Scientists Are Pursuing Multiple Approaches to an HIV Cure, Expert Says
The HIV research community continues to make progress toward finding a cure, but is still grappling with a range of challenges, an expert in the field said in a webinar on June 6. The event was the first in a series of educational webinars taking place this month entitled "CUREiculum," which are organized by AVAC -- Global Advocacy for HIV Prevention.
Nicolas Chomont, Ph.D., from the University of Montreal, led the webinar. He explained the search for an HIV cure, the difficulties such research faces and the various strategies for a "functional" cure of HIV that are being pursued.
There are two basic definitions for curing HIV, Chomont explained. One is the eradication of all HIV from the body. The other is a "functional cure" in which the person is not on antiretroviral therapy, but has no symptoms, does not risk transmitting the virus to others and continues to have an undetectable viral load. The latter definition is a more likely scenario for research at this time, he said.
The basic problem in curing HIV is the fact that the virus creates a "latent reservoir" of inactive memory cells that may be reactivated once someone stops taking antiretroviral medication, Chomont said. The size of that reservoir varies from person to person, but is smaller the earlier HIV treatment is started. One of the challenges in cure research is determining that size: At this point, there is no standard test for this, Chomont noted.
Chomont described two strategies that are currently being pursued for targeting inactive, HIV-infected cells in order to prevent their reactivation. The "kick and kill" approach (also referred to as "shock and kill") activates the cells in the latent reservoir with the help of latency reversing agents, such as histone deacetylase inhibitors. It then uses medications to kill those cells, thereby also destroying the virus.
By contrast, the "immune modulation" approach strengthens the body's own immune system to help it kill the infected cells. This will likely require a combination of several immune modulators or an immune modulator plus other therapies, Chomont said.
One type of immune modulator being explored is a therapeutic vaccine. While therapeutic HIV vaccines were not effective in past studies, current research informed by new knowledge seems more promising, Chomont said. One approach is to use a class of drugs called broadly neutralizing antibodies to target many different mutations of the virus. Another is gene modification, which changes either the DNA of HIV itself or a component of the infected person's cell DNA that the virus needs in order to survive, such as CCR5 receptors on CD4 cells. Molecular scissors -- also known as zinc fingers -- are being tested for this manipulation of the genome. The novel CRISPR (clustered regularly interspaced short palindromic repeats) technology is also being investigated for this purpose.
A successful HIV cure must be safe, effective, durable, affordable and accessible, Chomont concluded. Even if one is developed, however, it will not be appropriate for everyone living with HIV, he cautioned. Treatment with antiretrovirals will therefore continue to be an important component of the fight against HIV.