What does the term ‘AIDS cure’ mean?
The term “cure” refers to a strategy or strategies that would 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 viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from transmitting. It is difficult to distinguish these types of cures, some are now using the term “remission”, borrowed from the cancer field. This is generally defined as the lack of readily detectable rebound of the virus for some period of time after stopping drugs. This time period is not yet defined by the scientific community.
It’s important to know that researchers are still debating and discovering what is means to be biologically cured of HIV. Although some possible cases of functional cures have been reported, it takes time to be certain that HIV can no longer cause disease, because it is known that even very low levels of virus below the limit of detection can increase the risk of certain illnesses and ultimately lead to AIDS.
What types of cure strategies are being investigated today?
There are four broad strategies being explored. Each of these strategies takes a different approach to the fundamental challenge of HIV infection—that the virus can hide out in cells that are not active and dividing. As long as the cells are not dividing, the virus isn’t copying itself and is considered to be “latent”. Cells that carry latent virus are, collectively, referred to as viral reservoirs. Most of the viral reservoir is in memory CD4+ T cells, which are designed to live in the body indefinitely. A truly effective cure will either have to eliminate these viral reservoirs or ensure that virus that gets activated from resting cells 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 and then follow up with effective killing of the infected cells. Many of the shock agents being considered are currently used as cancer treatments. The “kill” component of this one-two punch could involve a therapeutic vaccine, if an effective one can be developed or other interventions to improve the immune response to HIV.
This strategy seeks to change a person’s cells so that HIV can’t infect them. This can be done by altering the genes of a person’s immune cells. Genes are the blueprint for the cell’s architecture. An alteration that removes a key receptor or protein that HIV uses for infection can make the cell resistant to infection. Gene therapy is targeting many of the same targets used in treatment. Since HIV needs to be inside cells to copy itself, such a strategy might effectively stop HIV from spreading in the body. The most advanced gene therapy is technologically complex: it involves extracting CD4 T cells from HIV-positive individuals and then modifying them with a method that disables the gene that encodes the CCR5 receptor (which most HIV variants use as a foothold to gain entry into cells).
Stem cell transplants
Hematopoietic stem cells, produced in bone marrow, are the source of all blood cells in the body. Stem cell transplants are used to treat life threatening illnesses such as cancer. They carry a high risk of side effects. In the notable case of Timothy Brown, who was apparently cured of HIV, he received a stem cell transplant for cancer treatment. His transplant contained cells that could not be infected by HIV because they lacked a key receptor (CCR5) on their surface. 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 HIV-infected cells. Stem cell transplants are a last resort for people with both cancer and HIV. This strategy is not scalable.
Therapeutic vaccines are designed to boost or induce immune responses against HIV in someone who is already infected with the virus. Most of these vaccines are aimed at increasing the potency of the natural killers of HIV (e.g., HIV-specific CD8+ T cells and NK cells). The hope is that vaccine-induced immune responses can contribute to control of the virus in the absence of antiretroviral treatment, and perhaps also help eliminate latently infected cells.
What are challenges related to cure research?
There are many issues that make cure research difficult. First, there is no clear way to measure the HIV reservoir. The two leading approaches are to measure the number of HIV RNA copies in the blood, or the number of HIV DNA copies in cells. Just measuring HIV RNA in the blood does not detect the viral copies that have already integrated into resting cells. Measuring DNA doesn’t necessarily give an accurate picture, either, since the cheapest and most available technologies cannot distinguish replication-competent virus. A more precise assay, the quantitative viral outgrowth assay, requires the use of large numbers of cells and cannot be done with a simple blood draw.
A second major challenge is that cure strategies currently under investigation carry unknown risks and benefits. Figuring out how to communicate theses unknowns to potential trial participants will be an important part of any cure clinical trial. In order to test whether a person has been cured, they need to stop effective antiretroviral treatment so that viral rebound, if any, can be measured. There are no standardized guidelines for how to time such “treatment interruptions” so that they 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.
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.
Last updated March 2015.