Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals

Immune reconstitution disease (IRD) in HIV-infected patients is an adverse consequence of the restoration of pathogen-specific immune responses during the initial months of highly active antiretroviral treatment (HAART). Previously subclinical infections are "unmasked" or pre-existing opportunistic infections clinically deteriorate as host immunopathological inflammatory responses are "switched on". IRD is most frequently associated with mycobacterial infections. Our literature search identified 166 published cases of IRD associated with mycobacterial infections. We review the underlying immunological mechanisms, difficulties surrounding case definition and diagnosis, the wide diversity of clinical manifestations, and treatment. The importance of screening patients for mycobacterial disease before starting HAART and the critical impact of the timing of commencement of HAART in patients receiving treatment for tuberculosis are highlighted. We also discuss the problem of IRD associated with mycobacterial diseases in developing countries where tuberculosis prevalence is high and access to HAART is currently expanding.