August 15, 2025Open Access

Factors associated with cryptococcal capsular antigen positivity among people living with HIV: a retrospective observational cohort study

FDFenqi DaGuangzhou Eighth People's Hospital YCYi CaoHebei Medical University PGPengle GuoGuangzhou Mechanical Engineering Research Institute (China)

Key Points

CrAg positivity was 5.1%, with 94.7% of positive individuals having CD4 counts ≤ 200 cells/μl.
Significant association with shorter ART duration was observed, highlighting risks in ART-experienced PLHIV.
Low CD4 T cell counts, shorter ART duration, and opportunistic infections increased CrAg positivity rates significantly.
Screening for serum CrAg in PLHIV with CD4 counts ≤ 200 cells/μl may reduce cryptococcosis-related mortality.

Abstract

Cryptococcosis, which is caused by Cryptococcus, is an aggressive fungal disease posing a high mortality risk among people living with HIV (PLHIV). However, factors associated with cryptococcal capsular antigen (CrAg) positivity among PLHIV remain unclear. We recruited PLHIV from the Guangzhou Eighth People's Hospital between March 2018 and December 2019. Serum CrAg was qualitatively detected using Lateral Flow Assay. Fungal culture and pathological examinations were performed on cerebrospinal fluid. Chi-squared tests and multivariable logistic regression were used to identify factors associated with CrAg positivity. A total of 1478 PLHIV were included, among whom 297 (20.1%) were antiretroviral therapy-naïve (ART-naïve), 1181 (79.9%) were ART-experienced. The median baseline CD4 + T cell count was 43 cells/μl (interquartile range IQR:13-117). The overall CrAg positivity rate was 5.1%, with 94.7% of CrAg-positive individuals having baseline CD4 + counts ≤ 200 cells/μl. CrAg positivity was 6.4% among ART-naïve and 4.7% among ART-experienced PLHIV. Notably, within the ART-experienced group, CrAg-positive PLHIV displayed lower baseline and latest CD4 + T cell counts than those in CrAg-negative PLHIV. CrAg status was significantly associated with shorter ART duration (≤ 1 year vs. > 2 year: adjusted odds ratio aOR, 2.53; 95% confidence interval CI, 1.20-5.34. 1-2 year vs. > 2 year: 4.61, 2.10-10.12) and other OIs (2.56, 1.41-4.63) among ART-experienced PLHIV. A considerable CrAg positivity rate was observed among both ART-naïve and ART-experienced PLHIV. CD4 + T cell count ≤ 200 cells/μl, shorter ART duration, and presence of other opportunistic infections were all significantly associated with CrAg positivity. These findings support extending serum CrAg screening to all PLHIV with CD4 + counts ≤ 200 cells/μl, regardless of ART status, to improve early detection and reduce cryptococcosis-related mortality.

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