To the Editors:
We read with interest the article by Larson et al,1 and we would like to summarize findings of point-of-care CD4 testing in a multisite real-world setting at 7 Kampala Capital City Authority health facilities in Uganda under general clinic conditions.
Venous blood samples (n = 225) were run onsite by trained clinic staff using the Pima Analyzer (Alere, Waltham, MA). Excess portions of the same plasma specimen were sent to the Makerere University–Johns Hopkins University laboratory for testing within 24 hours by means of a BD FACSCalibur (BD Biosciences, San Jose, CA) flow cytometer. The Makerere University–Johns Hopkins University laboratory is accredited by the College of American Pathologists and participates in external quality assurance testing. Daily calibrations are performed with commercial controls. The sampled population was 80% female and comprised of HIV-infected persons whose median age was 27 years.
The overall correlation between Pima CD4 and the referent FACSCalibur CD4 results was excellent (Spearman rho = 0.953). However, the correlation strength decreased as patient CD4 counts increased (Figure 1A). Among all paired samples, the Pima Analyzer underreported the CD4 count relative to the FACSCalibur result by a mean of 48 cells/mL [median, −31 CD4 cells/mL; IQR (interquartile ratio), −85 to +6]. One-half (49.8%) of Pima results were within ±50 CD4 cells/mL of the FACSCalibur result. Among FACSCalibur CD4 <350 cells/mL (n = 76), 75% of Pima test results were within ±50 CD4 cells/mL of the FACSCalibur (median difference, −2 CD4 cells/mL; IQR, −31 to +20). Among FACSCalibur CD4 <200 cells/mL (n = 37), 73% and 86.5% of Pima results were within ±25 and ±50 cells/mL of the FACSCalibur, respectively. The median relative difference between the 2 tests was +1 CD4 cells/mL of Pima above FACSCalibur (IQR, −8 to +15). Additionally, the direction of the difference between the 2 tests was inconsistent. Among all paired samples, 30% of Pima results were above the FACSCalibur and 70% were below.
These results reinforce what other research has shown in clinical settings and under research conditions. The Alere Pima Analyzer performs with increasing accuracy as CD4 decreases and is reasonably able to correctly classify patients at clinical thresholds, for example, <350 cells/mL. This research included a small number of patients with CD4 <100 cells (n = 15), which limits our ability to evaluate the accuracy of Pima among severely immunocompromised patients. However, it illustrated 3 points. First, the Pima test performed very well in capturing patients with <100 CD4 cells (100% sensitivity and >99% specificity). Second, two-thirds of patients tested had CD4 >350 cells/mL, which reflects significant usage of Pima in pregnant women. Third, without thoughtful point-of-care integration, the magnitude of point-of-care CD4 testing impact may be quite modest in urban settings with regular access to standard flow cytometry.
Based on its diagnostic performance, Pima is currently not an optimally reliable method for longitudinal monitoring.2,3 Point-of-care CD4 analyzers, including the Pima machine, are however useful in identifying severely immunocompromised patients at high risk of adverse HIV-related clinical events. Furthermore, South African pilot data indicate that point-of-care testing can increase linkages to HIV care, specifically, increased likelihood of completing a secondary referral visit post-CD4 testing.1 Point-of-care CD4 testing may also decrease the time to antiretroviral therapy initiation. More operational research is needed to establish how Pima may be used in a targeted fashion to ensure maximal utility.
Using point-of-care technology at HIV-clinic intake for first-time patients may be 1 effective method of using point-of-care CD4 technology. However, this may present considerable challenges for staff in high-volume clinics. The time to obtain a single Pima CD4 was approximately 20 minutes, resulting in a maximum of 24 sample analyses per machine in an 8-hour workday. Among high patient volume clinics involved in this research, 24 samples would represent only approximately 45% of specimens sent to the referral laboratory daily. During the course of this research, we also observed that higher volume clinics were less likely to use point-of-care CD4 analyzers as part of integrated antiretroviral therapy care, due possibly in part to time constraints of the laboratory staff.
At an operational level, implementation of point-of-care CD4 or any new technology should be done in consultation with clinical staff. Implementation without consultation and training may result in increased burdens on health workers, incomplete understanding of how a new technology can be valuable, and the resulting underutilization of a new technology. Further research on the improvements in patient care by means of point-of-care diagnostics in resource-limited settings will be valuable in building the case for appropriate implementation of this new technology.
1. Larson B, Schnippel K, Ndibongo B, et al.. Rapid point-of-care CD4 testing at mobile HIV testing sites to increase linkage to care: an evaluation of a pilot program in South Africa. J Acquir Immune Defic Syndr. 2012;61:e13–e17.
2. Manabe YC, Wang Y, Elbireer A, et al.. Evaluation of portable point-of-care CD4 counter with high sensitivity for detecting patients eligible for antiretroviral therapy. PLoS One. 2012;7:e34319.
3. Thakar M, Mahajan B, Shaikh N, et al.. Utility of the point of care CD4 analyzer, PIMA, to enumerate CD4 counts in the field settings in India. AIDS Res Ther. 2012;9:26.