Association of Antibody Immunity With Cryptococcal Antigenemia and Mortality in a South African Cohort With Advanced Human Immunodeficiency Virus Disease.

Background: Asymptomatic cryptococcal antigenemia (positive blood cryptococcal antigen [CrAg]) is associated with increased mortality in individuals with human immunodeficiency virus (HIV) even after adjusting for CD4 count and despite receiving antifungal treatment. The association of antibody immunity with mortality in adults with HIV with cryptococcal antigenemia is unknown.
Methods: Cryptococcal capsular glucuronoxylomannan (GXM)- and naturally occurring β-glucans (laminarin, curdlan)-binding antibodies were measured in blood samples of 197 South Africans with HIV who underwent CrAg screening and were followed up to 6 months. Associations between antibody titers, CrAg status, and all-cause mortality were sought using logistic and Cox regression, respectively.
Results: Compared with CrAg-negative individuals (n = 130), CrAg-positive individuals (n = 67) had significantly higher IgG1 (median, 6672; interquartile range [IQR], 4696-10 414 vs 5343, 3808-7722 μg/mL; P = .007), IgG2 (1467, 813-2607 vs 1036, 519-2012 μg/mL; P = .01), and GXM-IgG (1:170, 61-412 vs 1:117, 47-176; P = .0009) and lower curdlan-IgG (1:47, 11-133 vs 1:93, 40-206; P = .01) titers. GXM-IgG was associated directly with cryptococcal antigenemia adjusted for CD4 count and antiretroviral therapy use (odds ratio, 1.64; 95% confidence interval [CI], 1.21 to 2.22). Among CrAg-positive individuals, GXM-IgG was inversely associated with mortality at 6 months adjusted for CD4 count and tuberculosis (hazard ratio, 0.50; 95% CI, .33 to .77).
Conclusions: The inverse association of GXM-IgG with mortality in CrAg-positive individuals suggests that GXM-IgG titer may have prognostic value in those individuals. Prospective longitudinal studies to investigate this hypothesis and identify mechanisms by which antibody may protect against mortality are warranted.
Competing Interests: Potential conflicts of interest. N. P. G. reports grants or contracts from NIH, UK MRC, Gates Foundation, CDC, and NHLS Research Trust (paid to institution); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the South African HIV Clinicians Society (paid to author); a role as president and council member of FIDSSA; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Immy– CrAg LFA strips (paid to institution). T. S. H. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead Sciences and Pfizer (paid to author). J. N. J. reports grants from the CDC; speaker fees from Gilead; participation on a data and safety monitoring board as the TSC chair for ASTRO, HARVEST, ARTIST, ACACIA, and CASTLE; and received a drug donation for a clinical trial from Gilead Sciences, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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