Point-of-Care Early Infant Diagnosis of HIV: Moving from Successful Field Evaluations to Routine Use

By Maria Buser, Project Officer, UNITAID Project; Rebecca Bailey, Associate Director, UNITAID Project; Jeff Lemaire, Diagnostics Advisor

Despite decreasing rates of mother-to-child transmission of HIV, each day more than 400 infants are born with HIV and nearly 350 infected children die from AIDS.[1] While coverage of conventional, laboratory-based early infant diagnosis of HIV (EID) has increased in recent years, access to effective testing could be greatly expanded through the integration of point-of-care (POC) testing into national EID networks. POC testing has been shown to significantly increase the proportion of infants who receive their test results, to reduce the turnaround time between sample collection and return of results, and to increase treatment initiation rates[2].

Three instruments have been approved by stringent regulatory authorities (SRA’s) for use in POC EID testing. They are the Alere™q (CE Mark and WHO Prequalified), the Cepheid GeneXpert® (CE Mark and WHO Prequalified), and the DRW Samba I and II (CE Mark). In addition, the EID Consortium recently completed an analysis of pooled data from six countries (Kenya, Malawi, Mozambique, Tanzania, South Africa and Zimbabwe) which demonstrated that the two WHO Prequalified devices, Alere™ q and Cepheid GeneXpert® perform well in the field, when operated by a range of health professionals from nurses and laboratory technicians to medical doctors[3]. The next critical step is to move from successful field evaluations to the effective introduction and routine use of innovative POC technologies in Sub-Saharan Africa.

During an ASLM2016 satellite session, held in Cape Town in December 2016, a panel of speakers presented lesson learned from early programmatic experiences with POC testing. The session highlighted three main factors that contribute to the effective integration of POC technologies into existing laboratory networks: (1) engagement of relevant MOH units and national technical working groups (TWGs); (2) effective site and product selection based on a set of jointly-agreed criteria, and (3) capacity building that includes end-user training for specific POC instruments at site level as well as supervision and monitoring. The session was jointly sponsored by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF), Clinton Health Access Initiative (CHAI), UNICEF and MSF, which are implementing UNITAID-funded POC diagnostics projects.

Engagement of the Ministry of Health (MOH) and national Technical Working Groups (TWGs)

To ensure a smooth and successful integration of POC into diagnostic and clinical services, relevant MOH units and TWGs must be identified and engaged from the onset. Early programmatic experiences have shown that it can be challenging to clearly identify whether the clinical or laboratory units should take the lead within the MOH as point-of-care diagnostics cuts across both laboratory and clinical functions. In some countries, the laboratory TWG has taken the lead, but clinicians have been invited to participate or join the group to ensure that all key stakeholders are involved in the decision making process regarding site and product selection as well as capacity building, both of which are central to the integration of POC into the existing laboratory testing system.

Site and product selection

Strategic- and data- driven site and product selection are key to the effective integration of POC EID into existing laboratory networks. EGPAF has developed an approach that focuses on understanding the context in terms of where POC instruments can be best placed to fill gaps within the conventional laboratory network and, therefore, optimize the use and clinical impact of EID testing. The identification of potential POC EID sites was based on an initial analysis of a number of criteria , including historical site-level data such as testing volume, positivity rates, turnaround time from sample collection to return of results, sample transportation networks, and geographic proximity or referral models to expand the access to EID testing (hub and spoke models). Results of the initial analysis were subsequently discussed with the MOH and relevant implementing partners through technical working group (TWG) forums. A subsequent analysis of the infrastructure and human resource capacity of pre-identified potential sites was performed to ensure successful placement. This analysis also allowed for a better identification of which testing platform is expected to best match the needs and capacity of each specific site. Because each instrument has their own characteristics, performance, capacity, and infrastructure requirements, it is crucial that the right instrument is placed in the right site.  Finally, the analysis of potential POC EID sites, and the most adequate platform for each site, was presented and discussed with the MOH and TWGs for approval and further discussion on timelines for a stepwise enrolment of sites.

EGPAF in Lesotho – an example of the site and product selection approach

In Lesotho, EGPAF collaborated with the MOH and national TWG to identify potential facilities for POC EID placement based on an in-depth analysis of the factors mentioned above. A minimum threshold of 0.5 tests per day was used to ensure operator proficiency and better use of instrument capacity. Additional factors informed site selection such as an existing experience with or use of POC testing, and the availability of pediatric antiretroviral treatment (ART) on site for immediate linkage to care. As a result, out of a pool of potential sites, 66 were excluded for POC EID because they were already adequately served by the conventional EID system or had too little EID volumes to ensure POC testing proficiency. Of the remaining sites, 29 were identified as suitable for PCO EID. Four sites were stand alone, and 24 were hubs that will jointly aim to receive samples from 159 networked spoke sites. In the second step, the most fit for purpose platforms were selected to be placed in those sites based on the service needs identified in those sites. The platforms were selected with respect to key characteristics of the site (e.g. throughput, ease-of-use, maintenance and temperature needs, power requirements, portability, connectivity capabilities, waste management requirements, and price).

