Scientists have discovered an important weakness in the human immunodeficiency virus that causes AIDS, and found that a drug used for diabetes appears to be able to exploit this vulnerability.
Scientists from the University of North Carolina School of Medicine, whose study was published in Nature Immunology, concluded that when HIV infects immune cells called CD4 T cells, it helps fuel its reproduction by enhancing a key process in the cells’ production of chemical energy. They also found that the diabetes drug metformin inhibited the same process and thus inhibited HIV replication in these cells, in both preclinical trials in cell culture and mouse experiments.
“These results indicate that metformin and other drugs that reduce T-cell metabolism may be useful as adjunctive therapies to treat HIV,” said first co-author of the study, Dr. Haitao Gu, associate professor in the department of genetics at North Carolina State University in Chapel Hill. Humanity”.
Around 38 million people around the world live with HIV, according to the latest WHO estimates. Doctors are currently treating this infection with a combination of antiretroviral drugs to suppress the reproduction of HIV.
However, many patients despite this treatment show signs of residual virus replication and weakened immunity. Even patients who respond well to antiretroviral drugs should take them indefinitely, because HIV inserts itself into the DNA of some infected cells, and the drugs cannot remove this viral genetic “reservoir”. Moreover, the toxicity of the anti-HIV drugs means that many patients can only take them intermittently. Thus, despite the progress made, there is still much room for improvement in HIV treatment.
A potential new approach to treating HIV is not to attack it directly but to make the cells it infects less suitable for viral replication. For example, other research has shown that HIV boosts CD4 cell energy production, apparently to enhance the virus’s ability to replicate within those cells.
In their study, Gu and colleagues sought to better understand how HIV does this, and whether reversing this metabolic effect could suppress HIV.
In collaboration with Dr. Rafic Pierre Sicily and Dr. Khader Ghoneim at Case Western University, the team analyzed the gene expression data for CD4 cells from a study of people with HIV in Africa and Asia, and found that the gene expression patterns most correlated with poor outcomes among these patients involved On an energy production process called oxidative phosphorylation.
Then they discovered that drugs and other chemical compounds that inhibit oxidative phosphorylation in CD4 cells could suppress the ability of HIV to reproduce in these cells.
One of these drugs is metformin, which is one of the most widely prescribed drugs in the world, safe, well-tolerated, and inexpensive.
Gu and colleagues confirmed that by conducting experiments on primary human CD4 cells, and in mice containing human CD4 cells, metformin inhibits HIV replication in these cells.
The researchers also examined a previous study of HIV patients taking antiviral therapy to discover that after six months of treatment, patients with type 2 diabetes, many of whom were taking metformin, had an average of 33% lower levels. Of HIV in the blood compared to the non-diabetic patients in the group.
Diabetics also, on average, have higher levels of essential CD4 cells and a faster recovery from these levels with ART.
“These realistic results are consistent with the idea that metformin has a significant effect in the fight against HIV,” said Dr. Jenny Ting, a professor in the department of genetics at the University of North Carolina-Chapel Hill.
The team plans to continue preclinical studies of metformin’s potential as an anti-HIV treatment, a treatment that could reduce the need for toxic antiretrovirals and could be given to patients early to reduce HIV reservoir formation.
Source: Medical Express