Head to head comparisons in performance of CD4 point-of-care assays: a Bayesian meta-analysis (2000–2013)

Abstract

Timely detection, staging, and treatment initiation are pertinent to controlling HIV infection. CD4+ cell-based point-of-care (POC) devices offer the potential to rapidly stage patients, and decide on initiating treatment, but a comparative evaluation of their performance has not yet been performed. With this in mind, we conducted a systematic review and metaanalyses. For the period January 2000 to April 2014, 19 databases were systematically searched, 6619 citations retrieved, and 25 articles selected. Diagnostic performance was compared across devices (i.e., PIMA, CyFlow, miniPOC, MBioCD4 System) and across specimens (i.e., capillary blood vs. venous blood). A Bayesian approach was used to meta-analyze the data. The primary outcome, the Bland–Altman (BA) mean bias (which represents agreement between cell counts from POC device and flow cytometry), was analyzed with a Bayesian hierarchical normal model. We performed a headto-head comparison of two POC devices such as PIMA and PointCareNOW CD4. PIMA appears to perform better vs. PointCareNOW with venous samples (BA mean bias: –9.5 cells/μL; 95% CrI: –37.71 to 18.27, vs. 139.3 cells/μL; 95% CrI: –0.85 to 267.4, mean difference = 148.8, 95% CrI: 11.8, 285.8); however, PIMA’s best performed when used with capillary samples (BA mean bias: 2.2 cells/μL; 95% CrI: – 19.32 to 23.6). Sufficient data were available to allow pooling of sensitivity and specificity data only at the 350 cells/μL cutoff. For PIMA device sensitivity 91.6 (84.7–95.5) and specificity was 94.8 (90.1–97.3), respectively. There were not sufficient data to allow comparisons between any other devices. PIMA device was comparable to flow cytometry. The estimated differences between the CD4+ cell counts of the device and the reference was small and best estimated in capillary blood specimens. As the evidence stands, the PointCareNOW device will need to improve prior to widespread use and more data on MBio and MiniPOC are needed. Findings inform implementation of PIMA and improvements in other CD4 POC device prior to recommending widespread use. INTRODUCTION Universal access to antiretroviral therapy (ART) and increased levels of HIV testing have created hope that HIV infection can be controlled globally. Approximately 9.7 mil‐ lion people now receive ART in lowand middle-income countries, representing a 32-fold increase over the last decade [1]. Effective ART reduces viral load (VL) to undetectable levels and dramatically reduces associated mortality and morbidity [2–4]. As a public health intervention, ART is at the core of a treatment-as-prevention strategy, as reducing community viral load reduces HIV transmissions [4]. CD4+ cells counts and measures of VL are surrogate biomarkers of disease progression that help to stage, initiate and monitor treatment. CD4+ cell counts provide an immunological measure of HIV progression; these counts are utilized in the care of HIV+ patients for staging infections and in assessing patients for ART eligibility [5–8]. Specialized laboratories use highly trained personnel and sophisticated flow cytometry techniques to perform CD4+ cell counts, as this is the current gold standard technique [6, 9]. When ART is available, rapid staging, continual monitoring, and retention of individuals on ART become crucial to controlling HIV infection, but the availability of quality patient monitoring in all field settings remains a challenge [10]. SOR-MED