The Battle of the Bulge

Lipodystrophy, the abnormal redistribution of body--fat stores, is found in 40% to 50% of U.S. HIVers, and it remains one of the disease's problematic outcomes. Its two principal components are lipoatrophy, the loss of fat in the limbs and face, and lipoaccumulation, the increase of fat within the abdomen and around the neck and chest. These may seem like opposite conditions, but both can occur in some patients. Initially protease inhibitors were seen as the cause of increased intra-abdominal fat, called visceral adipose tissue. We now know that this effect can be seen in patients who've never used protease inhibitors. With lipoatrophy there is a clearer association with the use of Zerit and AZT. But increased risk for either form of lipodystrophy includes duration and severity of HIV infection, lowest CD4 count, length of treatment, prolonged delay before treatment, and age. While lipoatrophy can be stigmatizing, it has no significant medical implications. Efforts to improve limb fat with insulin--sensitizing agents have had little success, but facial fillers can improve the appearance of people struggling with cheek--fat loss. Lipoaccumulation, though, is associated with insulin resistance, elevated lipids, and increased risk of heart disease. In extreme cases there can be painful abdominal distension and restricted breathing. Rigorous exercise and dieting'along with standard medications'can help reduce insulin resistance and lipid levels but have not had much effect on reducing intra-abdominal fat. Drugmakers had high hopes for two drugs as treatments for lipoaccumulation. Serostim was denied approval in July; but a new one is in the pipeline for approval. During studies of recombinant human growth hormone to treat HIV wasting, though, researchers have found some decrease in intra-abdominal fat. In one trial of recombinant human growth hormone (somatropin or Serostim), participants were given either a placebo or a four-milligram dose of growth hormone daily for 12 weeks. The group on Serostim was then reduced to a maintenance dosage of two milligrams every other day for another 24 weeks. After the first 12 weeks, intra-abdominal fat decreased 24% in the group taking recombinant human growth hormone. Mild side effects included edema and joint and muscle pain. Blood-sugar levels increased initially but then returned to normal. There was also loss of limb fat, which slowly returned to normal at the end of the 24--week maintenance period. On the every--other--day maintenance dose, about 40% of participants regained at least 50% of abdominal fat they had lost; this was considered a significant positive result. Because the surge of growth hormone that occurs in the body after it has been injected can have severe cardiovascular implications, such as disrupting glucose metabolism and elevating triglycerides, researchers have turned their attention to growth--hormone releasing factor. The advantage is that the releasing factor re--creates the natural pulsatile release of growth hormone and allows the regulatory feedback mechanism in the body to control the growth hormone effect. At this year's Conference on Retroviruses and Opportunistic Infections, Steven Grinspoon reported on a Phase III trial of TH9507, a synthetic growth hormone releasing factor made by Theratechnologies. At the end of a placebo--controlled 26--week trial with 412 participants, intra--abdominal fat decreased 15% in the group given TH9507 versus a 5% increase in the group who had received a placebo. Limb fat increased slightly in both groups. Better yet, the TH9507 group showed a decrease in total cholesterol and triglycerides and an increase in 'good' HDL cholesterol; in the placebo group triglycerides rose and HDL levels fell. In addition, there were no significant changes in insulin and glucose levels in the TH9507 group. Muscle aches and skin rash were the most common side effects. If synthetic growth hormone releasing factor eventually makes it to market, we may have our first victory in the battle of the bulge. Bowers is board-certified in family practice and is a senior partner with Pacific Oaks Medical Group, one of the largest U.S. practices devoted to HIV care.