February 5, 2001
As reviewed by Dr. Siliciano at this meeting, the major barrier to achieving eradication of HIV from the body are the approximately one million cells that are long lived. There have been attempts to decrease the number of these cells with a few approaches, including antiviral therapy plus IL-2 or an experimental compound called OKT3. However, none of these have been successful in decreasing the size of this pool of cells. This study was designed to use another available medication, called cyclophosphamide, in an attempt to deplete the number of these cells in the body. This drug, used current in treatments for some cancers, can decrease the number of lymphocytes and macrophages (another cell in the immune system) by 95% -- and thus represented a potential approach in the ongoing desire to deplete these cells.
The design was to enroll ten people -- half of whom would take a standard antiviral regimen (d4T, 3TC,a and nelfinavir), and half of which would take this same regimen with the addition of intravenous cyclophosphamide every six weeks. Because this medication can cause nausea and decreases in white cell counts, medications were used to prevent these side effects as much as possible. Lymph node biopsies were done before and after the medications were given as a way to measure the number of these cells.
Despite anti-nausea medication, most of the participants reported nausea and vomiting, and this may have directly influenced the outcome of this study. It is important to note that these antivirals, and specifically nelfinavir, need to be taken with food to be effective. While the entry viral load of all participants was less than 50 copies, the experimental group had evidence of periodic increases in the viral load for the 20-week period of the study intervention. When there is an increase in the viral load, there will be an increase in the reservoir pool as well. Thus, this study reported no change in the reservoir pool despite the intervention.
Clearly, efforts targeted at ways to substantially decrease the reservoir are essential if we are to define ways to truly eradicate HIV from the body. While it may never actually be achieved, studies such as this will continue to see if there might be ways to actually eliminate HIV from the body. While the mood surrounding this type of work is currently pessimistic, the goal is so important that it is necessary to explore any useful ideas.