Targeted radionuclide therapy could change the whole paradigm used to treat human immunodeficiency virus (HIV), according to one of the most remarkable studies to emerge from the recent Radiological Society of North America (RSNA) annual meeting last month in Chicago.
Ekaterina Dadachova, PhD, professor of radiology, microbiology and immunology at Albert Einstein College of Medicine of Yeshiva University, Bronx, N.Y., and colleagues were able to wipe out residual HIV-infected cells in samples of blood from patients on highly active anti-retroviral drugs using radionuclides conjugated with monoclonal antibodies that specifically seek out the HIV virus.
“Currently the people with HIV have to be maintained on anti-retroviral drugs for life in order not to develop AIDS,” said Dadachova in an exclusive interview with Molecular Imaging. “Potential curative strategy gives HIV patients hope to become HIV free, which would be especially important for young people who have all their lives in front of them.”
The main challenge with antiretroviral therapy is that while it can keep the virus from replicating and make it appear upon testing that a patient is virus-free, it doesn’t kill the viral cells and latent disease can lurk in the shadows and make a comeback. Radioimmunotherapy, potentially with additional drugs that wake up dormant virus in the body, could be the ticket to an actual cure, which would have widespread implications for public health.
“There are certain drugs that can potentially reactivate infected cells and make them visible to the radiolabeled antibody,” said Dadachova. “In the future, radioimmunotherapy might be combined with reactivation agents as parts of an integral strategy to cure HIV.”
The paired treatment could then eradicate both viral particles and infected cells. For this study, the research team provided radioimmunotherapy to 15 HIV-positive patients on antiretroviral drugs. Bismuth-213 combined with the monoclonal antibody mAb2556 was used to hunt down viral cells. The biomarkers were found to bind to antigens on infected cells and deliver a lethal dose of radiation. Results showed clear blood samples with no signs of disease. Human blood brain barrier modeling showed that the drug could even target and kill HIV-infection in the brain without collateral damage.
The next chapter of the research is another study with a larger cohort of HIV-positive patients. Currently, there are plans to conduct the next study in South Africa, but funding could by a challenge.
“We have applied for funding from a medical research council of South Africa,” added Dadachova. “If we are lucky and we get the funding, the clinical trial in HIV patients can start as early as summer of 2014. Simultaneously we are putting together a grant application to NIH to conduct a clinical trial at [Montefiore Medical Center in Bronx, N.Y.]”