Highly active antiretroviral therapy (HAART) has improved survival and decreased the chance of death from AIDS-related infections in people who can afford, adhere to, and tolerate the drug cocktails. The last point — tolerate — is important because HAART-users can experience a variety of side effects depending on the combination of drugs taken. One of the more recently recognized side effects is the lipodystrophy syndrome, a term which encompasses the following side effects:
In addition to these physical changes, the lipodystrophy syndrome also involves changes in levels of fats and sugar in the blood:
The precise cause(s) of the lipodystrophy syndrome are not clear. Some doctors suspect that one group of drugs called protease inhibitors (PIs) is responsible for some of the problems with insulin, fat and sugar as well as some of the body shape changes. Other doctors have found that nucleoside analogues (nukes), may play a role in the loss of subcutaneous fat. Some people with HIV/AIDS (PHAs) try to minimize their exposure to PIs by switching to a drug combination based on non-nukes, such as efavirenz (Sustiva) or nevirapine (Viramune), in the hope of reducing their symptoms of lipodystrophy.
Researchers in Spain have been studying the effect of having PHAs switch from a PI-based regimen to one based on nevirapine. According to their results, one year after the switch there were not dramatic reductions in lipodystrophy. However, there were other benefits which we report below.
Researchers recruited 106 HIV positive adults who had signs/symptoms of lipodystrophy and who had been using a PI-based regimen for at least nine months. Subjects were randomly assigned to receive one of the following regimens:
In addition to regular examinations and lab tests, all subjects received special scans called DEXA (dual-energy X-ray absoptiometry) which was used to assess changes in body composition.
Fifty-two subjects were assigned to receive nevirapine and their profile was as follows:
The profile of the 54 subjects who were assigned to receive continued PI-based therapy was as follows:
On average, researchers monitored subjects for one year.
The following side effects developed in the following number of subjects who used nevirapine:
All subjects who developed liver damage while using nevirapine were co-infected with hepatitis C virus (HCV). Interestingly, five out of six subjects who developed this complication were women. A total of six subjects had to stop using nevirapine — two because of rash and four because of liver damage.
The following side effects developed in the following number of subjects who used PI-based regimens:
Nine subjects in the PI group stopped using their anti-HIV medications for the following reasons:
The following number of subjects in each group had their viral load rise above the 400 copy mark while in the study:
These increases in viral load were likely due to HIV becoming resistant to the treatments used by these subjects. The researchers noted that all of the eight subjects had used "multiple" nukes before entering the study, so the likelihood of developing drug-resistance was high. These results are worth bearing in mind by doctors who wish to consider prescribing simpler drug regimens.
By the end of the study, the following proportion of subjects in each group had achieved a viral load below the 50 copy mark:
This difference was not statistically significant.
On average, in each group, there was the following increase in CD4+ cell counts by the end of the study:
There were also increased levels of CD8+ cells, with each group having the following number of extra CD8+ cells by the end of the study:
Again, these differences between the two groups were not statistically significant.
DEXA scans did not detect any major changes in body composition, although subjects who switched from PI-based regimens to nevirapine did tend to experience a decrease in subcutaneous fat.
Among subjects who switched from PIs to nevirapine, a significant decrease in cholesterol and triglyceride levels occurred by the end of the study. No significant changes occurred in this regard among the subjects who continued to use PI-based regimens.
According to the researchers, subjects using nevirapine reported significantly better quality of life than subjects using PIs, mainly because drug regimens became simpler — fewer pills, easier dosage schedules — once subjects switched to nevirapine. Other improvements occurred because side effects from PIs were no longer present. All of these improvements continued to the end of the study.
The researchers noticed that those PHAs who were experiencing fat wasting before entering the study continued to do so regardless of which study regimen they were assigned. It may be that longer periods — more than one year — are required for PHAs to recover from lipodystrophy. It is also possible that continued use of nukes contributes to fat wasting.
REFERENCE
Ruiz L, Negredo E, Domingo P, et al. Antiretroviral treatment simplification with nevirapine in protease inhibitor-experienced patients with HIV-associated lipodystrophy. Journal of Acquired Immune Deficiency Syndrome 2001;27(3):229-236.
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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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