The International HIV Controllers Study

The goal of the International HIV Controllers Study is to help scientists understand why some people are able to control HIV infection without the need to take any medications, and to reveal the biological basis of this exquisite viral control. These findings could lay the foundation for novel therapies or vaccines that benefit a wide range of HIV patients.

The project is a multinational collaboration involving scientists at the Massachusetts General Hospital (MGH); the Ragon Institute of MGH, MIT and Harvard; and the Broad Institute of MIT and Harvard, among others.

At the Broad Institute, two key projects are currently underway:

1. Explore the role of host genetics by studying the influence of inherited genetic factors on HIV control (host genetics),
2. Understand the contributions of viral genetics by describing the patterns of viral evolution during HIV control in response to host immune pressures.

These projects are led by Paul de Bakker and Matthew Henn, respectively.

Host genetics
Inherited genetic variation plays a critical role in human disease. With detailed knowledge about the patterns of common genetic variation in the human genome and the development of high-throughput technologies, it has become possible to survey vast numbers of genetic variants and to comprehensively test these variants for their role in disease. The approach, known as a genome-wide association study, (GWAS) is transforming scientists’ knowledge of a wide range of human diseases, including type 2 diabetes, heart disease, Crohn's disease, multiple sclerosis, bipolar disorder, and autism, among many others.

Scientists working on the International HIV Controllers Study are using the GWAS approach to compare DNA from HIV controllers (patients who can control the disease without medication) and HIV progressors (patients who require treatment).

Given that the genetic effects of associated genes are likely to be modest, there is an ongoing need to enroll more patients in this study. For more information about how to enroll, click here.

Viral genetics
Just as individuals’ DNA can influence health, so can the precise genetic makeup of infectious agents, including viruses. In HIV, the virus that causes the disease can alter its RNA to avoid detection by the host immune system. This viral evolution — which occurs both within and across individual patients — is one of the major hurdles to the design of an effective vaccine.

To understand how viral evolution contributes to the disease in general and to HIV control in particular, project scientists are working to decode viral DNA from HIV patients using whole genome sequencing.