The researchers examined 72 individuals in San Francisco—almost all adult males—who had recently tested positive for HIV. Samples of their blood and cerebrospinal fluid were taken and paired. These samples showed that HIV had invaded the central nervous system (CNS) in over 70 percent of the subjects within the first few months of infection. But by the second year of infection, the virus had started replicating itself in the CNS independently from viral populations in the blood in up to 25 percent of these subjects. This process is known as compartmentalization, when a virus sets up shop in a discrete part of the body and begins to reproduce there on its own. HIV compartmentalization in the CNS is difficult to study, Spudich admits, because researchers can’t take brain biopsies of living people—they need to inspect the virus by proxy, by administering spinal taps and collecting cerebrospinal fluid.
The negative consequences of HIV on the central nervous system have been documented for some time. In the late 1980s and early 1990s, when antiretroviral therapy was just being developed, patients with advanced HIV would often experience severe motor and cognitive disorders. In the worst cases, this could mean HIV-associated dementia, which a 1986 study determined could manifest itself as a whole host of symptoms, including apathy, withdrawal, muteness, tremors, incontinence, paralysis, and, in some instances, psychosis. A more-recent study from 2004 reported that HIV could eventually impair “everyday functioning,” making it difficult for people to perform well at work and process verbal information. Although such symptoms have become rarer with improved HIV treatment, they remain prevalent—a 2010 study found that 52 percent of HIV-positive subjects had some neurocognitive impairment.
“There’s also a concern that HIV in the brain could migrate back into the blood, even if it’s been eradicated there,” Spudich says. “That’s the $65 million question. It’s definitely theoretically possible.”
The Yale-UNC study only looked at individuals who hadn’t yet started antiretroviral therapy (except for one subject), so the results may not reflect a large segment of people who’ve been infected with HIV. (According to the World Health Organization, between 35 and 40 percent of those living with HIV were receiving antiretroviral therapy in 2013.) Still, it shows that when HIV-affected people aren’t getting treatment—because they’re unaware of their HIV-status or have chosen not to undergo therapy—the central nervous system can provide an additional reservoir for the virus, possibly leading to neurological damage.
Carl Dieffenbach, director of HIV/AIDS research at the National Institute of Allergy and Infectious Diseases (NIAID), a branch of the National Institutes of Health (NIH), says that in order to find a cure for HIV, scientists will need to consider “tissue-based reservoirs” such as the brain and other organs. He adds that drug cocktails which treat HIV should be designed to penetrate the central nervous system, in order to curtail the virus from taking root there. “This study fits within the continuum of the research that has been done and advances the ball in some important ways,” Dieffenbach says. “Can we develop therapeutic strategies that allow individuals to live happy, normal lives and not transmit the disease? We need to continue to acknowledge that around the globe, 35 to 40 million people are living with HIV.”