It’s been 36 years since HIV — the virus that causes AIDS — was discovered by scientists. Since then, a cure has eluded researchers, but thanks to antiretroviral medications, HIV is no longer the death sentence it was in the 1980s and 1990s.

While a vaccine and curative therapies are still being investigated, research at the University of Nebraska–Lincoln has now turned to the disease and its treatments’ long-term effects, such as the neurological deficits that are especially prevalent among injection-drug users.

“People are living longer but showing signs of other disease, and we are trying to understand the mechanisms of the disease in an aging population,” Charles Wood, Lewis Lehr/3M University Professor biological sciences and biochemistry, said. “We will be studying the effects of drug use on neurological impairments in HIV-infected individuals.”

Wood is joining forces with Kirk Dombrowski, John Bruhn Professor of Sociology and director of the new Rural Drug Addiction Research Center, to lead an investigation into this phenomenon with funding from a five-year, $3 million grant from the National Institute of Drug Abuse.

The team will examine the causes of HIV-associated neurological disorders, which are more common among injection-drug users even when successful treatment keeps the HIV virus undetectable in the bloodstream.

“The big question is: What is it about drug users that, even though we can get their viral load down, this still keeps happening?” Dombrowski said. “We have folks who were tested, got treated, managed to stabilize and have lived 20, 30, 40 years with the disease. Aging in HIV studies right now is a big open question, because there’s really no way to know what this disease looks like after 20 (or) 30 years. What are the long-term impacts?”

A combination of the blood-brain barrier, along with changes in gut bacteria and additional disease, could be playing a role in the development of neurological symptoms among injection-drug users with HIV. This study will examine all of these possibilities, the researchers said.

“This is a biological, psychological and sociological approach,” Dombrowski said. “It is a really important step in coming to terms with the fact that human beings are very complicated animals.”

The blood-brain barrier forms as a defense against most disease and other agents, including medications, and could be causing problems for HIV patients.

“Viruses tend to cross the blood-brain barrier for one reason or another,” Wood said. “With HIV treatment, many of the drugs being used do not cross the blood-brain barrier, so our brain has been hypothesized as a so-called HIV reservoir. We may never get rid of it. It is there, doing something and causing long-term neurological diseases.”

The research will build on Dombrowski’s rural drug-abuse research in Puerto Rico, following an expanded cohort of HIV-diagnosed patients to examine long-term health and cognitive changes in both drug users and non-drug users. The study participants will also give fecal samples every 12 months, which will allow the research team to investigate any role that gut bacteria may be having on disease evolution.

Wood said this multidisciplinary approach is needed to identify biomarkers, track progression of HIV and understand more fully how the disease manifests in humans over time.

“Why would drug use exponentiate the neurological effects in long-term HIV-infected individuals, even those in treatment, and what are the factors if it does?” Wood said. “Is one the (gut) microbiome? And what are the parameters? The ultimate goal is to find these biomarkers for disease progression.”

These research questions go hand in hand with studying the opioid crisis in the United States.

“We’re out there looking at a big question that we don’t know the answer to, a question likely to affect a large number of people,” Dombrowski said. “The situation in the United States with the opioid crisis right now is that it has yet to have a major HIV component. But there is more injection-drug use going on in the United States right now than ever, and we saw in Scott County, Indiana, what can happen. There were 400 cases in two months in a town of 5,000 people.

“This is a problem that’s on the horizon for the country, and we’re lucky to be able to be in a position to research it before what many of us on the frontlines of the opioid epidemic think is likely to be the next new wave of HIV infection in the United States.”

Additional team members at Nebraska include Bilal Kahn, Happold Professor of sociology; John West, research associate professor in the Center for Virology; Samodha Fernando, associate professor of animal science; and Kathy Chiou, assistant professor of psychology. The team will collaborate with colleagues Anibal Valentin at the University of the Central Caribbean and Juan Carlos Reyes at the University of Puerto Rico.