Concepts of HIV Cure Explained

Segment Description: Ian Frank, MD, Professor of Medicine at the Perelman School of Medicine, explains the different conceptual understandings of what an HIV cure might entail.

Interview Transcript (modified slightly for readability):

Frank: There are a couple of different concepts for HIV cure. A traditional curative strategy means eliminating all sources of HIV, all remnants of HIV, getting rid of the latent reservoir of about a million latently infected cells in somebody with virologic suppression on antiretroviral therapy. That kind of curative strategy has focused on bone marrow transplantation, we now have 2 and maybe a third individual who has been cured of their HIV infection. All of these individuals have had a bone marrow transplant with a donor who was CCR5 negative, individuals who have this delta 32 homozygote genotype lack CCR5, the coreceptor that HIV needs in order to enter cells.

And when they received a transplant, following extensive chemotherapy to wipe out their own cells, which was needed because of their leukemia or lymphoma, individuals given bone marrow with this particular mutation failed to allow any virus to replicate. So these are the few individuals that have had a real cure.

In general, when we're talking about curing HIV, we're talking about establishing a functional cure, giving gene therapy to immunized cells so that those cells can't become infected. We've given individuals zinc finger nucleases. In other words, giving them a treatment that cleaves the gene that encodes the CCR5 receptor, making those cells uninfected.

Another strategy is to use latency reversing agents, agents which stimulate virus out of the latent reservoir. And in the setting of continued antiretroviral therapy, trying to reduce the size of the latent reservoir by shocking the virus out of these cells, and then killing it with the antiretroviral therapy.

The other strategy we're using is to use either monoclonal antibodies, broadly neutralizing monoclonal antibodies, or some other immunologic strategy like a therapeutic vaccine, in order to try to improve upon the immune response that individuals get and in that way hopefully prevent virus from rebounding after antiretroviral therapy is stopped. Another strategy I should mention because I'm an investigator in this kind of strategy is to use interferon to boost the natural killer cell response and again, improve upon the immunologic potential to control virus replication in the absence of antiretroviral therapy