appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN).
The study’s investigators also developed a simple urine test to diagnose such infections.
Meanwhile, researchers have used radioimmunotherapy (RIT) to destroy remaining human immunodeficiency virus (HIV)-infected cells in the blood samples of patients treated with antiretroviral therapy, offering the promise of a strategy for curing HIV infection. Results of the study were presented at the annual meeting of the Radiological Society of North America (RSNA).
HIV is a common cause of kidney failure, and because of this, approximately 900 HIV-infected patients start dialysis each year in the United States. Kidney transplantation has recently become a therapeutic option for these patients, and the survival rate of HIV-infected transplant recipients with undetectable HIV in the blood is similar to that of non-HIV-infected transplant recipients. For unknown reasons, however, organ rejection is more common in HIV-infected transplant recipients.
To investigate this issue, Guillaume Canaud, MD, PhD (Necker Hospital, in Paris, France) and his colleagues assessed all 19 of HIV-positive patients in their center who received kidney transplants between June 1, 2006, and October 31, 2011. Genetic analyses demonstrated that HIV infection occurred in 68% of the HIV-positive recipients’ new organs even in the absence of any detectable HIV in their blood.
Biopsy experiments revealed two different forms of infection. In the first case, podocyte cells - which constitute the barrier through which blood is filtered in the kidneys - are the main target of HIV, and infection is associated with certain clinical signs of kidney dysfunction. In the second case, HIV infects tubular cells within the kidney, with fewer clinical manifestations.
The researchers also developed a new and simple urine test to detect HIV infection in the kidneys, which could be a promising non-invasive method for diagnosing problems in HIV-positive transplant recipients.
“This study is going to change the way of thinking of nephrologists and will certainly modify the approach of kidney transplantation in HIV patients, giving new hope to patients,” said Dr. Canaud.
According to an accompanying editorial by Peter Stock, MD (University of California, San Francisco), the noninvasive urine test that detects early HIV-1 infection will help clinicians identify donor and recipient factors associated with recurrent HIV kidney disease. “It is less clear what intervention may control the reinfection, although identification of donor and/or recipient factors associated with early reinfection may provide some clues,” he wrote.
Highly active antiretroviral therapy (HAART) has transformed the outlook for patients infected with HIV by suppressing the replication of the virus in the body.
However, despite the success of HAART in effectively reducing the burden of HIV, scientists believe reservoirs of latently infected cells persist in the body, preventing the possibility of a permanent cure.
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, Ph.D., professor of radiology, microbiology and immunology at Albert Einstein College of Medicine in the Bronx, N.Y. “Any strategy for curing HIV infection must include a method to eliminate viral-infected cells.”
to blood samples from 15 HIV patients treated with HAART at the Einstein-Montefiore Center for AIDS Research.
RIT, which has historically 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 like bacteria and viruses that stimulate 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.
(mAb2556) designed to target a protein expressed on the surface of HIV-infected cells with the radionuclide Bismuth-213.
The researchers found that RIT was able to kill HIV-infected lymphocytes previously treated with HAART, reducing 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.”