It worked for treating cancer; now researchers have found they can send dollops of lethal radiation directly into HIV-infected cells using radioactive antibodies. So far the technique only works in mice, but investigators hope they can extend their proof-of-concept to a treatment capable of destroying all of the infected cells in a person's body under some circumstances. "Twenty-five years from the start of the epidemic, HIV is still an incurable disease--something completely different needs to be done to completely eradicate it," says nuclear medicine specialist Ekaterina Dadachova of the Albert Einstein College of Medicine in New York City, first author of a report published November 6 in PLoS Medicine that describes the results.
Antiretroviral drugs keep HIV at bay but do not kill the virus. Instead they stop it from reproducing and let the immune system clear out infected cells. Dadachova and her colleagues reasoned they could kill these cells directly and with minimal harm to the rest of the body if they could make radioactive isotopes cluster around the cells. Researchers have already found success against certain cancers by attaching radioactive isotopes to antibodies that seek out tumor cells. So the team linked radioactive bismuth 213 and rhenium 188 to antibodies designed to stick to two HIV proteins (gp41 and gp120) displayed on the surface of infected cells. To see if the antibodies would home in on the offending cells, they injected the compound into mice that contained human blood cells infected with HIV. The compound appeared to work safely: the treated mice had less than half the quantity of infected cells that their untreated counterparts did, and the animals suffered collateral damage to healthy blood cells only at the highest antibody dose, the group reports. Dadachova says the team is working with a pharmaceutical company to see if a clinical trial is warranted.
In principle, the technique could supplement antiretroviral therapy for a brief time, especially very early in an infection before the immune response has kicked in, says AIDS vaccine researcher David Montefiori of Duke University. "This is the type of treatment technology that gives one hope it might be possible to eliminate the virus," he says. Major uncertainties remain, though. As HIV infections progress, some infected cells go dormant and do not cover themselves in the proteins, or antigens, that antibodies recognize. Treatment, let alone cure, is only possible, Montefiori says, "if this therapy is effective in killing HIV -infected cells in humans, as it was in mice, and if the latently infected cells can be induced to express viral antigens. Those are two big if's."