HIV-1 and the immune response to TB

Abstract

TB causes 1.4 million deaths annually. HIV-1 infection is the strongest risk factor for TB. The characteristic immunological effect of HIV is on CD4 cell count. However, the risk of TB is elevated in HIV-1 infected individuals even in the first few years after HIV acquisition and also after CD4 cell counts are restored with antiretroviral therapy. In this review, we examine features of the immune response to TB and how this is affected by HIV-1 infection and vice versa. We discuss how the immunology of HIV-TB coinfection impacts on the clinical presentation and diagnosis of TB, and how antiretroviral therapy affects the immune response to TB, including the development of TB immune reconstitution inflammatory syndrome. We highlight important areas of uncertainty and future research needs.

Keywords: ART; HIV; TB; TB-IRIS; TB-associated immune reconstitution inflammatory syndrome; antiretroviral therapy; diagnosis; immunity; immunopathology; tuberculosis.

Figure 1. Major risk factors for TB disease

Environmental and host factors influence Mycobacterium tuberculosis exposure and the risk of development of active TB once infected. Young age, with increased proximity to infectious adults and a less developed immune response, confers increased risk of exposure and progression to disease. Diabetes, malnutrition, vitamin D deficiency and HIV infection impact on risk following exposure, probably by both increasing the likelihood of exposure leading to chronic infection and progression of infection to active TB. These conditions are affected by a complex interplay of host and environmental factors: for example, vitamin D deficiency occurs as a result of insufficient environmental UVB exposure and also host genetic factors that influence vitamin D metabolism. Host factors (e.g., immunosuppression with anti-TNF-α therapy) also increase risk of progression of infection to TB disease.

Figure 2. The spectrum of immune responses to TB correlates with a spectrum of outcomes of Mycobacterium tuberculosis infection

HIV infection (and mycobacterial burden) impact on risk of progression towards disease. Despite high mycobacterial burdens, characteristic inflammatory pathology (e.g., dense pulmonary consolidation and cavitation) is rare in HIV when CD4 counts are <200 cells/mm³. This may occur in those with relatively preserved CD4 counts or develop with ART, in TB-associated immune reconstitution inflammatory syndrome. ^†In HIV, evidence of T-cell memory may be lost. ART: Antiretroviral therapy.