Human genetic variation in HIV disease: beyond genome-wide association studies

Rapid expansion of genomic technologies has resulted in an unprecedented ability to interrogate the impact of human genetic variation on disease. HIV-1 infection is a unique model for studying this impact because host genetic variation influences both clinical outcome and the genetic sequence and evolution of the pathogen itself.

Several candidate gene studies have proposed novel associations with HIV acquisition and/or disease progression; however, many of these are not supported by larger genome-wide association studies. Thus, controversy remains as to which host and viral genetic factors truly impact HIV infection. Novel methods for assessing the genetic (viral and host) component of disease progression are becoming important areas of investigation.

To fully understand the impact of human genetic variation in HIV disease, the field will need to come together to set a standard for discovery of new genes. Additionally, novel avenues of investigation such as sequencing studies (to define the role of rare variants), studies of epistasis and host/viral genome interaction will be of great value.