Additional site capacity assessments were performed at the selected sites to evaluate and score key capabilities and processes, such as physical infrastructure, including space and electricity; safety procedures; stock management and supply chain issues; pre- and post- testing procedures; data management; and overall capacity to integrate point-of-care testing services for patient care.  Overall results showed that all the facilities were either partially eligible or close to pilot site capacity for POC EID implementation. Assessment results concluded that sites would require some form of physical upgrades and/or process-related improvements prior to implementation. Commonly recommended site-level improvements included the purchase of additional cabinets; improving site-level stock management; and integrating standardized forms to document patient and specimen information.

Figure: Site selection in Lesotho

Capacity building to optimize the full potential of POC in decentralized settings

After selecting sites and products, capacity building efforts should focus on: (1) Training of site-level staff, including end-user training; (2) site supervision support, and (3) remote connectivity that allows for the analysis of error/invalid results for targeted mentoring support.

Malawi – learnings from CD4 point-of-care testing: training, support and documentation

A CHAI/UNICEF pilot study in Malawi on POC CD4 testing showed that end-user training and mentorship are key for a successful introduction and scale up of point-of-care services.

During the pilot study, end-users such as clinicians, nurses or laboratory technicians were trained. The training included intensive practical exercises and reorganization of clinical flow. In each site, a national team provided support during the launch of testing. In addition, teams worked with the manufacturer to fix error and device breakdowns. Supervision visits were carried out once a month for the first two months and then reduced to a bi-monthly rate. Learnings from these trainings and support visits were captured in standard operating procedures (SOPs) and logbooks. In addition, regular data collection provided an overview to ensure the availability and distribution POC CD4 testing commodities. As Malawi is now introducing POC EID, many lessons learnt from the POC CD4 pilot can be applied.

Site supervision support in Lesotho

In Lesotho, EGPAF has tested several site supervision and monitoring approaches such as checklists that cover the entire quality assurance (QA) circle from needs assessment to supervision of usage. In addition, operational evaluations in the form of site visits were performed. They identified that, particularly in the initial pilot phase, site monitoring visits provide essential insights into issues related to human capacity and proficiency, data quality, platform functioning, specimen transport, and performance improvement. Site monitoring visits not only serve the purpose of information gathering and immediate trouble shooting, they also are used to build capacity of health care providers and diagnostic platform operators, and focus on correcting performance gaps in systems and processes.

Multi-country study on connectivity – CHAI’s descriptive study

While POC testing increases access to diagnostic services, due to its decentralized nature, it also creates challenges for monitoring performance. Some platforms have integrated remote connectivity options which support the process.

CHAI showcased that connectivity can facilitate performance monitoring and thus potentially reduce error rates. The study suggests that error rates were around 10% across all countries, that they were consistent across all facility types (lower level facilities will have the same error rates as district hospitals), and that error rates vary across users. Results from the study on connectivity with the Alere Pima POC CD4 machine have shown that the device is able to collect a large amount of data that can be used to address challenges and monitor different levels of the health system in real time. Although the error messages do not differentiate between the causes, the alert helps to remotely identify service and maintenance needs. Based on the experience, consensus was reached that the connectivity feature is a key tool to enhance targeted supervision and mentoring support. Nevertheless, remote connectivity cannot fully replace onsite supervision and mentoring mechanisms.

Key takeaways from the ASLM2016 joint satellite session

Several studies have shown that POC EID testing technology is effective in the field, even when operated by non-laboratory health care workers. Lessons learned from early programmatic experiences can be used to help implementers move beyond successful evaluations to the effective introduction of POC technologies in decentralized settings. These lessons include:

  • Early engagement of relevant MOH units and TWGs: These key stakeholder should be engaged early in decision making related to site and product selection. As POC testing cuts across both diagnostic and clinical domains, it is important to ensure that representatives of both areas are engaged in information sharing and decision making.
  • Site and product selection: A thorough understanding of the EID network context and capacity of potential POC EID sites will inform subsequent product selection.
  • Capacity building: Training of facility staff and instrument end-users is necessary but not sufficient. To build and maintain capacity for POC EID test, close monitoring, supervision and mentoring are needed to optimize the delivery of POC services. Remote connectivity can help gather important data for remote analysis and support to overcome performance challenges.

For more information, please contact Maria Buser.

[1] Children and HIV fact sheet. UNAIDS. July 2016. http://www.unaids.org/sites/default/files/media_asset/FactSheet_Children_en.pdf

[2] Mwenda R. (2016). Impact of point-of-care EID testing into the national EID program: Pilot experiences from Malawi. Presentation at African Society for Laboratory Medicine Early Infant Diagnosis Satellite. 21st International AIDS Conference. July 18-22, 2016. Durban, South Africa.

[3] Carmon S. et al. Field performance of point-of-care HIV testing or early infant diagnosis: Pooled analysis from six countries from the EID Consortium. Poster Presentation, AIDS 2016, Durban, South Africa (www.eidconsortium.org)