CD4 Results with a Bias Larger Than Hundred Cells Per Microliter Can Have a Significant Impact on the Clinical Decision During Treatment Initiation of HIV Patients

Background: CD4 counts are currently used to assess HIV patients for treatment eligibility and to monitor antiretroviral response to treatment. The emerging point-of-care devices could fill an important gap in resource-limited settings. However, the accuracy of CD4-counting instruments is diverse and data on how CD4 measurement errors have an impact on clinical decisions are lacking. Methods: Clinicians were queried on the use of CD4 results in their clinical setting. Subsequently, the effect of CD4 measurement errors on treatment initiation was put in a statistical model. Based on clinical CD4 databases from Belgium, Cambodia, and Senegal, the percentage of unchanged clinical decisions was calculated (treatment initiation should start within a 3-month delay [one visit]) for escalating CD4 measurement errors, taking into account the strict or preventive application of CD4 thresholds at 350 or 500 cells/mu l used by clinicians. Results: To ensure that the treatment was initiated appropriately for at least 95% of patients, an error of 5-10 cells/mu l was allowed. This is significantly smaller than the bias of +/- 50 cells/mu l most clinicians considered acceptable. For limits of agreement (LOA, 1.96 x error) of 100 cells/mu l, corresponding to most CD4 instrument evaluations, the misclassification rate of patients was found to be 3-28% at the threshold of 350 cells/mu l (strict or flexible), and 13220% at 500 cells/ml. Conclusions: The maximum allowed CD4 bias on results from new CD4 technologies should not exceed 50 cells/mu l (LOA 100 cells/mu l) when applied for treatment initiation, to ensure at least 72% of correct clinical decisions. (C) VC 2016 International Clinical Cytometry Society