HIV Drugs Show Promise in Preventing Life-Threatening Abscesses

Bacterial infections can give rise to abscesses, which are pockets of deceased cells and debris encircled by inflammatory immune cells. These abscesses contribute to the multiplication of bacteria, leading to heightened inflammation and additional harm to nearby tissues.

In severe cases, these immune responses can spread throughout the body, resulting in life-threatening organ failure known as sepsis. Despite the severity of these outcomes, the formation of abscesses and effective preventive measures were not well understood until recent research shed light on a key mechanism. 

Researchers from Brigham and Women’s Hospital conducted investigations using preclinical models to identify a critical process driving the formation of liver abscesses. Their findings, published in the journal Proceedings of the National Academy of Sciences, highlight the role of reverse transcription, a process where DNA is synthesized from RNA. 

The study involved the use of RNA-sequencing to analyze liver gene transcripts from mice infected with Escherichia coli. The researchers observed that abscess formation correlated with increased expression from endogenous retroviruses (ERVs), which are remnants of viruses that integrated into the mouse genome following previous infections. 

The researchers hypothesized that DNA produced by ERVs could trigger inflammatory immune responses, causing damage to surrounding cells and ultimately leading to abscess development. If this hypothesis held true, inhibiting the activity of ERVs might prevent abscess formation. 

To test this idea, the team treated mice with a combination of reverse transcriptase inhibitors—antiretroviral drugs commonly used to manage HIV infections. These drugs were employed to block the expression of ERV DNA. The results were promising: a single dose of the inhibitor cocktail administered promptly after bacterial infection was sufficient to prevent abscess formation. 

Corresponding author Matthew Waldor, MD, Ph.D., from the Division of Infectious Diseases, commented on the findings, stating, “Our findings suggest that drugs used to treat HIV can be used to prevent inflammatory complications of bacterial sepsis.” This implies a potential repurposing of existing antiretroviral drugs for the prevention of severe complications associated with bacterial infections. 

It’s noteworthy that the susceptibility to abscesses varied among mice based on sex and tissues. This variability prompts further research to understand how antiretroviral drugs can effectively prevent complications like bacterial sepsis in different individuals. Nevertheless, the study offers promise and introduces a novel perspective on the treatment and prevention of adverse consequences following bloodstream infections. 

First author Karthik Hullahalli, a Harvard graduate student in the Waldor lab at the Brigham, emphasized the need for additional investigation, saying, “In mice, abscess susceptibility varies by sex and between tissues, so further work is needed to understand how antiretroviral drugs can prevent complications like bacterial sepsis in different individuals.” Despite the need for further research, the study presents a hopeful outlook and suggests a new approach to mitigating the detrimental effects of bacterial infections through the repurposing of existing HIV management drugs. 

Journal Reference  

Karthik Hullahalli et al, Reverse transcriptase inhibitors prevent liver abscess formation during Escherichia coli bloodstream infection, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2319162121.