In the late 1990s, people with HIV/AIDS (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 PHAs. 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 the Netherlands have been conducting a study in which subjects were given one of the following regimens:
The purpose of this study was to find out if a PI-only regimen was as effective as a more conventional combination. Because researchers collected information about changes in body shape, results from this study may help in identifying the role that different drugs play in the lipodystrophy syndrome.
Researchers reported results on 175 subjects who were monitored for up to two years. Their profile at the start of the study was as follows:
Both ritonavir and saquinavir were taken at a dose of 400 mg twice daily while d4T was taken in the standard dose. After 12 weeks subjects had the option of "intensifying" their therapy by adding two nukes or a non-nuke to their regimen.
Researchers did not detect any significant differences in CD4+ cell count or viral load between the two study groups.
Doctors reported lipodystrophy in 29 of 175 subjects. On average signs/symptoms of lipodystrophy took about 1½ years to appear after subjects entered the study. The occurrence of lipodystrophy in each group was as follows:
This difference between the two groups was statistically significant, that is, not likely due to chance alone.
When the researchers analysed data from those subjects who had never used anti-HIV drugs the results were similar to those seen in the entire group:
Those subjects who were assigned to receive PIs and a nuke(s) were nearly four times more likely to develop lipodystrophy than subjects who received only PIs.
The researchers noticed that those subjects who entered the study with higher-than-normal levels of cholesterol in their blood were at increased risk for the development of lipodystrophy. As well, those subjects who during the course of the study developed large increases in their cholesterol levels were likely to develop lipodystrophy.
The researchers found that at the start of the study the following factors were not significantly associated with the development of lipodystrophy:
Researchers found that among subjects who developed lipodystrophy, changes in body shape varied. There were cases of fat gain and fat loss (wasting) and cases of both ocurring in the same person. Fat gain occurred in the following proportion of subjects with lipodystrophy:
Fat loss or wasting occurred in the following proportion of subjects with lipodystrophy:
These differences between the two groups, although striking, were not statistically significant. The proportion of subjects with lipodystrophy experiencing both fat gain and fat loss were as follows:
Readers should note that some researchers might say that a weak part of the study was that lipodystrophy was assessed by the subjects' "treating physician" rather than by more "objective" measures such as the following:
Nevertheless, other studies have generally found that the results of physican-based assessment and technical measurements tend to be in agreement when it comes to detecting lipodystrophy.
The results of this study confirm those seen in several others (see TreatmentUpdate 114, "Nukes linked to fat wasting" and TreatmentUpdate 115, "Canadian researchers study 'immune healing'") that found that nukes are likely involved in fat gain/fat loss in HAART-users.
REFERENCE
van der Valk M, Gisolf EH, Reiss P, et al. Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection. AIDS 2001;15(7):847-855.
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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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