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Observational Study
. 2025 Aug 13;25(1):1014.
doi: 10.1186/s12879-025-11417-0.

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

Fenqi Da #  1   2 , Yi Cao #  1   2   3 , Pengle Guo  1   2 , Yeyang Zhang  1   2 , Yaozu He  1   2 , Quanmin Li  1   2 , Weiran Tan  1   2 , Huijun Hou  1   2 , Xiaoping Tang  1   2   4 , Heping Zhao  5   6 , Linghua Li  7   8
Affiliations
Observational Study

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

Fenqi Da et al. BMC Infect Dis. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: ART; CrAg; PLHIV; Positivity.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the institutional review board of the Guangzhou Eighth People’s Hospital (Approval number: 202034167). Informed consent was signed by all participants at enrollment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study flow chart
Fig. 2
Fig. 2
Correlation between CD4+ T cell counts and CrAg positivity in PLHIV. (a, b and c) CrAg positivity rates among PLHIV stratified by different baseline CD4+ T cell count. (d) Distribution of baseline CD4+ T cell counts among CrAg-positive PLHIV (n=75). *, 0.01≤ P＜0.05. NS, not significant (P ≥ 0.05).
Fig. 3
Fig. 3
Correlation between CD4 + T cell counts and CrAg positivity in ART-naïve PLHIV. (a) CrAg Positivity rates across baseline CD4 + T cell count categories. (b) Distribution of baseline CD4 + T cell counts among CrAg-positive PLHIV (n = 19). NS, not significant (P ≥ 0.05)
Fig. 4
Fig. 4
Correlation between CD4 + T cell counts and CrAg positivity in ART-experienced PLHIV. (a) CrAg Positivity rates across current CD4 + T cell count categories. (b) Distribution of current CD4 + T cell counts among CrAg-positive PLHIV (n = 56). NS, not significant (P ≥ 0.05)
Fig. 5
Fig. 5
CrAg positivity rates stratified by ART duration. (a, b) CrAg positivity rates among PLHIV stratified by different ART duration. **, 0.001 ≤ P < 0.01. ***, P < 0.001
Fig. 6
Fig. 6
Diagnosis of cryptococcal disease in CrAg-positive PLHIV
See this image and copyright information in PMC

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