This fact sheet provides basic information on HIV cure research. For more basic fact sheets visit www.avac.org/intro. Visit www.avac.org/cureiculum to access a suite of educational material on HIV cure topics.
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. Two types of cure are being researched. A “sterilizing” cure would completely eliminate the virus from the body. A “functional” cure would suppress HIV’s viral load, keeping it below the level of detection without antiretroviral treatment (ART). In a functional cure, the virus would be undetectable but traces may remain in the body and could lead to a reinfection. Functional cures are also referred to as “remission”, a term borrowed from the cancer field, because a person living with HIV 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 functional cures have been reported, 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 four 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, also called resting cells. 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 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 is a two-step strategy that aims to flush (or shock) the virus out of resting cells with one kind of drug and then follow up with another drug to kill infected active 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 that intensify 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 of the immune cell are edited to remove a protein receptor known as CCR5—the door HIV uses to enter CD4 T cells. A 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 extract 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. The hope is that this approach will quickly spread modified genes through the whole body.
Stem cell transplants
Hematopoietic stem cells are produced in bone marrow and produce all the blood cells in the body. Stem cell transplants carry a high risk for side effects and are used to treat life threatening illnesses such as cancer. Stem cell transplants are preceded by a process called conditioning. Conditioning eliminates an individual’s immune system to make room for the donor system and decreases the likelihood of transplant rejection. In HIV-positive individuals, conditioning eliminates many, if not all, HIV-infected cells.
In the notable case of Timothy Brown, who was cured of HIV, he received a stem cell transplant for cancer treatment. His transplanted stem cells had no CCR5 receptor, the door for HIV. Stem cell transplants are a last resort for people with both cancer and HIV. This strategy is not currently scalable.
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 integrated in the cells. HIV RNA in the blood does not detect viral copies already integrated into resting cells. Measuring HIV DNA in the cells often doesn’t provide an accurate picture either, since the cheapest and most available technologies cannot distinguish between harmless fragments of HIV DNA and intact HIV DNA, only the latter of which is capable of replicating itself. 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 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.
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.
Last updated September 2016.