Higher blood neutrophil counts are associated with a significantly increased risk for mortality in people living with HIV (PLWHIV) with cryptococcal meningitis, according to a study published in PLoS One.1

Cryptococcosis is seen primarily in patients with dysfunctions in adaptive immunity, and not in patients with neutropenia.2 As a result, the effect neutrophil counts have during cryptococcal infection is still debated. Therefore, researchers in this study examined the association between blood neutrophil counts and outcomes in terms of mortality, the incidence of bacterial infections, and hospitalization in PLWHIV with cryptococcal meningitis.1

Data from 801 participants who were enrolled in either the Cryptococcal Optimal ART Timing (COAT; n=238) trial or the Adjunctive Sertraline for Treatment of Cryptococcal Meningitis (ASTRO-CM; n=563) trial were used in this analysis. Neutrophil levels were obtained at the time of cryptococcal meningitis diagnosis in both trials, as well as in subsequent weeks for participants in the COAT trial only. Three groups were categorized by baseline neutrophil count (<1000, 1001-3500, and >3500 cells/mm3). Absolute neutropenia was defined as neutrophil count <1000 cells/mm3.

The median blood neutrophil count was 2100 (interquartile range, 1400-3300 cells/mm3). The 30-day mortality was 31%, 31%, and 51% with baseline neutrophil counts <1000, 1001 to 3500, and >3500 cells/mm3, respectively (P <.001). The percentage of deaths related to sepsis and tuberculosis were not significantly different between the baseline neutrophil groups; neither was the incidence (within 30 days) of infections and tuberculosis.

After adjusting for sex, Glasgow coma scale, antiretroviral therapy status, cerebrospinal fluid (CSF) opening pressure, and CSF quantitative culture, baseline neutrophil count was positively associated with 30-day mortality (hazard ratio [HR], 1.09; 95% CI, 1.04-1.13 per 1000 cells/mm3 increase; P < .001). Patients with baseline absolute neutrophil counts ≤1000 cells/mm3 did not have increased risk for 30-day mortality compared with those with baseline neutrophils of 1001 to 3500 cells/mm3. However, mortality was 2-fold more likely in patients with a neutrophil count >3500 cells/mm3 compared with participants with baseline neutrophil of 1001 to 3500 cells/mm3 (HR, 1.85; 95% CI, 1.40-2.44; P <.001).

In the 12-month follow-up of participants from the COAT trial, researchers found that the strong association between time-updated neutrophil counts (per 1000 cells/mm3 increase) and mortality remained significant (adjusted HR, 1.16; 95% CI, 1.09-1.24; P <.001). There was no notable association with time-updated neutrophils and re-hospitalization.

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Although increased mortality was associated with higher blood neutrophil counts, researchers noted that the “mechanism is not clear, and the pathophysiology is unknown.”

They concluded, “Neutrophils role requires further investigation as to whether this may be a mediator directly contributing to mortality or merely a marker of underlying pathologies that increase mortality risk.”

References

1. Musubire AK, Meya DB, Rhein J, et al; COAT and ASTRO trial teams. Blood neutrophil counts in HIV-infected patients with cryptococcal meningitis: association with mortality. PLoS One. 2018;13(12):e0209337.

2. Davis JM, Huang M, Botts MR, Hull CM, Huttenlocher A. A zebrafish model of cryptococcal infection reveals roles for macrophages, endothelial cells, and neutrophils in the establishment and control of sustained fungemia. Infect Immun. 2016;84(10):3047-3062.