This article originally appeared in the Breakthroughs newsletter.
Growing threats of antimicrobial resistance. Emerging diseases like dengue and Zika. Complications of aging with HIV/AIDS — and the continued quest to develop a cure.
These are just a few of the significant, global challenges that investigators are confronting through collaborative, cutting-edge basic and clinical research within the Division of Infectious Diseases in Feinberg’s Department of Medicine.
While committed to discovering underlying mechanisms behind a wide range of infectious diseases, scientists in the division also keep an eye toward the clinic; their aim is to ultimately translate novel findings into new approaches for prevention, diagnosis and treatment around the globe.
“We see so much discovery that comes from bench research, but that research has to be translatable,” said Babafemi Taiwo, MBBS, ’06 GME, chief of Infectious Diseases. “To do that, we encourage strong collaboration between laboratory scientists and clinical scientists to really get at the questions that are most important in the field.”
Scientists Focus on a New Paradigm in HIV Care
Although the last few decades have been marked by major advancements in prevention and therapy, human immunodeficiency virus (HIV) remains a significant health challenge worldwide.
There is no cure for HIV, and antiretroviral therapy (ART) — medications that suppress the virus — must be used by a patient every day, for life. Patients with HIV are now living longer than ever, and new questions of how to manage HIV alongside aging are also arising for the first time.
Feinberg scientists are leading investigations to address each of these areas. In particular, improving therapeutics for people living with HIV — by reducing the frequency or length of administration of ART — is a primary focus. Taiwo and collaborators published some of the first studies in this area. Now, Northwestern is participating in several phase III clinical trials evaluating the efficacy of a reduction in HIV treatment.
“If somebody is taking three drugs, whereas they needed only two, we want to avoid whatever cost that third brings, whether it’s financial or toxicity,” said Taiwo, also the Gene Stollerman Professor of Medicine. “This could be a game-changing shift in how HIV is treated globally.”
The clinical team is also working closely with laboratory scientists. “We’re going back to the lab to ensure that the promising results we’re seeing in clinical practice are not translating to potential harm on the cellular level,” Taiwo said. “It’s a fine collaboration between clinical investigators and bench scientists.”
Through discoveries that offer critical new insights into the biology of the virus and its susceptibilities, scientists in the division are also contributing to the ultimate goal: finding a cure for HIV.
Eun-Young Kim, PhD, ’02 GME, research associate professor of Medicine in Infectious Diseases, is dedicated to identifying host gene variations that influence susceptibility to infections like HIV.
“A differential advantage in responding to HIV is associated with variances in the genes relevant to the virus life cycle and immunity,” Kim said. “Our studies focus on the host defense pathways that promote natural resistance to the viral infection. This may prove practical for identifying strategies to achieve a cure for HIV.”
In 2016, Northwestern Medicine scientists published findings in Nature that demonstrated HIV is still replicating in lymphoid tissue, even when it’s undetectable in the blood of patients on ART — providing critical insights into how HIV persists in the body.
The study, led by Steven Wolinsky, MD ’82 GME, the Samuel Jefferson Sackett Professor of Infectious Diseases, and co-authored by Kim, may help chart a path to a cure.
“Finding a cure for HIV is possible,” Taiwo said. “There aren’t any clear answers right now, but we’re looking at some very exciting leads.”
New Frontiers in HIV Co-morbidities
As the HIV-infected population has aged, certain conditions are now known to be more common in people with long-standing HIV infection — including cardiovascular disease, some cancers, neurocognitive disorders, and liver infections like hepatitis B and C.
“Despite all the progress that has been made in HIV, we know that people with HIV are still dying earlier than people who are HIV-negative,” Taiwo said. “Trying to understand how to manage the aging HIV population — and ultimately, to equalize life expectancy — is a focus of a lot of our work.”
As such, the division has formed collaborations with investigators in other disciplines to address such co-morbidities — including Matthew Feinstein, ’11 MD, ’17 MS, ’13 ’17 GME, assistant professor of Medicine in Cardiology, who researches cardiovascular complications of HIV infection, as well as scientists in The Ken & Ruth Davee Department of Neurology, the Division of Hepatology and the Robert H. Lurie Comprehensive Cancer Center.
Claudia Hawkins, MD, ’06 GME, associate professor of Medicine in Infectious Diseases, investigates the relationship between HIV and viral hepatitis B and C, especially through epidemiologic studies in Tanzania and Nigeria. She published some of the first data on the prevalence of hepatitis B and C co-infection in HIV-infected populations in these countries, as well as the effect of viral co-infection on liver disease progression and death.
“We now have a much better picture of the true impact of the hepatitis B virus (HBV) globally in HIV-infected populations and how viral hepatitis B co-infection impacts HIV,” said Hawkins, who is also involved in developing clinical trials for potentially curative agents for hepatitis B. “Because of our work overseas in HBV endemic areas, it’s also improved our understanding of HBV locally, where the burden of infection is typically much lower.”
In fact, a global health reach is central to the Division of Infectious Diseases. Over half of the research out of the Center for Global Health overlaps with the division, Taiwo notes, and there is also an extensive partnership with Northwestern’s Department of Biomedical Engineering to address the global need for rapid diagnostics for the range of infectious diseases.
Uncovering the Genetics of Antimicrobial Resistance
Antimicrobial resistance — the ability of bacteria and other microbes to persist despite medications — has been recognized by The World Health Organization as a global threat.
“The word ‘global’ is used, but it’s also a present threat, even in Chicago,” Taiwo said. “This is going to shape the next decade, and we want to be well-prepared as a division to lead in solving that problem.”
In order to address this public health threat, scientists throughout the division are probing the pathogenesis of resistance, with an emphasis on the genetic mechanisms responsible for virulence.
Within his lab at Feinberg, Egon Ozer, MD, PhD, ’08 ’12, GME, assistant professor of Medicine in Infectious Diseases, studies the genomics of bacteria, in particular a common strain named Pseudomonas, which is often associated with hospital exposure and shows increasing resistance to antibiotics.
Through novel bioinformatic techniques, Ozer uses comparative genomics to identify why some strains might become more infectious or lead to worse outcomes.
“We want to get down to the genetic level and determine what makes pathogens different, which could be used to develop new diagnostics that identify infections more quickly and accurately, or might be targets for therapeutics in the future,” Ozer said. “We want to be able to move the personalized medicine movement into pathogens.”
The Future of Research
Given their public health prominence, investigations into HIV treatment and antimicrobial resistance will remain central focuses in coming years.
But Taiwo notes that the division is also forging into other research areas as well, including emerging diseases like dengue and Zika. Research into infections that surround transplantation — due to the immune suppression patients must undergo — is also an emerging strength of the Division, Taiwo said, noting the asset of Northwestern’s Comprehensive Transplant Center.
“Along with HIV and antimicrobial resistance, we want to evolve into a world-class program for transplant infectious disease research,” Taiwo said. “We have a real opportunity to lead in helping to better understand the risk factors associated with these infections, as well as identifying optimal ways to treat them.”