Published in PLOS One on 2026-06-02, this study is presented as an attributed evidence briefing. The excerpts below are the original researchers’ words, reproduced under their Creative Commons Attribution licence. Health Signal has selected the abstract and, where needed, opening background paragraphs; the complete methods, results, limitations and references remain in the linked paper.
Original authors: Alexandra Poeschla, Abduljewad Wele, Elizabeth Nalintya, Biyue Dai, David B. Meya, David R. Boulware, Radha Rajasingham
Source: PLOS One • DOI 10.1371/journal.pone.0349854
Read the complete primary study ↗ · Creative Commons Attribution licence
From the researchers
Abstract
Cryptococcal meningitis causes an estimated 19% of AIDS-related deaths globally and is the leading cause of meningitis in adults with HIV. Subclinical infection with cryptococcal antigen (CrAg) is detectable in plasma, and CrAg titer of>=1:160 is predictive of meningitis or death. We evaluated if plasma CrAg titer changed over time in Uganda with the expansion of national CrAg screening programs and antiretroviral (ART) access.
We prospectively screened adults with advanced HIV disease (CD4 ≤ 200 cells/μl) for CrAg from 2017 through 2022 using the lateral flow assay and assessed median plasma CrAg titer.
From November 2017 to May 2022, 436 adults with advanced HIV disease had a positive plasma CrAg test. The median CD4 + cell count was 45 [IQR: 21,94] cells/µL, and median plasma CrAg titer was 1:80 [IQR: 10,1280]. Analysis of median quarterly CrAg titer from 2017–2022 demonstrated a non-statistically significant positive trend in CrAg titer (tau = 0.385, p = 0.086). There was a statistically significant decline in the percentage of participants taking ART at the time of screening (p < 0.001), with 58% reporting never having taken ART in 2022.
Despite expansion of CrAg screening and ART, median annual CrAg titers have not decreased between 2017 and 2022 in Uganda. Contrary to national reporting of expanded access to ART, our study population had higher rates of ART-naïve status over time, suggesting ongoing late presentation to care for people with advanced HIV disease. In addition, the presence of ART-experienced patients in our study population suggests challenges with treatment adherence and retention. Cryptococcosis persists, and despite public health efforts, people are not presenting to care earlier in their disease course. Continued refinement of CrAg screening programs is needed to reduce AIDS-related deaths.
Background
Cryptococcosis causes an estimated 19% of AIDS-related deaths globally and is the leading cause of meningitis in adults living with HIV in Africa [1]. Subclinical infection with cryptococcal antigen (CrAg) in the bloodstream is a risk factor for meningitis and death [2]. The World Health Organization (WHO) recommends CrAg screening for adults with a CD4 cell count <100 cells/µL and pre-emptive fluconazole treatment for people identified as plasma CrAg-positive [3]. At least 19 African countries have now implemented national CrAg screening programs for people with advanced HIV disease [4]. In Uganda, the national CrAg screening program for adults with a CD4 cell count <100 cells/µL was implemented in 2016 [5], with a conditional recommendation to expand this screening to all people with CD4 cell counts <200 cells/µL. CrAg screening programs identify people earlier in their course of cryptococcal disease and result in improved survival [3].
Reading this evidence
Use the full paper to check the study design, participant selection, comparator and outcome definitions before drawing a practical conclusion. An association does not by itself show cause and effect. A reported performance measure needs its denominator and uncertainty. A finding from a particular facility, sample or time period should retain that scope when it is discussed elsewhere.
This briefing makes the source accessible within the wider public health desk. It does not assess an individual patient or certify a product. When considering relevance to another health system, examine the original authors’ account of context and limitations, then seek local implementation evidence. The related reporting below provides other studies to read alongside this one; it is a topic connection, rather than a claim that their results are directly comparable.
© 2026 Alexandra Poeschla, Abduljewad Wele, Elizabeth Nalintya, Biyue Dai, David B. Meya, David R. Boulware, Radha Rajasingham. Excerpts reproduced under CC BY. Selection, formatting and contextual notes by Health Signal. The researchers are the authors of the source study, not members of Health Signal’s staff.
Explore connected evidence
- Evidence brief: Empiric tuberculosis treatment and 12-month mortality among sputum GeneXpert-negative adults living with HIV in Uganda in the era of widespread antiretroviral therapy: A prospective cohort study
- Evidence brief: Inpatient mortality and associated clinical factors among people living with HIV with cryptococcal meningitis in Uganda: A retrospective cohort study
- Evidence brief: High performance of point-of-care rapid tests for advanced HIV disease diagnosis by lay providers in Malawi: Results from a prospective diagnostic accuracy study supporting decentralized advanced HIV disease screening
