HIV/AIDS Cure: The Basics
January 22, 2018
What Does the Term "AIDS Cure" Mean?
The term "cure" refers to strategies that eliminate HIV from a person's body, or permanently control the virus and render it unable to cause disease. A "sterilizing" cure would completely eliminate the virus from the body. This "type" of cure is typical to achieve and impossible to measure with current technology. A remission, sometimes referred to as long-term viral suppression off ART or sustained viral remission, would suppress viral load, keeping it below the level of detection without the use of ART. The virus would be undetectable on the most sensitive tests currently available, but traces of the virus may remain in the body and could lead to a reinfection. Just like cancer, a person in remission may be undetectable for many years and then rebound with a strain of virus dormant in their body.
Researchers are still debating and discovering what it means to be cured of HIV. Although some cases of remission have been reported, almost all have now rebounded. It takes time to be certain that HIV can no longer cause disease.
What Types of Cure Strategies Are Being Investigated Today?
There are three broad strategies being explored. Each takes a different approach to the fundamental challenge of HIV infection -- the ability of HIV to hide in cells that are inactive and not dividing. As long as the cells are not dividing, the virus isn't copying itself and is considered "latent". Cells that carry latent virus are, collectively, referred to as viral reservoirs. Most of the viral reservoir is in memory CD4+ T cells (latent immune cells), which are designed to live in the body a long time. A truly effective cure will either have to eliminate these viral reservoirs or ensure that virus that gets activated does not reestablish infection in the body.
"Shock and Kill"
This two-step strategy aims to flush (or shock) the virus out of resting cells with one kind of drug intervention and then follow up with another intervention (likely something from the strategies below) to effectively kill infected cells. Many of the shock agents being considered are currently used as cancer treatments, although researchers are trying to discover new drugs as well. The "kill" component of this one-two punch could involve a therapeutic vaccine, if an effective one can be developed or other interventions to intensify or improve the immune response to HIV.
This strategy has three major initiatives underway, all of which require the genetic alteration of immune cells. The first seeks to change the cells so that HIV can't infect them. The genes are edited to remove a protein receptor known as CCR5- the door HIV uses to enter CD4 T Cells. The second initiative would enable immune cells to find and fight HIV more efficiently. The immune cells are modified to better detect latently infected cells in the body. The third initiative is the most complex and involves removing HIV from the DNA of infected cells.
All gene modification involves extracting immune cells from HIV-positive individuals and then modifying them. The challenges are significant. It's difficult to get white blood cells infected with HIV, and no one yet knows the quantity of modified genes needed to achieve results. Researchers are working on developing a method to deliver gene editing technology directly into the body without removing cells. The hope is that this approach will quickly spread modified genes through the whole body.
Immune modulators refer to any type of drug or procedure that causes some type of sustained change in the immune system to better fight HIV. Successful immune modulation would identify latent cells holding the virus before the cells reactivate and kill HIV once cell division begins again.
Researchers are exploring natural killers of HIV and how to make them more potent through immune modulation. These natural killers include HIV-specific CD8+ T cells, NK cells, broadly neutralizing antibodies. Another immune modulation that could make a difference involves turning off immune cells' "exhaustion markers" that signal a cell to die.
What Are Challenges Related to Cure Research?
Many issues make cure research difficult. First, there is no clear way to measure the HIV reservoir. The two leading approaches measure the number of HIV RNA copies in the blood, or the number of HIV DNA copies in cells. But HIV RNA in the blood does not detect viral copies already integrated into resting cells. Measuring DNA often doesn't provide an accurate picture either, since the cheapest and most available technologies cannot distinguish replication-competent virus from damaged, harmless virus. A more precise measure or assay, called the quantitative viral outgrowth assay, requires the use of large numbers of cells and cannot be done with a simple blood draw.
Unknown risks and benefits associated with all these current strategies represent a second major challenge to cure research. Trial participants must be able to understand these risks and potential benefits. In order to test for a cure, participants must stop treatment to enable researchers to look for a viral rebound of HIV. There are no standardized guidelines for how to time such "treatment interruptions" and minimize risks for cure-related trial participants and their partners. Finally, cure strategies may look different for men, women and children -- biological differences between sexes and differences in adult versus pediatric immune systems mean that it is unlikely there will be a "one-size-fits-all" cure approach.
What Happens Next?
Cure research is expanding, with a range of trials planned or under way. See avac.org/pxrd for a list of these trials.
How Can Advocates Get Involved?
Many of the research strategies being developed require expensive equipment and specific training to administer. To show success or failure additional resources may be needed. These resources are not available in most global settings. Advocates can increase awareness around the need for these technologies in order to prepare for future cure trials in humans.
[Note from TheBody.com: This article was originally published by AVAC in Nov., 2017. We have cross-posted it with their permission.]
This article was provided by AVAC: Global Advocacy for HIV Prevention. Visit AVAC's website to find out more about their activities and publications.
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