When HIV Infects the Brain

A new study reports that the virus can infiltrate the central nervous system within months of infection.

Just over 30 years ago, an international group of scientists discovered the HIV virus. While much progress has been made since the early days of the epidemic (in terms of awareness, prevention, and treatment), HIV and AIDS remain a leading cause of death worldwide, and rank as the number one cause of death both in Africa and among women of reproductive age. A cure has yet to be found, though every so often headlines contain the word “hope.”

A study published Thursday in the online journal PLOS Pathogens gives reason for pause, showing that HIV can behave more insidiously than previously seen. Researchers at the Yale School of Medicine and the University of North Carolina have found that the virus can settle in people’s brains as early as four months after infection. In turn, HIV in the brain can genetically mutate—differentiating itself from the type circulating in the blood—which means that certain drugs used to treat the virus may not work as well in the central nervous system as they do in other parts of the body. Over time, untreated HIV can cause negative neurological and mental-health effects, such as brain swelling and a form of dementia.

“Most people have paid attention to HIV as a disease of the immune system that causes immune-cell damage,” says Serena Spudich, senior author of the paper and a neurologist at Yale. “The implication [of our work] is that there’s a specific infection of the brain rather than HIV just being carried in the blood and passing through the brain. This can cause subtle cognitive symptoms in the long-term.”

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.”

That statistic—and the human suffering behind it—is precisely why non-profit groups still advocate for HIV prevention and awareness more than three decades after the virus was first identified.

Michael Kaplan, president and CEO of AIDS United, a national organization that focuses on grant-making, capacity building, and policy in the United States, says that although HIV prevention has vastly improved since the previous century, barriers to healthcare like cost, education, and the stigma associated with seeking treatment for HIV continue to pose substantial challenges. Yet with about 30 drugs available to manage the disease today, HIV is no longer the death sentence it was once perceived to be: a 20-year-old infected with HIV (living in a high-income country) who starts antiretroviral therapy immediately can expect 55 years of additional life, Kaplan says, citing data from a 2014 report by UNAIDS. He also points to an international study published in 2011 and sponsored by NIAID, which found that early antiretroviral therapy reduced the sexual transmission of HIV in straight couples by 96 percent.

It’s easy to take these glowing numbers and declare that the end of HIV/AIDS is in sight. But, as the Yale-UNC study shows, there’s a lot about the disease that remains unknown. Mitchell Warren, executive director of AVAC—an HIV-advocacy organization that operates globally—says science and advocacy need to be linked in order to overcome the HIV/AIDS epidemic. There’s great hope for a cure, he adds, but ultimately people must be able to access it.

“Science without advocacy and advocacy without science are two relatively inefficient mechanisms,” Warren explains. “That was true in the past, and it’s still true but even harder today. We shouldn’t be under any illusions about that.”