Immune reconstitution disease: recent developments and implications for antiretroviral treatment in resource-limited settings

Abstract

We review literature published over the past 2 years regarding the immunopathogenesis, epidemiology, clinical spectrum and outcomes of immune reconstitution disease in patients receiving antiretroviral treatment. Particular attention is drawn to data relevant to resource-limited settings. In high-income countries, immune reconstitution disease occurs in association with a largely predictable spectrum of pathogens, including the herpesviruses, Mycobacterium tuberculosis and Mycobacterium avium complex, Cryptococcus neoformans and hepatitis viruses. Dermatological manifestations are most frequent. In resource-limited settings, patients accessing antiretroviral treatment programmes typically have advanced immunodeficiency, which increases risk of immune reconstitution disease. M. tuberculosis and C. neoformans have emerged as the key causes of morbidity and mortality associated with immune reconstitution disease. An increasing number of 'tropical' infections, including leprosy, schistosomiasis, strongyloidiasis, leishmaniasis, histoplasmosis and many nontuberculous mycobacteria, are also now recognised to provoke immune reconstitution disease but the overall spectrum and relative importance of these organisms remain to be defined. Better characterisation of immune reconstitution disease in these settings is needed to enable development of guidelines regarding prevention, diagnosis and management. While immune reconstitution disease in high-income countries has been clinically and epidemiologically well described, much remains to be learned in resource-limited settings in which immune reconstitution disease is emerging as a significant cause of morbidity and mortality.