A Novel “Kick and Kill” Strategy to Eliminate HIV

These updates often focus on HIV cure strategies based on methods to eliminate latent reservoirs of HIV infection, the main barrier to a cure. amfAR-funded scientist Dan Barouch of Harvard University, with colleagues from the Ragon Institute, Gilead Sciences, and the University of Massachusetts, now present the results of a study using a novel combination of an immune activator and an HIV neutralizing antibody. The pairing delayed and, in some animals may have eliminated, viral rebound in their monkey model.

 Dr. Dan Barouch

Dr. Dan Barouch

Writing in the October issue of the prestigious journal Nature, Barouch and associates report on 44 monkeys infected with a strain of HIV. This hybrid strain, known as SHIV, contained components of both human and simian immune deficiency viruses.

Beginning on day 7 after infection, all animals received daily antiretroviral therapy (ART) for 96 weeks. They were then divided into four groups: one received nothing; one an antibody (PGT121) capable of neutralizing HIV; one an immune stimulant, vesatolimod (also known as GS-9620), which activates CD4+ T cells and other immune cells including monocytes and natural killer (NK) cells, via a protein known as TLR7; and a final group received both the antibody and the immune stimulant.

ART was continued for another 34 weeks, then stopped. The hope was that vesatolimod would “kick,” or activate, latently infected T cells, rendering them more susceptible to binding by the antibody, and also stimulate monocytes and NK cells to help “kill” infected T cells.

The results were striking.

In all the treated monkeys, the combination of stimulant and antibody delayed time to reappearance of virus after ART was stopped. In those monkeys showing no viral rebound, intensive investigations found no evidence of virus for more than 6 months of follow up.

Given that viral rebound can occur in humans long after stopping ART, the authors cautioned that they “cannot exclude the possibility that exceedingly low levels of virus may still exist in these monkeys.” In addition, ART was begun rapidly—only one week after infection—which is unlikely in the real world of HIV infection. But despite these caveats, the investigators concluded that their experiments provide proof of concept for combining neutralizing antibodies with immune activators in the design of a potential HIV cure.

Dr. Laurence is amfAR’s senior scientific consultant.