Important note: Information in this article was accurate in June 2000. The state of the art may have changed since the publication date.
Protease inhibitors (PI) have made a huge impact on the AIDS pandemic in North America by prolonging the survival of people with HIV/AIDS (PHAs). These drugs are associated with several side effects including the following:
Why these changes occur is not clear, and they may be triggered by several factors. PHAs who experience fat redistribution while taking PI-based regimens may not like their new body shape. Reports of small numbers of PHAs switching from a PI-based regimen to one based on a non-nuke such as efavirenz or nevirapine suggest that long-term side effects may not be as bothersome. Researchers in Spain conducted a study on 138 HIV-positive subjects to find out the risks and benefits of replacing PIs with nevirapine. According to their results, this switch in therapy provided the same benefit as before. Even so, there are some issues relating to the interplay between the immune system and protease inhibitors that readers ought to consider before switching. These issues are highlighted later in this report.
Doctors recruited 138 subjects (11% female, 89% male) for their study. Before entering the study no subject had used non-nukes (delavirdine, efavirenz, nevirapine) and all had a viral load below the 50-copy mark for the past six months. On average, all subjects had been receiving a PI and two nukes (nucleoside analogues: AZT and similar drugs) for about 18 months. The average CD4+ count was 641 cells.
Researchers randomly assigned 104 subjects to receive nevirapine instead of a PI and the remaining 34 subjects to continue their existing PI-containing regimen. The researchers released their analysis after six months of monitoring their subjects.
Doctors found that viral load was more likely to rise to detectable levels among subjects who used a protease inhibitor than among those who switched to nevirapine. The proportion of subjects with detectable viral load by the sixth month of the study was as follows:
This increase in viral load among subjects taking PI was, according to the researchers, "due to either toxicity or poor compliance" in 90% of cases. Among subjects who switched to nevirapine, such problems only occurred in 22% of cases. This difference was statistically significant, that is, not likely due to chance alone.
The researchers stated that levels of lipids such as cholesterol and triglycerides in the blood of all subjects tended to be near the normal range. They also noted that after six months of taking nevirapine, about 50% of subjects "had at least a partial [improvement] in their body shape abnormalities, but none of those continuing to use PIs showed any improvement."
There were no statistically significant differences in cell counts between those subjects who switched to nevirapine and those who continued to use PIs. Researchers did find the following trends in the two groups:
One possible reason for the trend in higher CD4+ counts among PI-users is that this group of drugs interacts with the immune system in different ways from non-PI drugs. Indeed, researchers in Ottawa have found that PIs stop CD4+ and CD8+ cells in HIV+ subjects from committing suicide or apoptosis. As well, there have been cases of "discordant" responses in which PHAs taking PI-therapy experience increased CD4+ cell counts despite rising viral load.
The six-month results from this trial are promising, although results from a longer study would have been useful. As well, more sophisticated and detailed measures of body fat distribution would have been helpful in producing an objective analysis of body shape changes in subjects taking nevirapine.
1. Barreiro P, Soriano V, Blanco F, et al. Risks and benefits of replacing protease inhibitors by nevirapine in HIV-infected subjects under long-term successful triple combination therapy. AIDS 2000;14(7):807-812.
2. Phenix BN, Angel JB, Mandy F, et al. Decreased HIV-associated T cell apoptosis by HIV protease inhibitors. AIDS Research and Human Retroviruses 2000;16(6):559-567.
3. Goldberg B and Stricker RB. HIV protease and the pathogenesis of AIDS. Research in Virology 1996;147:375-379.
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