NIH-Funded Scientists Create Potential Long-Acting HIV Therapeutic

Scientists have created a new molecule that shows promise for controlling HIV without daily antiretroviral drugs. The molecule foils a wider range of HIV strains in the laboratory than any known broadly neutralizing HIV antibody and is more powerful than some of the most potent of these antibodies. In addition, the molecule safely protected monkeys from infection with an HIV-like virus during a 40-week study period. Together, the data suggest that the molecule could, with further research, be used to subdue HIV in humans. The authors note that the molecule potentially could be used as both a preventative drug and as a treatment. The new findings appear in the 18 February issue of the journal Nature.

“This innovative research holds promise for moving us toward two important goals: achieving long-term protection from HIV infection, and putting HIV into sustained remission in chronically infected people,” said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The research was led by Michael Farzan, a professor in the department of infectious diseases at The Scripps Research Institute in Jupiter, Florida. The work was funded primarily by NIAID.

The new molecule is called eCD4-Ig and works by tightly binding to two unchanging sites on the surface of HIV that the virus uses to attach to receptors on cells called CD4 and CCR5. Typically, when HIV attaches to these receptors, it unlocks a door to the cell and gets inside. However, when eCD4-Ig binds to HIV, it effectively takes away the virus’s key, locking it out of the cell and preventing it from multiplying.

“Our molecule appears to be the most potent and broadest inhibitor of HIV entry so far described in a preclinical study,” said Dr Farzan. “If one could inject either eCD4-Ig or our gene therapy tool into people with HIV infection, it might control HIV for extended periods in the absence of antiretroviral drugs. Further research will help illuminate the promise of these approaches.”

To build on their findings, the scientists are studying both the therapeutic potential of eCD4-Ig in monkeys infected with HIV-like viruses and the ability of eCD4-Ig to prevent infection against a wider range of HIV and HIV-like strains.

NIAID has funded the newly published and ongoing research through an initiative called Beyond HAART: Innovative Therapies to Control HIV-1, which supports the development of strategies for suppressing HIV in the absence of antiretroviral drugs.