Introduction.

The HIV epidemic remains a major global public health challenge with an estimated 34 million people living with HIV worldwide [1]. The past decade has witnessed a remarkable global effort to improve access to HIV antiretroviral therapy (ART). Despite the progress, approximately half of all people who need treatment do not yet receive it.

Enumeration of CD4 lymphocytes is an essential diagnostic tool for initiating therapy and monitoring its efficacy [2]. CD4 testing typically relies on complex flow cytometry equipment which requires infrastructure and technical skills which are commonly unavailable at rural and remote clinics [3].

New point-of-care (POC) CD4 technologies enable testing to be decentralized to these sites and for test results to be provided during the course of the patient visit. Recent studies have demonstrated that POC CD4 can significantly improve rates of ART initiation and reduce patient loss-to-follow-up, which is often high before treatment initiation. Immediate access to CD4 results may also enable more rapid initiation of prophylactic treatment for opportunistic infections as well as chemotherapy for prevention of mother-to-child transmission at sites where CD4 levels define the prophylactic drug regimen [4], [5]. Expansion of POC CD4 testing is therefore a priority initiative to improve access to treatment for HIV and AIDS, and several POC CD4 technologies have recently become available, or are expected in the near future [6]–[8]. As these are new technologies with limited track record, rigorous independent assessment of their performance is required so that public health managers can make informed decisions around technology selection and deployment. International prequalification systems for such diagnostic devices are being developed [9].

Introduced in 2008, the PointCare NOW technology (PointCare, Marlborough, MA, USA), was designed for HIV/AIDS patient care in resource-limited settings. This fully automated platform provides absolute CD4 count, CD4% and hematology parameters. To date, no independent evaluation on the performance of PointCare NOW system has been published. This report summarizes results from five independent studies conducted in Southern Africa and North America on the performance of PointCare NOW system for CD4 counting.

Abstract.
Introduction.

Point-of-care (POC) CD4 testing can improve access to treatment by enabling decentralization and reducing patient loss-to-follow-up. As new POC CD4 technologies become available, their performance should be assessed before widespread deployment. This study reports the findings of five independent evaluations of the PointCare NOW CD4 system.

Materials/Methods.

Evaluations were conducted in Southern Africa (Mozambique, South Africa) and North America (Canada, USA). 492 blood samples (55 from HIV-negative blood donors and 437 from HIV-infected patients, including 20 children aged between 12 and 59 months) were tested with both the PointCare NOW and reference flow cytometry instruments. Assessment of bias, precision and levels of clinical misclassification for absolute and percent CD4 count was conducted.

Results.

PointCare NOW significantly overestimated CD4 absolute counts with a mean relative bias of +35.0%. Bias was greater in samples with CD4 counts below ≤350cells/µl (+51.3%) than in the CD4 >350cells/µl stratum (15.1%). Bias in CD4% had a similar trend with an overall relative mean bias of +25.6% and a larger bias for low CD4 stratum (+40.2%) than the higher CD4 stratum (+5.8%). Relative bias for CD4% in children was −6.8%. In terms of repeatability, PointCare NOW had a coefficient of variation of 11%. Using a threshold of 350cells/µl, only 47% of patients who qualified for antiretroviral therapy with reference CD4 testing, would have been eligible for treatment with PointCare NOW test results. This was 39% using a 200cells/µl threshold. Agreement with infant samples was higher, with 90% qualifying at a 25% eligibility threshold.

Conclusion.

The performance of the PointCare NOW instrument for absolute and percent CD4 enumeration was inadequate for HIV clinical management in adults. In children, the small sample size was not large enough to draw a conclusion. This study also highlights the importance of independent evaluation of new diagnostic technology platforms before deployment.