Some people with HIV/AIDS (PHAs) who take combination anti-HIV therapy that includes a protease inhibitor (PI) have developed the following side effects:
Collectively, these signs/symptoms have been called the lipodystrophy syndrome. At first there was a tendency to place the blame for all of these problems on PIs. However, as doctors have spent more time studying these issues, it has become clear that there is no one cause for the many changes that are part of the lipodystrophy syndrome. Indeed, there may be several syndromes occurring at the same time and the role played by different types of anti-HIV drugs is still not quite clear. Nevertheless, some PHAs may wish to switch from a PI-based regimen to a combination based on a non-nucleoside analogue, or non-nuke, such as nevirapine (Viramune) or efavirenz (Sustiva).
Doctors in Spain enrolled 20 subjects who complained of changes in body shape since they had started taking PI-based regimens. All subjects had low HIV levels — below the 200 copy mark — and had their PI replaced with efavirenz. In general, six months after the switch viral load and CD4+ cell counts remained stable. Some aspects of the lipodystrophy syndrome changed while others did not. The possible reasons for this are discussed in the report below.
Researchers enrolled 11 males and nine females whose profile was as follows:
At the start of the study, before switching medications, all subjects complained of fat redistribution with some experiencing one or more of the following signs:
As well, subjects had lost fat in their arms, legs and buttocks. All subjects switched their medication "backbone" from one based on a PI to one based on efavirenz. They were monitored for at least six months.
Results — waist size, fat
Overall, body weight did not change, even six months after subjects switched therapy. Subjects did lose weight in their abdomen as their waist became smaller, but this trend did not become statistically significant.
Ultrasound scans of fat under the skin (subcutaneous fat) in the abdominal area did not detect any decrease six months after the medication switch. However, 11 subjects reported that they felt their appearance had improved after the switch.
Results — viral load and CD4+ cells
At the start of the study, before subjects switched medications, levels of HIV in the blood were as follows:
Six months later, after switching from a PI to efavirenz, virus levels in blood samples were as follows:
The one subject whose viral load rose above the 200 copy mark to 565 copies had to stop taking efavirenz.
Before the switch, CD4+ counts averaged about 280 cells. After the switch, counts rose slightly to 363 cells — this change was not statistically significant.
Levels of lipids — triglycerides and "bad" cholesterol or LDL (low density lipoprotein) — that were higher-than-normal at the start of the study decreased significantly six months after subjects switched to efavirenz. Levels of "good" cholesterol or HDL (high density lipoprotein) and sugar (glucose) in the blood did not change after six months of efavirenz use.
Five subjects developed minor efavirenz-related side effects, including the following:
These symptoms cleared after one month. Three other subjects developed severe side effects including the following:
These side effects were severe enough that subjects had to stop taking efavirenz and replace it with nevirapine. A few days after switching to nevirapine these symptoms cleared.
It is disappointing that the subcutaneous fat — the fat under the skin that acts as a cushion and insulation — did not reappear after subjects had switched therapy, because its return would also improve the appearance of PHAs with lipodystrophy, or lipo. Researchers are still trying to understand the cause(s) of the lipodystrophy syndrome. It is not clear if the loss of this type of fat is permanent. Loss of subcutaneous fat has been linked to the use of nucleoside analogues, or nukes, such as AZT and related drugs. Therefore, continued use of these drugs may impair the return of subcutaneous fat. There are several studies in which subjects have taken only PIs or a combination of PIs and non-nukes. Doctors in several centres are measuring levels of subcutaneous fat in subjects on these regimens to find out if they have experienced loss of this type of fat. Results from these studies should be available at major AIDS conferences in 2002.
REFERENCE:
1. Martinez E, Garcia-Viejo MA, Blanco JL, et al. Impact of switching from human immunodeficiency virus type 1 protease inhibitors to efavirenz in successfully treated adults with lipodystrophy. Clinical Infectious Diseases 2000;31(5):1266-73.
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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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