For the last decade-plus, retroviral therapies have kept HIV in check for many of the 30 million people infected with the virus worldwide. These drugs can reduce a person's blood viral load to undetectable levels—and yet, it remains the case that people must continue with the therapy in order to keep the virus at bay. Where and how is the virus hiding in the interim? A study conducted by scientists at the University of Michigan suggests that the virus may be lurking in bone marrow, in a particular type of cell. They hope that by pinpointing the where and how of the virus' hiding place, they may be able to get closer to the ultimate goal of killing it off entirely.
The study's authors characterize their project in terms of a next step in treating HIV. "Antiviral drugs have been effective at keeping the virus at bay. However once the drug therapy is stopped, the virus comes back," says senior study author Kathleen L. Collins, M.D., Ph.D., associate professor of internal medicine, microbiology and immunology at the U-M Medical School. "Currently people have to take antiviral drugs for their entire life to control the infection," she says. "It would be easier to treat this disease in countries that don't have the same resources as we do with a course of therapy for a few months, or even years. But based on what we know now people have to stay on drugs for their entire life."
That's where Collins research may prove helpful. Her study, the findings of which appear online in the journal Nature Medicine, examined tissue samples taken from the bone marrow of HIV+ people who had undergone at least six months of successful antiviral therapy. While antiviral medications may prevent the virus from infecting new cells, "they don't get rid of cells that contain the virus and have potential to make new viral particles," Collins said. So it is troubling that the researchers found that not only was HIV lurking in the bone marrow cells, despite its invisibility in blood cells, but it was lurking in specific types of cells that are progenitors (basically, parent cells) of blood cells. This is a particularly dangerous place for the virus to hide, Collins says. "Our finding that HIV infects these cells has clear ramifications for HIV disease because some of these cells may be long-lived and could carry latent HIV for extended periods of time," she explains. "These HIV cell reservoirs can be induced to generate new infections." Let an HIV infection go active by ceasing antiviral therapy and the virus will both kill the parent cell and let loose viral particles into new cells.
One can't simply kill off all of the type of bone marrow cells that become infected, since the body needs them in order to survive. So what can anyone do with this information? Collins suggests a targeted next step. "Ultimately to cure this disease, we're going to have to develop specific strategies aimed at targeting these latently infected cells." She hopes, she says, that there may be ways of treating only these time-bomb bone marrow cells.
Were this treatment developed, it still would not address all of the places in the body where HIV may be hiding from retroviral therapies. But it would signal a new way forward, as the urgency for finding a cure rather than a treatment is a global goal of HIV research. As Collins says, "Drugs now available are effective at treating the virus, making HIV more of a chronic disease than a death sentence. This has made a huge impact in quality of life, however only 40 percent of people worldwide are receiving antiviral drugs and unfortunately that means that not everybody is benefiting."