Despite being preventable and curable, tuberculosis remains the world’s leading infectious disease killer. According to the World Health Organization, an estimated 10.6 million people became ill with tuberculosis and 1.3 million died from the disease in 2022 alone.

Researchers across the UCSF School of Pharmacy are working to change that reality, collaborating with scientists worldwide to develop faster treatments, design smarter drug regimens, and build global partnerships to control the disease.

Their work spans the entire tuberculosis research pipeline — from computational drug development to clinical trials and real-world implementation — with the goal of making treatments shorter, safer, and easier to complete.

Shorter treatments, better outcomes

Tuberculosis treatment has long required patients to take multiple drugs daily for six months or longer, and even longer for drug-resistant infections. The complexity and side effects of these regimens made treatment difficult to complete, contributing to the rise of drug-resistant strains.

Research led in part by UCSF scientists has helped change that trajectory. A landmark clinical trial demonstrated that drug-susceptible tuberculosis could be treated in four months instead of the traditional six, an advance built on pharmacology research by Rada Savic, PhD, a professor in the Department of Bioengineering and Therapeutic Sciences and co-director of the UCSF Center for Tuberculosis.

Savic’s research uses computational methods to understand how tuberculosis drugs behave in the body and how combinations of medications can be optimized to improve treatment.

“The biggest advance is finding ways to integrate different models,” Savic said. “We have AI tools, statistical models, systems pharmacology models, and classical  [pharmacokinetic pharmacodynamic (PKPD)] models. The real innovation is understanding how to combine these models to answer the scientific question and identify promising drug combinations faster.”

Building global partnerships for drug development

Because tuberculosis disproportionately affects communities with limited resources, solving the disease requires collaboration across countries, research institutions, and health systems.

Savic is helping lead one of the largest efforts to coordinate this work. In 2024, she received a $30.8 million grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health to establish a new international research collaboration focused on developing improved tuberculosis treatment regimens.

The five-year award supports the Preclinical Design and Clinical Translation of TB Regimens (PReDicTR) Consortium, a multidisciplinary network of scientists, drug developers, and clinical researchers working to identify the most promising drug combinations for future clinical testing. Savic serves as a principal investigator alongside collaborators from institutions including Johns Hopkins University, Vanderbilt University, and Weill Cornell Medicine.

“In the consortium we have all industry partners,” Savic said. “That means we can work with new assets and new drugs.” These collaborations allow researchers to analyze large datasets from multiple sources and move promising therapies toward clinical trials more efficiently.  

“Our strength is that we have access to a lot of data, but building partnerships really comes down to trust and making sure the output feeds progress, innovation, and science,” Savic said. “High integrity and responsibility is the nature of UCSF and the School of Pharmacy. The key is doing top-notch science that is relevant and targeted and accelerates the field.”

Through initiatives like PReDicTR, researchers integrate data from laboratory experiments, animal models, and human studies to determine optimal drug doses and treatment schedules.

Global cooperation is essential not only for scientific discovery but also for ensuring treatments work in real-world settings.

“Most patients are in the global south,” Savic said. “You cannot come up with solutions here and expect them to be accepted elsewhere.”

Even when a treatment proves effective in clinical trials, factors such as cost, health care infrastructure, and medication storage requirements can determine whether it can be successfully implemented.

Designing treatments that work in real-world settings

Tuberculosis is also deeply connected to social and economic conditions. The illness spreads most easily in crowded environments and disproportionately affects communities with limited access to health care, stable housing, and access to treatment.  

Clinical trials around the world must be highly adaptable to these various environments, and to the availability of resources. That challenge is one reason pharmacists play a critical role in global tuberculosis care, according to Katherine Yang, PharmD, MPH, professor in the Department of Clinical Pharmacy at the UCSF School of Pharmacy.

“It’s really a disease of disparity,” said Yang, who helps ensure investigational drugs can be safely managed across a wide range of health systems. “Treatment of tuberculosis requires a lot drugs, taken for a very long time, and people often can’t work during treatment.” 

Monitoring drug safety worldwide

Ensuring that medications remain safe and effective for a global population is critical.

“Pharmacovigilance is basically safety monitoring,” Yang said. “Every clinical trial has to look at every adverse effect someone gets in the study and decide what to do about it.”

Because tuberculosis treatment often involves multiple medications taken for months, pharmacists play a key role in identifying safety signals and adjusting treatment strategies.

“And who better to monitor drug safety than the pharmacist?” Yang said.  

A global challenge — and a solvable one

Despite the complexity of tuberculosis and the challenges of drug resistance and global health inequities, researchers believe the tools to control tuberculosis are finally within reach.

“It’s a big shame on our humanity that people are still dying from TB,” Savic said. “The most important thing is communication and aligning people around a shared mission.”