The International HIV Controllers Study is a collaborative effort among scientists, healthcare professionals and the community to study HIV infected people who have been able to maintain low viral loads without the use of medications.
This study brings together HIV researchers from around the world and promotes increased dialogue and collaboration about this remarkable group of individuals who may hold the key to new approaches to therapy and vaccines.
Study Objectives
- Establish an international cohort of HIV-infected individuals who control HIV replication without the use of medications
- Perform a genome wide association study to determine the influence of genetic factors on HIV control
- Define the innate and adaptive immune responses in HIV Controllers
- Describe the patterns of viral evolution in situations of control of HIV
- Identify the contribution of viral fitness to viral control
Progress
Previews of Investigations..Investigators: Kwon, Walker
Title of Project: Gut mucosal immunity to HIV-1 in controlled and progressive infection
Progress Report:
The immune response to HIV has largely been studied in the most accessible compartment- the peripheral blood, which contains only 2-3% of all immune cells. In contrast, at least half of the body's T and B cells reside in gut associated lymphoid tissue (GALT). Unfortunately, the characterization of HIV specific immune responses in the gut has remained incomplete, in large part due to the technical challenges of assaying the small number of immune cells that can be obtained from biopsies of the colon and small bowel. We are using novel, state-of-the-art functional assays developed with Dr. Chris Love at MIT to simultaneously measure multiple immune functions of individual cells obtained from gut biopsies. We are using these techniques to better understand the immune response against HIV in the gut of individuals who have progressive HIV disease and those who are able to spontaneously control disease in the absence of antiretroviral therapy.
Investigators: Pereyra, Heckerman, Walker
Title of Project: Epitope specific CD8 T-Cell responses in HIV controllers
Progress Report:
CD8+ lymphocytes play a role in the immune system's ability to eliminate cells that have been infected with the HIV virus. Preliminary studies allowed us to identify the specific HIV protiens that HIV controller's CD8+ lymphocytes target to control the virus. These studies have provided clues that help us understand how certain inherited molecules (HLA alleles) affect a person's ability to control the virus. By identifying the specific HIV proteins that are targeted in individuals that control the HIV virus, we hope to inform the design of an HIV vaccine.
Concept Sheet submitted 04/01/2009
Investigator: Annapuma Vyakamam
Title of Project: Assessing the clinical utility of plasma ps20 as a novel marker of HIV disease progression
Progress Report:
Our laboratory has identified a potential novel marker of HIV disease progression (WFDC1/ps20) that may provide fresh insight to disease mechnisms of HIV infection. We have shown that ps20 has two important and diverse functions that may impact pathogenesis of HIV infection. First, ps20 can enhance HIV infection in CD4 T-cells and thereby drive CD4 T-cell loss. Second, ps20 has homeostatic potential and limits bacterial lipopolysaachride driven immune activation, which is now recognized to be an important mechnaism for immune activation in HIV infected subjects. Our hypothesis is that ps20 levels may fall with increasing virus replication and this fall may contribute to immune activation and disease progression in the chronic stage of HIV infection. Our aim is to test this hypothesis in plasma samples available from the NIH controller cohort. If validated, plasma ps20 levels may be explored as a novel biomarker of HIV disease progression.
Concept Sheet submitted 03/01/2009