HIV Cure Possible Using Radioimmunotherapy

The study’s findings were presented at the annual meeting of the Radiological Society of North America (RSNA), held December 1–6, 2013, in Chicago (IL, USA). Highly active antiretroviral therapy (HAART) has changed the outlook for patients infected with HIV by inhibiting the replication of the virus in the body. However, in spite of the success of HAART in effectively decreasing the burden of HIV, scientists believe reservoirs of latently infected cells persist in the body, preventing the possibility of a permanent cure.

“In an HIV patient on HAART, drugs suppress viral replication, which means they keep the number of viral particles in a patient’s bloodstream very low. However, HAART cannot kill the HIV-infected cells,” said the study’s lead author, Ekaterina Dadachova, PhD, professor of radiology, microbiology and immunology at Albert Einstein College of Medicine (Bronx, NY, USA). “Any strategy for curing HIV infection must include a method to eliminate viral-infected cells.”

Dr. Dadachova and coworkers of the study administered RIT to blood samples from 15 HIV patients treated with HAART at the Einstein-Montefiore Center for AIDS Research. RIT, which has typically been employed to treat cancer, uses monoclonal antibodies—cloned cells that are recruited by the immune system to identify and neutralize antigens. Antigens are foreign objects such as bacteria and viruses that trigger an immune response in the body. The antibody, designed to recognize and bind to a specific cell antigen, is paired with a radioactive isotope. When injected into the patient’s bloodstream, the laboratory-developed antibody travels to the target cell where the radiation is then delivered. “In RIT, the antibodies bind to the infected cells and kill them by radiation,” Dr. Dadachova said. “When HAART and RIT are used together, they kill the virus and the infected cells, respectively.”

Dr. Dadachova’s team combined the monoclonal antibody (mAb2556) designed to target a protein expressed on the surface of HIV-infected cells with the radionuclide bismuth-213. The researchers discovered that RIT was able to kill HIV-infected lymphocytes earlier treated with HAART, decreasing the HIV infection in the blood samples to undetectable levels. “The elimination of HIV-infected cells with RIT was profound and specific,” Dr. Dadachova said. “The radionuclide we used delivered radiation only to HIV-infected cells without damaging nearby cells.”

An important part of the study assessed the ability of the radiolabeled antibody to reach HIV-infected cells in the brain and central nervous system. Using an in vitro human blood-brain-barrier model, the researchers revealed that radiolabeled mAb2556 could cross the blood brain barrier and destroy HIV-infected cells without any overt damage to the barrier itself.

“Antiretroviral treatment only partially penetrates the blood brain barrier, which means that even if a patient is free of HIV systemically, the virus is still able to rage on in the brain, causing cognitive disorders and mental decline,” Dr. Dadachova said. “Our study showed that RIT is able to kill HIV-infected cells both systemically and within the central nervous system.”

Clinical trials in HIV patients are the next phase for the RIT therapy, according to Dr. Dadachova.

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