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Dissertations build on multiple disciplinary perspectives with new contributions to global health knowledge and practice. Lauren Zalla’s project, guided by infectious disease professors Ada Adimora, MD, MPH, and Joe Eron, MD, is a good example. Bringing clinical expertise to Zalla’s dissertation committee, they helped her design a study that explored racial disparities in the prescription of integrase inhibitors (INSTIs), the newest class of drugs used as antiretroviral therapy (ART) to treat HIV. A paper about the study was recently published in JAMA.

“I was motivated to do this particular analysis because I knew there were racial disparities in the prescription of combination ART when it first became available in the 1990s, but nobody seemed to be asking whether there are still disparities in the prescription of newer and more effective forms of ART,” said Zalla, a PhD student in epidemiology, who recently graduated.

Lauren Zalla presented her research at the recent Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington, photographed here with Dr. Ada Adimora.

Treatment with INSTI-containing ART has been associated with more rapid viral suppression, fewer adverse effects, and a decreased risk of virologic failure and resistance selection, compared with treatment using non–INSTI-containing ART. INSTIs block the action of integrase, an enzyme that facilitates viral replication, and they are currently the preferred form of ART for the initial treatment of HIV, approved by the U.S. Food and Drug Administration on October 12, 2007.

Using data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), the study looked at antiretroviral therapy prescription among Black, Hispanic, and White people starting HIV treatment from 2007 to 2019, and uncovered substantial racial and ethnic disparities in the prescription of INSTIs. From 2007-2014, INSTIs were prescribed to 22% of White patients starting antiretroviral therapy, and to only 17% of Black patients and 17% of Hispanic patients. These disparities persisted for years after INSTIs were approved by the FDA, and after the publication of studies indicating that INSTIs were at least as effective as other treatments for HIV, with fewer side effects.

Zalla says the clinical expertise of Dr. Adimora and Dr. Eron was key to ensuring studies would be useful to clinicians and people living with HIV.

The study also looked at differences in prescribing disparities over time in relation to changes in national treatment guidelines. A national panel organized by the US Department of Health and Human Services frequently reviews the current evidence on HIV treatments and publishes specific recommendations on what treatments should be prescribed. The study found that disparities in the prescription of integrase inhibitors disappeared only after they became guideline-recommended therapy.

“While our study can’t establish causation, it does suggest that guidelines may play a role in ensuring more equitable access to new therapies. Next, I’d like to explore how the guidelines may have played a role – for example, do they influence the prescribing preferences of individual clinicians? Or are insurers more likely to cover new medications once they become guideline-recommended therapy?

“It is an encouraging finding that Black and Hispanic patients are now just as likely as White patients to be prescribed INSTIs. But it took years for Black and Hispanic patients to reach the same level of INSTI prescription as White patients, which is an important finding because it may help explain disparities in viral suppression and other care outcomes among Black and Hispanic vs. White patients who started treatment in recent years.”

Zalla says understanding the relationship between guidelines and prescribing disparities could have important implications for health equity more broadly, beyond HIV.

“We know that treatment advances often exacerbate health disparities (this is known as the ‘inverse equity hypothesis’). Our study suggests that standardized national treatment guidelines might be a useful tool to prevent that from happening.”

Another part of Zalla’s dissertation looked at racial disparities in mortality among people with HIV. A follow-up paper looks at how much racial disparities in mortality could be reduced by eliminating racial differences in clinical care. For example, this could include making sure that everyone receives treatment as soon as they are linked to care, and receives follow-up appointments at guideline-recommended intervals. Zalla says the question is whether eliminating racial differences in clinical care is enough to eliminate racial disparities in care outcomes.

“What we are finding is that eliminating differences in clinical care helps, but it’s not enough. If we want to eliminate these disparities that have been accumulating for decades, we need to spend more resources in groups that have historically been disadvantaged.

“The clinical expertise of Dr. Adimora and Dr. Eron was key to the design of both studies. They helped me understand why integrase inhibitors are important and what barriers prevent some patients from accessing them. Their expertise was necessary to ensure that these studies are ultimately useful to clinicians and people living with HIV.”

Other co-authors on the paper include the other members of Zalla’s dissertation committee – Jess Edwards, PhD (advisor/chair), Stephen Cole, PhD, and Anissa Vines , MD, PhD – along with collaborators from NA-ACCORD.

 Zalla graduated from UNC in August, and is now a postdoc in the Department of Epidemiology at Johns Hopkins.