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Multicenter Study
. 2025 Feb 4;231(1):e82-e90.
doi: 10.1093/infdis/jiae374.

A Prospective Evaluation of the Diagnostic Accuracy of the Point-of-Care VISITECT CD4 Advanced Disease Test in 7 Countries

Tinne Gils  1   2 , Jerry Hella  3 , Bart K M Jacobs  1 , Bianca Sossen  4   5 , Madalo Mukoka  6   7 , Monde Muyoyeta  8 , Elizabeth Nakabugo  9 , Hung Van Nguyen  10 , Sasiwimol Ubolyam  11 , Aurélien Macé  12 , Marcia Vermeulen  5 , Sarah Nyangu  8 , Nsala Sanjase  8 , Mohamed Sasamalo  3 , Huong Thi Dinh  10 , The Anh Ngo  13 , Weerawat Manosuthi  14 , Supunnee Jirajariyavej  15 , Claudia M Denkinger  12   16   17 , Nhung Viet Nguyen  10 , Anchalee Avihingsanon  11 , Lydia Nakiyingi  9 , Rita Székely  12 , Andrew D Kerkhoff  18 , Peter MacPherson  6   19   20 , Graeme Meintjes  4   5 , Klaus Reither  21   22 , Morten Ruhwald  12
Affiliations
Multicenter Study

A Prospective Evaluation of the Diagnostic Accuracy of the Point-of-Care VISITECT CD4 Advanced Disease Test in 7 Countries

Tinne Gils et al. J Infect Dis. .

Abstract

Background: CD4 measurement is pivotal in the management of advanced human immunodeficiency virus (HIV) disease. VISITECT CD4 Advanced Disease (VISITECT; AccuBio, Ltd) is an instrument-free, point-of-care, semiquantitative test allowing visual identification of CD4 ≤ 200 cells/µL or >200 cells/ µL from finger-prick or venous blood.

Methods: As part of a diagnostic accuracy study of FUJIFILM SILVAMP TB LAM, people with HIV ≥18 years old were prospectively recruited in 7 countries from outpatient departments if a tuberculosis symptom was present, and from inpatient departments. Participants provided venous blood for CD4 measurement using flow cytometry (reference standard) and finger-prick blood for VISITECT (index text), performed at point-of-care. Sensitivity, specificity, and positive and negative predictive values of VISITECT to determine CD4 ≤ 200 cells/ µL were evaluated.

Results: Among 1604 participants, the median flow cytometry CD4 was 367 cells/µL (interquartile range, 128-626 cells/µL) and 521 (32.5%) had CD4 ≤ 200 cells/µL. VISITECT sensitivity was 92.7% (483/521; 95% confidence interval [CI], 90.1%-94.7%) and specificity was 61.4% (665/1083; 95% CI, 58.4%-64.3%). For participants with CD4 0-100, 101-200, 201-300, 301-500, and >500 cells/µL, VISITECT misclassified 4.5% (95% CI, 2.5%-7.2%), 12.5 (95% CI, 8.0%-18.2%), 74.1% (95% CI, 67.0%-80.5%), 48.0% (95% CI, 42.5%-53.6%), and 22.6% (95% CI, 19.3%-26.3%), respectively.

Conclusions: VISITECT's sensitivity, but not specificity, met the World Health Organization's minimal sensitivity and specificity threshold of 80% for point-of-care CD4 tests. VISITECT's quality needs to be assessed and its accuracy optimized. VISITECT's utility as CD4 triage test should be investigated. Clinical Trials Registration. NCT04089423.

Keywords: AIDS-related opportunistic infections; CD4 Antigens; HIV; point-of-care; sensitivity and specificity.

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Conflict of interest statement

Potential conflicts of interest. R. S., A. M., C. M. D., and M. R. are or were employed by FIND, the global alliance for diagnostics at the time of the study. FIND is a not-for-profit foundation that supports the evaluation of publicly prioritized tuberculosis assays and the implementation of WHO-approved (guidance and prequalification) assays using donor grants. FIND has product evaluation agreements with several private sector companies that design diagnostics for tuberculosis and other diseases. These agreements strictly define FIND's independence and neutrality with regards to these private sector companies. 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.

Figures

Figure 1.
Figure 1.
Study flow chart. In case of invalid results, the result of the repeated VISITECT was used. Abbreviation: VISITECT, Omega VISITECT CD4 Advanced Disease.
Figure 2.
Figure 2.
Variation in positivity of VISITECT CD4 Advanced Disease by CD4 test result by flow cytometry. The black line represents a generalized additive model of positive VISITECT results (classification as CD4 ≤ 200 cells/µL) as a function of the CD4 on flow cytometry (reference standard), with a 95% CI. This line represents true positivity when reference CD4 ≤ 200 cells/µL and false positivity when reference CD4 > 200 cells/µL. Red and green ticks represent observed results. Under 200 cells/µL, an observed result is either a true positive (100%, above, green) or false negative (0%, below, red) while under 200 cells/µL, an observed result is either a true negative (0%, below, green) or false positive (100%, above, red). Proportions present the observed proportion of correct (in green) and wrong (in red) classification by VISITECT as CD4 ≤ 200 cells/µL or >200 cells/µL, in the following CD4 categories by flow cytometry: 0–100, 101–200, 201–300, 301–500, and >500 cells/µL (empirical data). Abbreviations: CI, confidence interval; GAM, generalized additive model; VISITECT, VISITECT CD4 Advanced Disease.
Figure 3.
Figure 3.
Subgroup analysis for point estimates of sensitivity and specificity of VISITECT CD4 Advanced Disease by CD4 test compared to flow cytometry. The dotted line represents the minimum/acceptable standard for sensitivity and specificity for a point-of-care CD4 test to be used as part of the enhanced care package for advanced HIV disease specified by the World Health Organization [24]. Tanzania was an outpatient-only site, South Africa an inpatient-only site. *Indicates 1-sided CI. Abbreviations: ART, antiretroviral treatment; CI, confidence interval; FN, false negative (CD4 > 200 cells/µL); FP, false positive (CD4 ≤ 200 cells/µL); IQR, interquartile range; TN, true negative (CD4 > 200 cells/µL); TP, true positive (CD4 ≤ 200 cells/µL); VISITECT, VISITECT CD4 Advanced Disease.
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