Despite significant reductions in morbidity and mortality secondary to availability of effective combination antiretroviral therapy (cART), human immunodeficiency virus (HIV) infection still accounts for 1.5 million deaths annually. The majority of deaths occur in sub-Saharan Africa where rates of opportunistic co-infections are disproportionately high. In this review, we discuss the immunopathogenesis of five common infections that cause significant morbidity in HIV-infected patients globally. These include co-infection with Mycobacterium tuberculosis, Cryptococcus neoformans, hepatitis B virus (HBV), hepatitis C virus (HCV), and Plasmodium falciparum. Specifically, we review the natural history of each co-infection in the setting of HIV, the specific immune defects induced by HIV, the effects of cART on the immune response to the co-infection, the pathogenesis of immune restoration disease (IRD) associated with each infection, and advances in the areas of prevention of each co-infection via vaccination. Finally, we discuss the opportunities and gaps for future research.
Despite the increasing availability of combination antiretroviral therapy (cART), nearly 1.5 million deaths were attributed to human immunodeficiency virus (HIV) in 2010 (1). The immunodeficiency caused by chronic HIV infection increases the risk of co-infection with pathogens that are controlled by innate and adaptive cellular immune responses and some that are controlled by phagocytic antibody responses. Furthermore, administration of cART in the setting of HIV co-infection does not always restore the pathogen-specific immune response to normal levels.