Comprehensive HIV Services Planning and Advisory Council
News
November 22, 2010
HIV Infection Shouldn’t Rule Out Kidney Transplantation
People with HIV who received a kidney transplant did almost as well as HIV-negative people of a similar age and better than older HIV-negative transplant recipients, according to a study published November 18 in The New England Journal of Medicine and reported by aidsmap.com.
Despite the significant health benefits of antiretroviral (ARV) therapy, people with HIV remained at an increased risk for end-stage kidney disease compared with HIV-negative people. Early in the epidemic, when less was known about HIV and before the introduction of potent combination ARV therapy, doctors refused to conduct kidney and liver transplants in HIV-positive people. This is because immune suppressive drugs are a used to keep people from rejecting the new organ, and such therapy can potentially increase a person’s risk of worsening his or her HIV disease through the loss of infection fighting CD4 cells.
After ARVs became widely used, and their ability to preserve health and CD4 counts were known, transplant experts reversed their earlier position and began conducting transplants in people with HIV with kidney and liver disease. Subsequently, small studies have indicated that people with HIV who receive transplants do about as well as HIV-negative people, but researchers have continued to study the procedures in hopes of learning how to improve the safety and efficacy of transplants in HIV-positive people.
To more thoroughly understand transplant success in people with HIV, Peter Stock, MD, PhD, from the University of California in San Francisco, and his colleagues tracked 150 HIV-positive people who received kidney transplants between 2003 and 2009 at one of 19 transplant centers in the United States. The average post-transplant follow-up time was 1.7 years, though a significant proportion were followed for three or more years.
At one year following the transplants, only 5 percent died, and just 10 percent suffered organ rejection. After three years of follow-up, 12 percent had died and 27 percent had rejection of their transplanted kidney. These rates are only moderately lower than in HIV-negative people of a similar age, and are actually higher than transplant success rates in HIV-negative people older than 65.
“Kidney transplantation is highly feasible in HIV-infected recipients,” commented the investigators, who also acknowledge that further study and refinement of the use of anti-rejection, immune-suppressive drugs is warranted to improve success rates without putting people at risk for HIV disease progression.
November 19, 2010
Protein Discovery Helps Explain the Body’s Failure to Kill HIV
Researchers at Rush University Medical Center in Chicago have discovered a protein produced by HIV that keeps infected cells from signaling the immune system that they are harboring the virus and should be killed. These data, which suggest a new target for HIV drugs, were published online October 18 in the journal Cell Host & Microbe and are discussed in a release available at EurekAlert.
Among the most powerful tools in the immune system’s toolbox for killing infected or defective cells are natural killer (NK) cells. They are unlike HIV-specific CD8 cells, which require a lot of stimulation by other parts of the immune system before they can go into action. NK don’t require virus-specific stimulation before they can recognize and kill infected cells. Yet, for reasons not fully understood, they don’t work the way they should against HIV.
Given the potency of NK cells, and their potential to run amok and kill healthy cells, they must first encounter three different types of proteins on the surface of a potentially infected cell. First, an infected cell needs to express a type of receptor called a major histocompatibiliy (MHC) receptor, which indicates that the cell belongs to the person. The NK cell must also encounter a stimulatory molecule and a costimulatory molecule on the target cell’s surface. If all three of these molecules are present and bind to the corresponding NK cell receptors, then the NK cell will release a chemical that degrades the infected cell.
During the past two decades, immunologists have investigated how NK cells interact with HIV-infected cells, but researchers have long been baffled by a key finding. While the kinds of cellular proteins that are supposed to flag the cell for destruction do get made during the HIV replication process and travel to the surface of the cell, NK cells still fail to recognize and kill them.
It turned out that yet another type of protein called Natural killer T-cell and B-cell Antigen (NTB-A) is also needed at the cell’s surface to alert NK cells that the cell is infected and needs to be destroyed. In the case of HIV, the NTB-A didn’t make it to the surface. Researchers, however, found that HIV did not directly suppress the NTB-A. So why didn’t it make it to the surface to alert the killer cells?
Ankur Shah, PhD, from Rush University, and his colleagues now think they know the answer. Shah’s team found that an accessory protein made by HIV, called Vpu, keeps NTB-A from reaching the cell’s surface.
Shah’s team proved this by altering the Vpu protein made by HIV in cells in test tubes and then observing what happened when they added NK cells. The NK cells were 100 times as likely to recognize and kill cells infected with HIV that produced the defective Vpu protein than those infected with HIV that produced the normal Vpu protein.
“With this information, we now have a major new target for drug therapies that could potentially stop HIV [by targeting Vpu] and allow the body’s natural killer cells to do what they are designed to do—protect the body from this lethal virus,” said Edward Barker, PhD, associate professor of immunology and microbiology at Rush University and the lead author of the study.
