Radioactive antibodies can seek out and kill HIV-infected blood cells in mouse models. If the same proves true in humans, radioimmunotherapy may provide a new way to combat HIV infection by eliminating viral reservoirs.

The AIDS epidemic is now 25 years old, but there is still no cure for the disease. The treatment of HIV was revolutionized in the late 1990s with the advent of highly active antiretroviral therapy (HAART), drug combinations that target and block HIV enzymes (such as reverse transcriptase inhibitors and protease inhibitors), thus preventing viral replication. HAART has helped to slow disease progression and prolong the lives of many infected with HIV, but also has serious side effects. Moreover, the emergence of drug-resistant HIV strains threatens the continued effectiveness of drug-cocktail treatments like HAART. In addition, although HAART may reduce circulating HIV to undetectable levels, it cannot cure the disease because latently infected cells harbor replication-competent virus.

Now, in new research based on the use of radiolabeled antibodies for treatment of certain cancers, Ekaterina Dadachova of the Albert Einstein College of Medicine (Bronx, NY) and colleagues tested the efficacy of such antibodies in eliminating HIV-infected cells that express viral proteins on their surface. The researchers linked antibodies against the HIV surface glycoproteins gp120 and gp41 with radioisotopes of bismuth (213Bi) and rhenium (188Re), then assayed the ability of the radioactive antibodies to kill HIV-infected cells in vitro (PLoS Medicine, November 2006).

Next, Dadachova's team investigated the same technique, called anti-HIV radioimmunotherapy (RIT), in vivo. They injected SCID mice intrasplenically with HIV-infected human peripheral blood mononuclear cells and then treated them with radioactive antibodies. Ninety-nine percent of the HIV-infected cells were eliminated. Likewise, in SCID mice with human thymic graft implants, RIT resulted in a 2.5-fold decrease in the number of HIV-infected thymocytes. Platelet counts in treated mice suggest that RIT was not associated with acute hematologic toxicity, except at the highest doses of radioactivity.

“Radioimmunotherapy in combination with other drugs may form a basis for a cure [for HIV infection] because [RIT] has the potential to find and eliminate 'viral factories'—the infected cells harboring HIV deep inside organs and tissues,” Dadachova tells Lab Animal. In addition, RIT may be able to eradicate cells infested with drug-resistant virus. Dadachova's team, with an industrial partner, has begun preparation for clinical trials of the therapy, which may begin in less than two years.