The research team analyzed CD4 cell gene expression data from a study with HIV-infected people in Africa and Asia.
Researchers at the University of North Carolina Medical School (UNC) discovered that when HIV infects immune cells called CD4 T cells, it promotes its own replication by promoting a key process in the production of chemical energy in the cells. In addition, they found that the diabetes drug metformin inhibits the same process and thereby suppresses HIV replication in these cells in both cell culture and mouse experiments.
“These results suggest that metformin and other drugs that reduce T-cell metabolism could be useful as add-on therapies to the treatment of HIV,” said Dr. in a press release.
Many patients show signs of residual virus replication and immunodeficiency despite this treatment, but even patients who respond well to antiretroviral therapy (ART) must continue to take it indefinitely, as HIV inscribes itself in the DNA of some infected cells and the drugs do so Virus cannot eliminate genetic reservoir. In addition, the toxicity of many anti-HIV drugs means that many patients can only take them intermittently, which, according to the study’s authors, leaves a void in HIV treatment.
The research team analyzed CD4 cell gene expression data from a study with HIV-infected people in Africa and Asia. They found that the gene expression patterns most closely related to poor outcomes in these patients involve an energy production process called oxidative phosphorylation. They found that drugs and other chemical compounds that inhibit oxidative phosphorylation in CD4 cells can inhibit the ability of HIV to replicate in these cells.
Metformin is believed to be safe and well tolerated, and the researchers confirmed with further experiments on primary human CD4 cells and in mice with human CD4 cells that metformin suppresses HIV replication in these cells.
The researchers also looked at a previous study of patients with HIV taking ART that showed after 6 months of treatment that patients with type 2 diabetes had, on average, 33% less HIV in their blood than non-diabetic patients in the cohort. The diabetic patients also had higher baseline CD4 cell levels and faster recovery of these levels with ART.
The team tracked HIV’s ability to increase oxidative phosphorylation in CD4 cells by increasing levels of NLRX1, a protein associated with mitochondria. NLRX1 appears to be a key metabolic switch that HIV uses to improve its replication in CD4 cells, making it a potential target for future HIV treatments, according to the study.
“This work shows the importance of CD4 cell metabolism in HIV and suggests that it can be used with reused drugs like metformin, for example, to target the HIV viral load and restore those disease-fighting CD4 cells,” said the co-senior -Author Jenny Ting, PhD, in a press release.
Researchers plan to continue preclinical studies on metformin’s potential as an anti-HIV treatment or as a therapy that could reduce the need for toxic antiretroviral drugs that could be given to patients earlier to reduce the build-up of HIV reservoirs.
REFERENCE
Diabetes drug may be a new weapon against HIV. UNC School of Medicine. Published March 29, 2021. Accessed March 31, 2021. https://news.unchealthcare.org/2021/03/diabetes-drug-may-be-a-new-weapon-against-hiv/
