Can FDA-Approved MS Drug Block HIV Infection?

An FDA-approved immunosuppressive drug used to treat multiple sclerosis may be able to block HIV infection and reduce the latent reservoir of virus, according to investigators from George Washington University.

Results on the potential use of fingolimod were published in PLOS Pathogens.

The antiretroviral (ART) drugs which target HIV have helped the world make immense progress in curbing the epidemic.

But side effects, varying efficacy, and drug resistance issues have made it advantageous to also pursue the development of alternative therapeutics.

In the PLOS Pathogens study, investigators sought to discover if fingolimod could inhibit HIV-1 infection and generation of latent reservoir in CD4 T cells.

In testing, fingolimod blocked cell-free and cell-to-cell transmission of HIV, reducing latent virus.

“These results indicate that Fingolimod merits further investigation as an exciting novel therapy for HIV,” authors wrote.

The drug reduces the surface density of CD4 T cells, inhibiting the ability of the virus to bind to human cells. It also decreases phosphorylation of SAMHD1, which is associated with reduced levels of HIV infection.

Fingolimod, also known as FTY720, is an immunomodulatory compound that acts as a Sphingosine-1-phosphate receptor (S1PR) non-selective agonist and a selective antagonist of S1PR1.

FTY720 was first synthesized using the natural fungal compound myriocin and is clinically approved for treatment of Multiple Sclerosis. In that context, the drug is well-tolerated taken orally on a daily basis.

FTY720 has activity at 4 of the 5 S1P receptors and has been shown to cause downregulation of S1PR1 in lymphocytes and act as a modulator of S1P signaling, effecting changes in chemotaxis, proliferation, and cell cycle state of lymphocytes and other cells. In the case of S1PR1, FTY720 binds to this receptor when phosphorylated and causes its internalization and loss of signaling.

Overall, the investigators suggest that targeting the Sphingosine-1-phosphate pathway with FTY720 may be a novel strategy to inhibit HIV replication and reduce the seeding of the latent reservoir.

"While antiretroviral drugs have been effective in treating HIV thus far, drug resistance, negative side effects of antiretroviral therapy, and its varying efficacy underscore the need to develop alternative treatment and prevention options," said Alberto Bosque, PhD, MBA, assistant professor of microbiology, immunology, and tropical medicine at the GW School of Medicine and Health Sciences. "For the first time, our research team found that by targeting the receptors to the signaling molecule Sphingosine-1-phosphate (S1P), we could effectively block HIV infection and cell-to-cell transmission of the virus and consequently reduce the seeding of the latent virus in the test tube."