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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.

BACKGROUND
Histoplasmosis is among the main AIDS-defining conditions in endemic areas. Although histoplasmosis has a worldwide distribution, histoplasmosis-associated immune reconstitution inflammatory syndrome (IRIS) in people living with HIV (PLHIV) is rarely reported.This study aimed to describe the incidence and features of histoplasmosis-associated IRIS in a cohort of PLHIV.


METHOD
A retrospective multicentric study was conducted in French Guiana from 01/01/1997 to 09/30/2017. The target population was represented by PLHIV who presented an episode of histoplasmosis within six months after antiretroviral therapy initiation. We used a consensual IRIS case definition, submitted to the agreement of 2 experts. Each case was described using a standardized questionnaire and all patients gave informed consent.


RESULTS
Twenty two cases of histoplasmosis-associated IRIS were included (14 infectious/unmasking and 8 paradoxical) with an overall incidence rate of 0.74 cases per 1000 person-years HIV-infected (CI95%: 0.43-1.05). Mean age was 40.5 years. Sex ratio M:F was 1.4. Median time to IRIS was 11 days [7-40] after antiretroviral therapy initiation. The main clinical presentation was fever, without any specific pattern, and disseminated disease. We reported 2 severe cases and partial or complete recovery at one month was the rule. Twenty-two cases were identified in the literature with similar characteristics.


DISCUSSION
Histoplasmosis-associated IRIS incidence was low but generated significant morbidity in PLHIV. In endemic areas, screening for latent or subclinical histoplasmosis should be implemented before antiretroviral therapy initiation.