New York, March 30 : A team of researchers has discovered an important vulnerability of the AIDS-causing retrovirus HIV, and has shown in preclinical experiments that a widely used diabetes drug, metformin, seems able to exploit this vulnerability.
The findings, published in the journal Nature Immunology, suggests that HIV (human immunodeficiency virus), when it infects immune cells called CD4 T cells, helps fuel its own replication by boosting a key process in the cells’ production of chemical energy.
They also 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 findings suggest that metformin and other drugs that reduce T cell metabolism might be useful as adjunct therapies for treating HIV,” said researcher Haitao Guo University of North Carolina.
About 38 million people around the world are living with HIV infection, according to the World Health Organization’s most recent estimates.
Doctors currently treat these infections with combinations of antiretroviral drugs to suppress HIV replication. However, many patients despite this treatment show signs of residual viral replication and immune impairment.
Even patients who respond well to antiretroviral drugs must take them indefinitely, since HIV inscribes itself into the DNA of some infected cells, and the drugs cannot clear this viral genetic “reservoir.”
Moreover, the toxicity of anti-HIV drugs means that many patients can take them only intermittently. Thus, despite progress, there is still much room for improvement in HIV treatment.
For the study, the team analyzed CD4-cell gene expression data from a study of HIV-infected people and found that the gene-expression patterns most closely related to poor outcomes among these patients involved an energy-production process called oxidative phosphorylation.
They then found that drugs and other chemical compounds that inhibit oxidative phosphorylation in CD4 cells can inhibit HIV’s ability to replicate in these cells.
The team confirmed with further experiments in primary human CD4 cells, and in mice with human CD4 cells, that metformin suppresses HIV replication in these cells.