Blood and biological samples, generously provided by anonymous volunteers, helped us to better understand the role of a type of CD4 T-cell that expresses a molecule on its surface called CCR6 on HIV reservoirs in the gut and in blood. These results were published in the prestigious scientific journal AIDS in January 2017.
HIV reservoirs are the cells and tissues where HIV lies dormant (“asleep”), even when a person is taking effective antiretroviral therapy and has an undetectable viral load. While antiretroviral therapy is generally successful in controlling the viral load in people with HIV and preventing progression to AIDS, currently available antiretrovirals don't completely kill the sleeping HIV-infected cells. A very small amount of virus remains dormant in these HIV reservoirs, and is able to restart HIV replication if the person living with HIV goes off treatment. Research to cure HIV must target all cell reservoirs.
1) What was the goal of our study?
In a person with an undetectable viral load, HIV remains in only a very small fraction of the CD4 T-cells (a viral reservoir), and also in other types of cells. The goal of this study was to find very specific markers on the surface of CD4 T-cells. This marker would help us to identify the specific type of CD4 T-cells that are reservoirs of dormant HIV infection in the gut and in blood. Since we have known for many years that some kinds of CD4 T-cells in the intestine are preferred targets of HIV infection, we focused our research on the CCR6 molecule, which helps CD4 T-cells migrate from the blood to the intestine.
2) How is this study related to a cure for HIV? or to HIV prevention?
The identification of CCR6 molecules in a large portion of HIV-infected CD4 T-cells in participants with an undetectable viral load allows us to move our research toward the discovery of new, targeted treatment and prevention strategies. Treatment strategies would be given in addition to antiretroviral therapy to reduce the number of these especially prominent viral reservoirs. These treatments would specifically target CD4 T-cells with the CCR6 molecule carrying dormant HIV. This is an important step toward a cure for HIV. Blocking this surface marker or editing the cells safely to disrupt it might help prevent people from becoming infected or to prevent increasing the number of infected cells.
3) Why are participant samples important to this research?
Matched blood samples and colon biopsies from participants living with HIV were essential for us to identify specific types of CD4 T-cells, some which expressed the CCR6 molecule, and some which did not. These matched samples also helped us to measure the amount of HIV in an individual’s blood and compare it to the amount in the tissue of their colon.
4) What was learned? What next?
This study demonstrated that dormant HIV can be found in specific types of CD4 T-cells in the blood and colon tissue of people with an undetectable viral load more prominently than other kinds of cells. The CCR6 molecule may be used as a target for new HIV therapies, added to a person’s existing antiretroviral therapy, to further purge HIV-infected cells from the body. We still need to learn more about whether this marker is completely unique or not.