P-1959. Duration and Quantification of Histoplasma capsulatum Antigenuria During Treatment of Histoplasmosis in Patients by Immune Status

TL;DR

The study examines how long Histoplasma capsulatum antigens remain in urine during treatment for histoplasmosis in patients with different immune statuses.

Contribution

It provides new data on antigen clearance times and levels in non-HIV immunocompromised patients, which could inform updated treatment guidelines.

Findings

Transplant patients had the longest median time to antigen negativity (22.7 months).

PLWH had the highest median antigen levels at diagnosis (20 ng/mL).

Over 80% of patients with antigenuria at 2 years were in transplant or biologic immunosuppression groups.

Abstract

Despite its classic association with HIV, modern cohorts of histoplasmosis are overwhelmingly in those with non-HIV-associated immunocompromise, such as biologic immunosuppression or solid organ transplantation. However, treatment guidelines are largely extrapolated from 30-year-old studies of patients with HIV.

We conducted a single-center, retrospective study of adult patients with varying immune status diagnosed with histoplasmosis by positive antigen testing and undergoing treatment between 2002 to 2021. Time to H. capsulatum antigen negativity was calculated and compared between immune status groups using competing risk analysis. Per-patient, mean antigen levels were compared at 6mo intervals from diagnosis.

95 patients treated for histoplasmosis had varying immunocompromise: immunocompetent (n=21), biologic immunosuppression (n=18), people living with HIV (PLWH) (n=18), any transplant (n=28), and other (n=10) – primarily prednisone with methotrexate or other disease modifying therapy (7/10). Median time to antigen negativity, accounting for competing risk of death by group was: transplant - 22.7mo, PLWH - 16.9mo, biologics - 12.9mo, other immunocompromise - 13.2mo, and immunocompetent - 6.8mo (Figure 1). Median antigen level at diagnosis was highest in PLWH (20ng/mL [Q1: 13.5, Q3: 20]) and transplant patients (9.2ng/mL [4.1, 15.9]) versus the other groups – immunocompetent: (2.4ng/mL [0.5, 6.0]), biologics: (2.8ng/mL [2.0, 4.9]), other: (3.1ng/mL [1.6, 15.6]) (Figures 2 & 3). Of patients not deceased or lost to follow-up at 24mo, 31.6% (6/19) of transplant patients and 28.6% (4/14) of biologic patients had positive antigen testing versus 0% (0/7) of PLWH, 6.2% (1/16) of immunocompetent patients and 20% (1/5) of other immunocompromise patients.

Median time to antigen negativity was highest in transplant patients and PLWH and intermediate in biologic and other immunocompromise groups relative to immunocompetent patients. More than 80% of patients with antigenuria at 2yrs were in the transplant or biologic groups. Duration and magnitude of antigen positivity varied across immune status, impacting length of treatment for histoplasmosis.

Andrej Spec, M.D., MSCI, Astellas Global Development Pharma, Inc: Grant/Research Support|Cidara: Grant/Research Support|Mayne Pharma: Grant/Research Support|Scynexis: Grant/Research Support

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