of dispelling myths and leaving the audience with a solid understanding of the condition. Dr. Kotler's message was very similar to that of Dr. Raghavan - nothing is certain. Lipodystrophy continues to confound physicians and researchers alike.

What is lipodystrophy?
In HIV negative populations, past studies of women have shown that people who hold a lot of fat in the upper body and abdominal area seem to be more at risk for heart disease than those whose fat is distributed all over the body. In lipodystrophy, individuals often experience a total body shape change, with rapid fat gain in areas such as the abdomen and breasts, often accompanied by loss of fat in other areas. Dr. Kotler named four key signs and symptoms of lipodystrophy: fat accumulation, fat atrophy (wasting), insulin resistance, and hyperlipidemia (elevated lipid levels in the blood).

So what causes it?
Dr. Kotler feels that ARV therapy is not the sole cause of lipodystrophy. Immune imbalances and other complications of HIV disease could potentially be the culprits. And it's important not to discount other, non-HIV factors that may be the underlying causes in lipodystrophy.

ARV therapy certainly plays some role in the lipodystrophy of HIV+ patients. PIs such as Norvir have caused elevated triglyceride levels in HIV patients. Crixivan has also shown to lead to insulin resistance. NRTIs such as Zerit (d4T) and Retrovir (AZT) can cause elevations in plasma lactate concentrations. Potentially, other factors can also contribute to lipodystrophy and those include gender, family history, ethnicity, race etc. Hepatitis C is another co-factor that could result in insulin resistance.

Potential Treatment Options
Dr. Kotler presented several scenarios for treating the onset of lipodystrophy, and some of its symptoms in HIV+ patients. Changing medications might seem like an obvious solution. Not necessarily, says Dr. Kotler. In clinical trials, Dr. Kotler discovered that switching medications didn't eliminate the problem, only helped to "soften" the symptoms. Perhaps the most effective tool in combating the physical effects of facial lipoatrophy (fat loss) is the use of implants. These synthetic implants are able to hide the fat wasting. However, to date, these implants are not covered by health insurance and, therefore, are extremely expensive. Medications like metformin and rosiglitazone can be used to treat the onset of insulin resistance. Medications such as pravastatin and atorvastatin, which can lower cholesterol by about 20%, may be used to treat high cholesterol levels. And genfibrozil can be used for the treatment of high triglycerides.

Dr. Kotler ran a study aimed to determine the effect of exercise in patients experiencing lipodystrophy. In a small population pool, he discovered that exercise was effective in treating the fat buildup. Human growth hormone (HGH) may be another treatment option. In a study of comparative levels of HGH in patients with HIV, he learned that visceral fat was lowered by use of this growth hormone. However growth hormone can significantly elevate glucose levels. Thus it may be not be a good option for those who are suffering from insulin resistance.

Summary
Lipodystrophy is a common condition in people who are on HAART therapy and also among those taking only NRTIs. There are many factors that may lead to its development, none of which are known with absolute certainty. It is important, however, to treat the body fat changes and metabolic elevations as they can lead to potential disfiguring, diabetes and cardiovascular complications. Finally, hope is not lost if you have lipodystrophy. Despite the lack of information on how this condition arises, many options are available to treat some of the symptoms of lipodystrophy.