Brookie Best, ’94, works to help HIV’s most vulnerable victims.
HIV treatments have been remarkably effective over the years in managing the disease, thanks largely to clinical trials. Yet one significant risk group typically falls outside the realm of these trials: pregnant women and their unborn children. Though mother-to-child transmission is now the most common route of HIV infection, the proper dosage of treatments remains widely unknown—too much or too little of the medicine may do both mother and child more harm than good. Brookie Best, Revelle ’94, M.A.S. ’07, devotes her work as a UC San Diego professor of clinical pharmacy and pediatrics to researching where the balance may lie.
Dosages for pregnant women and children are often scaled down from standard doses at a “best-guess” approach. Yet the metabolization of a drug varies widely across bodies, due to factors such as age, weight, hormones and more.
“We find that for nearly every drug, pregnancy alters the way the drug is absorbed and eliminated in the body.”
“We find that for nearly every drug, pregnancy alters the way the drug is absorbed and eliminated in the body,” says Best. “And as these women get further along in their pregnancies, they’re taking the same drug dose as was initially given, so the actual exposure of the drug is dropping lower and lower. When it matters the most—which is right near delivery—they might get the highest risk for the virus to break through or start increasing again, or even become resistant to the drugs because now there’s not enough to keep [the virus] down.”
A decreased drug concentration isn’t the only thing to be worried about—over the duration of a pregnancy, drug exposure can also increase in strength. “If you give too low of a concentration, you put the fetus at risk of acquiring HIV. If concentrations are too high, you could put both mother and baby at risk for toxicity.”
Incorporating pregnant women into clinical research could help find the solution, yet many have excluded these populations due to ethical conundrums and the fear of risk. “There’s no right answer,” says Best, with regards to how to morally include these populations in medicinal studies. Still, she has found ways to work through these concerns, while providing both short- and long-term benefits.
“We conduct our studies on pregnant women with HIV who are already taking a drug because their primary caretaker had no other choice but to give it to her,” Best explains. “We simply ask if we can draw their blood and measure the concentrations. We even give them the results back in real time, so their clinicians can use the information to determine if she wants to increase or decrease the dose. There’s actually a safety incentive for them to enroll in our studies—they couldn’t get this information with their caretakers alone.”
Best’s findings thus far have been incorporated in the Department of Health and Human Services’ treatment guidelines for HIV. Yet she’s committed to finding better answers to these sensitive questions, so that those living with HIV can live well despite their condition. “HIV is a chronic disease—many people live with it for many years,” she says. “The number of women with HIV is in the millions, but they want to have children and families. I want to come up with the safest way for them to do it.”
From Lab to Class
In 2010 and 2013, Best was recognized as the Skaggs School of Pharmacy and Pharmaceutical Sciences Professor of the Year. Best was also a recipient of the 2013/2014 Distinguished Teaching Award for UC San Diego Division Academic Senate members. “I love the interactions with my students,” she says. “They’re always coming up with new questions that I would have never thought of before—it’s a lot of fun for me and it keeps me on my toes.”