HIV and illicit drugs are a bad mix. This scientist found an unexpected reason why

It was as a Ph.D. student that Dionna Williams realized the fundamental flaws in how medical science treats people who have HIV and also use illicit drugs or misuse prescription drugs.

People in this group often have worse outcomes than people with HIV who don’t use these drugs. Drug use and addiction have been linked to faster HIV disease progression, a higher viral load and worse symptoms, including brain-related problems.

For years, many doctors and scientists believed these poor outcomes resulted from people not taking the antiretroviral therapies that keep HIV in check, says Williams, a neuroscientist now at Emory University in Atlanta. No one really tested that hypothesis, though — in part because people who report substance abuse had often been excluded from HIV clinical trials.

The argument didn’t make sense to Williams, who met patients with HIV during a summer program while working on their Ph.D. at Albert Einstein College of Medicine in New York City. “Every person with HIV that has a substance use disorder, they can’t just all not be taking their meds. They can’t all just not be going to the doctor. That’s not possible.” Even people who regularly take their antiretroviral medications have bad outcomes if they also use cocaine, for instance. Perhaps there are biological reasons why HIV, its treatments and illicit drugs are such a bad mix, realized Williams, who uses both she and they pronouns. Their career has been dedicated to exploring those connections.

Earlier this year, for example, Williams and colleagues reported in Fluids and Barriers of the CNS, that in human cells in the lab, cocaine increased one anti-HIV medication’s ability to get past the brain’s protective barrier while decreasing the ability for another. The team found that cocaine can also increase amounts of enzymes that are needed to convert the medications to their active forms.

Such findings suggest the problem isn’t always that people who use illicit drugs aren’t taking their prescriptions, but that they may need higher or lower doses or a different treatment.

Williams’ research embraces those who have been marginalized and excluded partly because Williams understands what it is like to be an outsider.

“I own multiple marginalized identities. In fact, I don’t think I’ve ever met anyone in science that’s like me,” Williams says. “I’m a nonbinary Black woman. I am also queer. I am Autistic. I am [a] first-generation [college student]. I’m from a disadvantaged background.” Williams is also a single parent, martial artist and dancer.

Holding all those identities has helped Williams understand people of all types and to be a better scientist and mentor, they say.

“She is just an amazing young scholar,” says Habibeh Khoshbouei, a neuroscientist at the University of Florida College of Medicine in Gainesville, noting that Williams’ research fields — pharmacology, neuroscience and immunology — are diverse.

Perhaps most impressive is that Williams uses human cells and samples from people, Khoshbouei says. Most researchers, including herself, use lab animals such as rats or mice to study the brain and immune system. Lab animals have carefully controlled diets and living conditions. They are genetically similar. All that makes it easier to interpret results of experiments. Working with people and their cells requires dealing with all the ways humans differ, and often requires hundreds of participants. But it’s the human differences that Williams wants to understand.

“The scale of complexity and dedication and open-mindedness to work with actual human samples, it’s beyond measure. It is not comparable,” to working with animals, Khoshbouei says.

By working directly with human cells, Williams also skips the need to translate findings from animals. That means the findings may be more likely to hold up.

A recent study — on how drugs affect the body more generally — helps illustrate why results in humans don’t always match findings from animal studies. Williams and colleagues probed the bodies of rats, mice and rhesus macaques for activity of 14 genes that make proteins that detect cannabinoids, the active ingredients in marijuana. Rodents and monkeys are often used as stand-ins for humans in medical studies, including studies looking at the possible health benefits of medical marijuana.

For animal studies to be useful, the results should be comparable across species. But when the team looked at the rodents and monkeys to see where the chemical-sensing proteins — called endocannabinoid receptors — are located in the animals, the patterns didn’t match.

Mice made detectable levels of one of the main endocannabinoid receptors in their colons, kidneys, spleen and visceral fat, the team reported February 26 in Physiological Reports. Rats produced it mainly in their kidneys and colons, while macaques made it in their spleens and visceral fat. There was even variation between individuals within a species. “Nothing is the same,” Williams says. “If we don’t understand this, we’re not going to be able to make good therapies.”

Similarly, some people may make far more or less of drug-sensing proteins in certain organs, Williams says. Many scientists would dismiss the variation as noise. “That’s not noise,” Williams says. “It’s really important information about people’s biology.”

Williams is “fearless,” says Gonzalo Torres, a neuropharmacologist at Loyola University Chicago’s Stritch School of Medicine. “She’s not afraid to go into research areas [in which] she’s not necessarily an expert.” Torres directs mentorship programs including the MINDS program for diverse junior faculty in neurosciences, in which Williams participated.

Williams stands out for being smart, strategic, creative, persistent and tenacious, Torres says. “She’s hungry, she wants to know, she wants to pursue.” And Williams works hard to develop the skills and knowledge needed to answer their research questions. “Every time she’s going deeper, and by going deeper, she grows, and her research team grows. She’s becoming a superstar,” Torres says.

Williams credits their autism with helping “to connect topics in a very interdisciplinary way.” Autism allows them to see beyond societal standards and structures, they say. “We think differently. We see the world differently.… When people say ‘This can’t be done,’ [I say], ‘Well, why not?’ Or ‘No one’s looking at that,’ ‘Why aren’t they?’”