For some people, highly active antiretroviral therapy (HAART) has resulted in the remission of AIDS symptoms and prolonged survival. Yet, despite HAART's ability to drive down viral load to five copies or fewer, production of HIV continues. This low-level production of HIV allows the infection to persist and forces people with HIV/AIDS to remain on therapy.
The cells that act as a reservoir for HIV appear to be latently infected CD4+ T-cells. In this case, the cells are alive, but HIV lies asleep inside them. Various things can stimulate these cells, causing the virus to awaken and the cells to begin producing more copies of HIV. Included in these immunological stimulants are:
In an effort to reduce the number of latently infected T-cells, researchers are designing therapies meant to seek out and destroy HIV-infected cells. Many of these therapies are made by joining antibodies to poisons. The resulting product is called an immunotoxin (IT). One possible way to clear the body of residual HIV appears to lie in attacking T-cells that quietly harbour HIV with ITs.
In one series of lab experiments, researchers in Texas were able to wipe out all but 1.5 per cent of cells latently infected with HIV. The cells killed were CD4+ memory cells. Memory cells are immune cells that have successfully defeated a disease-causing agent in the past. When exposed to the disease in question again, these cells "remember" how to fight it. Despite the loss of CD4+ memory cells in these experiments, other cell types appeared to remain unharmed and fully functional. Successive treatment with IT eventually eliminated cells that produce HIV.
An important issue is the safety and effectiveness of this therapy in people whose level of HIV has been suppressed with HAART. Several concerns about IT therapy:
Research is under way to refine and test IT therapy in HIV-positive humans. The next issue of TreatmentUpdate will feature results from such experiments.
1. Dornadula G, Zhang H, VanVitert B, et al. Residual HIV-1 RNA in blood plasma of patients taking suppressive Highly Active Antiretroviral Therapy. Journal of the American Medical Association 1999;282:1627-1632.
2. McCoig C, Van Dyke G, Chou C-S, et al. An anti-CD45RO immunotoxin eliminates T cells latently infected with HIV-1 in vitro. Proceedings of the National Academy of Sciences USA 1999;96:11482-11485.
3. Ostrowski MA, Chun T-A, Justement SJ, et al. Both memory and CD45RA+/CD62L+ naive CD4+ T cells are infected in Human Immunodeficiency Virus Type 1-infected individuals. Journal of Virology 1999;73(8)6430-6345.
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