In the late 1990s, PHAs using HAART began to report strange changes in body shape. There were also reports of increased levels of sugar, insulin and fatty substances in the blood of these people. These changes increased the risk of non-insulin-dependent diabetes and cardiovascular disease, among other complications. Together, these changes have been called the lipodystrophy syndrome.
The precise cause(s) of these problems is not clear, but their appearance in large numbers of PHAs taking HAART is striking and relatively recent. Although some people have been quick to blame protease inhibitors (PIs) for these problems, recent research suggests that nucleoside analogues, or nukes, such as AZT and similar drugs, may also play a role in the lipodystrophy syndrome.
Researchers in France compared the effect of different combinations of nukes on body fat and insulin production. According to their results, long-term use of nukes appeared to be linked to the loss of fat under the skin. Subjects who used the nuke d4T were more likely to have high levels of triglycerides in their blood, than subjects who did not use d4T.
Researchers enrolled 56 adults with HIV infection who were not taking hormones or appetite stimulants. Some subjects were either taking combinations of nukes or no therapy and were divided into the following three groups:
d4T group — 23 subjects
Combinations used — d4T with 3TC or ddI
AZT group — 16 subjects
Combinations used — AZT with 3TC or ddI or ddC
Control group — 13 subjects
These people did not use anti-HIV drugs
The average CD4+ cell counts of the groups were around 500 cells and viral load in subjects on treatment ranged from 200 to 500 copies. Among subjects not taking therapy, viral load was, on average, higher — around 15,000 copies.
The fat under the skin, which acts as a cushion and insulation, is called subcutaneous fat. In the HIV lipodystrophy syndrome, subcutaneous fat often disappears from the arms, legs and face. In this study, researchers used X-ray or CAT scans to measure levels of subcutaneous fat in the thigh and abdomen of subjects. According to their scans, subjects not taking therapy had the most subcutaneous fat followed by subjects taking AZT. Subjects using d4T had the least amount of this type of fat. Note that the length of time subjects had used anti-HIV therapy was not significantly different between AZT- and d4T-users.
The other type of fat is located deeper inside the body and is called visceral fat. Subjects taking d4T had the highest amount of visceral fat compared to subjects taking AZT or no therapy. This difference in visceral fat levels between the d4T and other groups was also significant.
By observing subjects, researchers found that the following proportion in each group looked as if they had lipo:
Subjects taking d4T were likely to develop lipo faster than subjects taking AZT. Use of other drugs such as ddI or 3TC was not linked to the development of lipo.
As part of a larger, long-term study, data on body weight and composition were collected on subjects three months before they entered the current study. In those three months, subjects receiving d4T lost an average of 2 kg of weight while those taking AZT gained an average of 1.3 kg of weight. This difference between the two groups was significant. No significant changes occurred in muscle mass, despite these changes in weight. This suggests that the weight gained or lost was largely fat.
This study does point out a potential link between d4T use and fat wasting in PHAs. Further studies need to be conducted in larger groups over longer periods to confirm this link. As well, as some PHAs are taking large amounts of antioxidant supplements (vitamins C and E, co-enzyme Q10, lipoic acid and acetyl-L-carnitine) in the hope of protecting themselves from this side effect, research also needs to be conducted on the effect of such products on fat wasting.
REFERENCES:
1. Saint-Marc T, Partisani M, Poizot-Martin I, et al. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS 1999;13(13):1659-1667.
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Copyright © 2001 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca.
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