HIV This Week

Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther 2007 May 8;4:9.

The immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients initiating antiretroviral therapy (ART) results from restored immunity to specific infectious or non-infectious antigens. A paradoxical clinical worsening of a known condition or the appearance of a new condition after initiating therapy characterizes the syndrome. Potential mechanisms for the syndrome include a partial recovery of the immune system or exuberant host immunological responses to antigenic stimuli. The overall incidence of IRIS is unknown, but is dependent on the population studied and its underlying opportunistic infectious burden. The infectious pathogens most frequently implicated in the syndrome are mycobacteria, varicella zoster, herpes viruses, and cytomegalovirus (CMV). No single treatment option exists and depends on the underlying infectious agent and its clinical presentation. Prospective cohort studies addressing the optimal screening and treatment of opportunistic infections in patients eligible for ART are currently being conducted. These studies will provide evidence for the development of treatment guidelines in order to reduce the burden of IRIS. Murdoch and colleagues review the available literature on the pathogenesis and epidemiology of IRIS, and present treatment options for the more common infectious manifestations of this diverse syndrome and for manifestations associated with a high morbidity.

Editors’ note: When antiretroviral treatment is initiated, patients with an unrecognized underlying infection may develop an immune reconstitution inflammatory syndrome as their immune systems rev up to face an unwelcome guest that has been hanging around. Identifying these infections and treating them specifically is important but guidelines are needed on the sequencing of this treatment vis-à-vis antiretroviral therapy initiation and relevant monitoring for early detection of inflammatory problems.

Lawn and colleagues’ objective was to determine the burden and impact of immune reconstitution disease (IRD) associated with tuberculosis (TB) among patients initiating antiretroviral treatment (ART) in sub-Saharan Africa. The authors used a retrospective analysis of a study cohort enrolled over 3 years within a community-based ART service in South Africa. Patients receiving treatment for TB at the time ART was initiated (n = 160) were studied. Cases of TB-associated IRD during the first 4 months of ART were ascertained. Results showed that the median baseline CD4 cell count was 68 cells/microl [interquartile range (IQR), 29-133 cells/microl) and ART was initiated after a median of 105 days (IQR, 61-164 days) from TB diagnosis.  Although IRD was diagnosed in just 12% (n = 19) of patients overall, IRD developed in 32% (n = 12) of those who started ART within 2 months of TB diagnosis. Pulmonary involvement was observed in 84% (n = 16) and intra-abdominal manifestations were also common (37%). Overall, 4% (n = 7) of the cohort required secondary level health-care for IRD and two (1%) patients died. In multivariate analysis, risk of IRD was strongly associated with early ART initiation and low baseline CD4 cell count. Of patients with CD4 counts < 50 cells/microl, the proportions who developed IRD following initiation of ART within 0-30, 31-60, 61-90, 91-120 and > 120 days of TB diagnosis were 100%, 33%, 14%, 7% and 0%, respectively. The authors conclude that the risk of TB-associated IRD in this setting is very high for those with low baseline CD4 cell counts initiating ART early in the course of anti-tuberculosis treatment. However, most cases were self-limiting; overall secondary health-care utilization and mortality risk from IRD were low.

Editors’ note: In this study, immune reconstitution inflammatory syndrome (IRIS) developed in a third of tuberculosis patients who started antiretroviral treatment within 2 months of TB diagnosis. The lower the CD4 count at antiretroviral treatment initiation the higher the risk of IRIS. The real dilemma for such patients and their physicians is how long to wait before starting antiretroviral treatment. This study suggests at least a 90 day wait or longer but more specific studies are ongoing now to determine the ideal length.