Commonly Prescribed Diabetes Drug May Be Useful in Fight Against HIV

April 1, 2021
Jaime Rosenberg

If replicated in future studies, the findings have important implications for the millions of people living with HIV, many of which display signs of residual viral replication despite treatment.

Preclinical research is putting a common, inexpensive drug used to treat diabetes in the mix for potential ways to fight HIV.

The findings, recently published in Nature Immunology, show that metformin subdues HIV’s ability to replicate in CD4+ T cells, the immune cells that the virus infects. When HIV infects these immune cells, it boosts a key process in the cells’ production of chemical energy, resulting in viral replication. Metformin, it seems, is able to hinder this process called oxidative phosphorylation.

“These findings suggest that metformin and other drugs that reduce T cell metabolism might be useful as adjunct therapies for treating HIV,” said the study’s co-first author Haitao Guo, Ph.D., assistant professor in the University of North Carolina (UNC) Department of Genetics at the UNC School of Medicine, in a press release announcing the results.

If replicated in future studies, the findings have important implications for the millions of people living with HIV, many of which display signs of residual viral replication despite treatment.

This study is the latest in a newer wave of research looking at the possibilities of making it harder for these infected cells to virally replicate, which contrasts the typical treatment approach of treating HIV.

The group of researchers of the current study analyzed CD4-cell gene expression data collected from people living with HIV in Africa and Asia. They observed that the gene-expression patterns most closely linked to poor outcomes was related to oxidative phosphorylation.

From there, the researchers discovered that treatments that suppress this process in CD4 cells can subsequently prevent HIV’s ability to replicate.

“This work shows the importance of CD4 cell metabolism in HIV, and suggests that it may be targetable, for example with repurposed drugs such as metformin, to reduce HIV viral load and restore these disease-fighting CD4 cells,” said Jenny Ting, Ph.D., assistant editor in the UNC Department of Genetics at the UNC School of Medicine, in a statement.

The publication also includes the researchers’ findings from an analysis of a previous study of patients living with HIV taking antiretroviral therapy (ART)—the cornerstone of HIV treatment. In patients who also had type 2 diabetes, likely meaning they also take drugs like metformin, HIV levels in the blood were approximately 33% lower compared with patients without diabetes after 6 months.

Notably, these patients with diabetes had higher baseline CD4 cell levels and swifter recoveries of these levels with ART.