Trends in Histoplasma-Associated Immune Reconstitution Inflammatory Syndrome

Although incidence of histoplasma-associated immune reconstitution inflammatory syndrome is low, it still generates significant morbidity in people living with HIV.

A 20-year case series and literature review found that although incidence of histoplasma-associated immune reconstitution inflammatory syndrome (IRIS) was low, it still generated significant morbidity in people living with HIV (PLHIV). The findings of this review were published in Clinical Infectious Diseases.

Using data from a retrospective multicentric study conducted in French Guiana from January 1997 to September 2017, the study investigators identified a population of PLHIV who presented with an episode of histoplasmosis within 6 months after antiretroviral therapy initiation. Researchers implemented a case definition for IRIS after obtaining a consensus from 2 experts.

In total, 22 cases were included, with an overall incidence rate of 0.74 cases per 1000 person-years HIV-infected (95% CI, 0.43-1.05). The mean age and sex ratio of the cases were 40.5 years and 1:4, men:women. At the time of IRIS onset, the median CD4 count was 128 cells/μL (range, 6-529 cells/μL); at the time of ART initiation, the median CD4 count was53.5 cells/μL (range, 22.5-146.0 cells/μL). Median time to IRIS after antiretroviral therapy initiation was 11 days, and the main clinical presentation was fever, without any specific pattern, and disseminated disease. Two cases were reported as severe, however partial or complete recovery at 1 month was achieved by all participants. A further 22 similar cases were identified in the literature.

The study investigators identified several limitations to the study, as a result of its retrospective design, including missing data and difficulties in reviewing older files because of poor storage conditions. Together, these may have led to underestimation of the incidence of cases, severe forms of the condition, or deaths. In addition, 4 cases of coinfections with pathogens often responsible for IRIS were included, but the study investigators attempted to minimize classification bias with rigorous case definitions and expert agreement.

On the basis of the descriptions of the 44 histoplasmosis-associated IRIS cases identified, researchers advised that in endemic areas, “physicians should be aware of histoplasmosis-associated IRIS and its potential severe developments where the patients’ vital prognosis is at risk.” They further noted that diagnostic improvements for the detection of Histoplasma capsulatum are needed to screen asymptomatic or pauci-symptomatic PLHIV before the start of antiretroviral therapy. Finally, the study authors also recommended that the World Health Organization, as well as national HIV guidelines, should consider adding histoplasmosis to their advanced HIV disease package of care.

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Melzani A, De Reynal De Saint Michel R, Ntab B, et al. Incidence and trends in immune reconstitution inflammatory syndrome associated with Histoplasma capsulatum among people living with HIV: a 20-year case series and literature review [published online March 28, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz247