Antiretroviral therapy may soon be obsolete, as scientists have successfully used immune cells to kick the dormant form of HIV out of its hiding place and destroy it. The findings may soon lead to an HIV vaccine. According to recent estimates, around 1.1 million people in the United States have HIV. With the help of antiretroviral therapy, over half of these people now have a very low level of the virus. This means that they can no longer trasmit it to other people. Antiretroviral therapy can keep HIV in check so well that the virus is near-undetectable in the blood. However, HIV continues to "live" in latent form, so people with it must keep taking the medications to prevent it from flaring up. Antiretroviral therapy can have a host of side effects. These may include gastrointestinal problems, cardiovascular problems, insulin resistance, and bleeding events, as well as effects on bone density, liver health, and neurological and psychiatric health. So, the search for an HIV cure is ongoing. Now, new research may have found a way to "drag" the virus out of its hiding place and neutralize it. The findings may lead to a vaccine that would allow people living with HIV to stop taking antiretroviral medication every day. Senior study author Robbie Mailliard, Ph.D. — an assistant professor of infectious diseases and microbiology at the University of Pittsburgh Graduate School of Public Health in Pennsylvania — and colleagues have published their findings in the journal EBioMedicine. Using an entirely different virus to target HIV Mailliard explains the motivation for their study, saying, "A lot of scientists are trying to develop a cure for HIV, and it's usually built around the 'kick and kill' concept — kick the virus out of hiding and then kill it." He adds, "There are some promising therapies being developed for the kill, but the holy grail is figuring out which cells are harboring HIV so we know what to kick." In the case of HIV, the virus goes latent by hiding itself in the DNA of T helper immune cells. To find out which cells are harboring HIV, the team decided to look at a different virus with a similar behavior that affects 95 percent of people living with HIV: cytomegalovirus (CMV). "The immune system spends a lot of time keeping CMV in check," explains study co-author Charles Rinaldo, Ph.D., chair of the Department of Infectious Diseases and Microbiology at the University of Pittsburgh. "In some people, 1 one out of every 5 T cells are specific to that one virus," adds Rinaldo. "That got us thinking — maybe those cells that are specific to fighting CMV also make up a large part of the latent HIV reservoir." "So we engineered our immunotherapy to not only target HIV but to also activate CMV-specific T helper cells." Dragging HIV out of its hiding place So, the researchers took blood from almost two dozen participants who had HIV but were keeping it in check with antiretroviral therapy. "You have to collect a lot of blood to find T cells latently infected with functional HIV in people on [antiretroviral therapy] — it could be as few as 1 out of every 10 million cells," explains first study author Jan Kristoff. The researchers also isolated another type of immune cell called dendritic cells. Mailliard describes these cells using a sports analogy; they are the "quarterbacks" of the immune system, he says, as "they hand off the ball and dictate the plays, telling other immune cells where to go and what to fight." In previous studies, scientists used dendritic cells to "make" the immune system kill HIV. Before this study, however, nobody had used them to drag the latent HIV out of its hiding place. In this research, Mailliard and his team designed "antigen-presenting type 1-polarized, monocyte-derived dendritic cells" (MDC1). They engineered these MDC1 cells to look for and activate CMV-specific T helper cells in the hope that these CMV-specific cells would also hide latent HIV. Then, the team added MDC1 back to the T helper cells containing latent HIV. This successfully reversed the latency. The virus had to leave its hiding place, making it vulnerable and easy to kill. "Without adding any other drug or therapy," explains Mailliard, "MDC1 were then able to recruit killer T cells to eliminate the virally infected cells." "With just MDC1, we achieved both kick and kill — it's like the Swiss Army knife of immunotherapies. To our knowledge, this is the first study to program dendritic cells to incorporate CMV to get the kick, and also to get the kill." - Robbie Mailliard, Ph.D. Mailliard and his colleagues are now trying to test MDC1 in human clinical trials. Source
