Immunogenetics of HIV and HIV associated tuberculosis

Tuberculosis (TB) is the frequent major opportunistic infection in HIV-infected patients, and is the leading cause of mortality among HIV-infected patients. Genetic susceptibility to TB in HIV negative subjects is well documented. Since coinfections can influence the way in which immune system respond to different pathogens, genetic susceptibility to TB in HIV patients might also change. Studies from India and other parts of the world have shown that genetic susceptibility to TB is influenced by HIV infection. In the present review, we emphasize the role of genetic factors in determining susceptibility to HIV infection, disease progression and development of TB in HIV-infected patients. Polymorphisms in human leukocyte antigen (HLA), MBL2, CD209, vitamin D receptor, cytokine, chemokine and chemokine receptor genes have been shown to be associated with development of TB in HIV patients. However, the results are inconclusive and larger well-defined studies with precise clinical data are required to validate these associations. Apart from candidate gene approach, genome-wide association studies are also needed to unravel the unknown or to establish the previously reported genetic associations with HIV associated TB. Despite the preliminary status of the reported associations, it is becoming clear that susceptibility to development of TB in HIV patients is influenced by both environmental and genetic components. Understanding the genetic and immunologic factors that influence susceptibility to TB in HIV patients could lead to novel insights for vaccine development as well as diagnostic advances to target treatment to those who are at risk for developing active disease.