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Immune-Based Therapies Still Languish

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tagline 2003 June

By richard Jeffreys

The field of immune-based therapies (IBT) offers hope that researchers can develop strategies allowing people with HIV to delay or interrupt antiretroviral therapy, ideally reducing drug resistance problems and side effects due to HAART (highly active antiretroviral therapy). In theory, immune-based therapies could offset the damage to the immune system done by HIV, improve the quality and strength of the immune response, or help the immune system control HIV without antiretrovirals. Yet while we have nearly 20 antiretroviral drugs that attack HIV replication, we have no approved therapies directed at the immune system.

Despite the potential for changing HIV treatment, only one immune-based therapy, interleukin-2, is currently in phase III trials—and the results from these SILCAAT and ESPRIT trials won’t be available for years. Therapeutic vaccines, designed to improve the immune system’s ability to control HIV in people who are chronically infected, are still in the early stages of development (with the exception of the Phoenix-like tenacity of Remune). The therapeutic vaccines furthest along are being researched in small studies designed to determine safety and measure changes in the immune response to HIV.

At this year’s Retrovirus conference, results from a small German study of an HIV-nef based vaccine as well as results from two French ALVAC based vaccine studies failed to generate much enthusiasm.

Other European researchers looked at using mycophenolate mofetil (MMF), an immunosuppressant used to prevent organ rejection in kidney, liver, and heart transplants, to see if it might indirectly prevent HIV replication potentially reduce the viral reservoir of HIV-infected cells by inhibiting the proliferation of CD4 cells (similar to the proposed mechanism of action for hydroxyurea). Results from these studies were mixed and inconclusive. Interestingly, the AIDS Clinical Trials Group in the U.S. is currently studying MMF in combination with DAPD (amdoxovir), an experimental nucleoside analogue, in treatment-experienced patients.