Shot in the Dark
Against the Odds, Immune-Based Therapies for HIV Slog Along
The Also Rans: Hollis-Eden's Wonder Drug and Good 'Ole Alpha Interferon
Straddling the boundary between antiretrovirals and IBTs is the approved hepatitis C treatment, pegylated alpha interferon. Alpha interferon appears to have direct antiviral effects and also enhances cell-mediated immune responses in humans. The unpegylated form of alpha interferon was studied for many years as a potential HIV therapy, but eventually abandoned due to underwhelming results. However, the newer pegylated form is now once again being studied as an adjunct to HAART and in the context of treatment interruptions. Another proposed enhancer of cell-mediated immune responses is the DHEA derivative HE2000, but no data has been published on this IBT and many distrust the drug's developer, Hollis-Eden, who have hyped the results from a small South African study without ever managing to get them into the scientific literature.
Immunosuppressive Agents Gone but Not Forgotten
The association between heightened levels of immune activation and HIV disease progression has led some researchers to pursue studies of several drugs that are typically referred to as "immune suppressants." These drugs include cyclosporine, prednisone, hydroxyurea and mycophenylate mofetil. All are approved for other indications, and none of the manufacturers is specifically developing these compounds as IBTs. However, academic researchers continue to evaluate their potential, typically as an adjunct to HAART or in the context of treatment interruptions.
Finally, there is a grab bag of approaches involving infusing CD4 T cells that are isolated from HIV-infected individuals, expanded and in some cases genetically modified in the laboratory and then reinfused as a potential IBT. NeoProbe's Activated Cellular Therapy (ACT) does not involve genetic modification but expands CD4 T cells isolated from the lymph nodes using a technique designed to select the cells secreting HIV-suppressing factors such as beta-chemokines. Despite the publication of intriguing data from a pilot study of the approach, the development of ACT is currently on hold pending identification of commercial partners that might support further research. At least three different biotech companies are attempting to genetically modify CD4 T cells in the lab in order to enhance their resistance to HIV infection, subsequently reinfusing them into the matched HIV-infected donor. A similar approach modifies both CD4 and CD8 T cells in an attempt to improve their ability to restrict HIV replication. Preliminary results from trials of these approaches have shown some limited promise, but it remains uncertain as to whether any of these gene therapy/IBT combinations will eventually enter efficacy trials.
Richard's IBT pipeline report complete with detailed references will be available shortly at the TAG Web site. A more subjective, big-picture evaluation of the IBT pipeline is to appear in the March issue.
This article was provided by Treatment Action Group. It is a part of the publication TAGline.