1. What are CD4 cells?
CD4 cells are a type of white blood cell (also known as CD4 T lymphocytes or “helper T cells”) that help the body fight infection. A higher CD4 count indicates stronger immune system health. CD4 counts decrease over time in people living with HIV (PLHIV) if HIV is not treated with antiretroviral therapy. As the immune system loses CD4 cells, it becomes weaker and is less able to fight off opportunistic infections (OIs).
2. Why is CD4 testing important?
A CD4 test monitors immune system health and disease progression in PLHIV. A healthy person typically has a CD4 count between 500 and 1,500 cells/mm³ (WHO, 2017). When the CD4 count falls below 200 cells/mm³, it indicates advanced HIV disease (AHD), significantly increasing the risk of life-threatening OIs like tuberculosis (TB) and cryptococcal meningitis (CM) (WHO, 2017).
One critical aspect of CD4 testing is its ability to identify AHD in patients who may not exhibit symptoms. The REALITY trial showed that 47 percent of patients with AHD were asymptomatic or mildly symptomatic, despite a very low median CD4 cell count of 37 cells/mm3. Since the World Health Organization (WHO) clinical staging relies on symptom identification, these asymptomatic HIV patients will likely miss a proper diagnosis without a CD4 test (Hakim, J. et al, 2017).
3. What does CD4 testing look like in different settings?
Conventional tests
Most CD4 testing is typically performed in laboratory settings using conventional devices. These machines can process multiple tests simultaneously and are usually stationed in large hospitals, serving as hubs for smaller facilities. Facilities typically must rely on a sample transport network to bring patients’ blood samples to these hospitals for centralized testing. As increasing evidence emerged to support the need for faster linkage to screening and care for AHD patients, efforts have intensified to decentralize CD4 testing and provide timely results.
Point-of-care tests
To address this, point-of-care (POC) devices have been developed for more decentralized settings, requiring minimal electricity and delivering results in about 20 minutes (CHAI, 2023). While POC devices enhance accessibility and reduce the turnaround time, challenges such as initial costs, ongoing maintenance expenses, and the need for reliable electricity affect sustainable implementation in resource-limited areas, where these devices can significantly improve patient care by facilitating prompt CD4 testing and linkage to appropriate treatment.
For the most decentralized settings, where there is no electricity or where conventional and POC devices are unavailable, device-free testing becomes critical. CD4 lateral flow assay (LFA) tests are designed for such environments. These semi-quantitative tests read whether a CD4 cell count is above or below 200 cells/mm³ (CHAI, 2022). Currently, the only available CD4 LFA test is the VISITECT CD4 Advanced Disease test. Although successful use of the LFA test depends heavily on proper training as it involves multiple steps, it does not require costly equipment or maintenance and can be used anywhere, making it ideal for use in remote locations.
4. What are the biggest challenges in the CD4 space?
Low demand
Demand for CD4 tests falls short of the actual need. Despite the critical role of CD4 tests in managing HIV, many individuals who require these tests are not receiving them. The changing indications for CD4 testing, which is not always required to initiate treatment, have led some actors engaged in providing or supporting HIV care to give lower priority to CD4 access. This decrease in perceived value threatens access to timely CD4 testing if CD4 testing networks are not adapted to the needs of AHD screening (WHO, 2020).
Fragmented market
Recent changes to the CD4 market have raised concerns over the supply landscape for CD4 POC testing. In 2022, the manufacturers of both POC devices, Abbott's Pima and BD's FACS Presto, announced that both devices would no longer be available.4 This sudden change has left a gap in the market, complicating efforts to maintain consistent and reliable access to CD4 testing.
Lack of cohesive guidelines
Not all national guidelines on AHD align with the WHO 2017 recommendations (CHAI, 2022). While a CD4 cell count under 200 cells/mm³ is often used for making certain clinical decisions, such as the initiation of screening for OIs like TB, some countries do not recommend a comprehensive package of care until the cell count falls below 100 cells/mm³. This discrepancy underscores the need for standardized guidelines, especially in areas where quantitative tests may not be available.
5. What’s next for CD4 testing?
Addressing the current challenges in the CD4 landscape demands a coordinated effort at the regional, national, and global levels. CHAI and other stakeholders are engaging with suppliers to find ways to increase uptake of existing technologies, while also calling for expression of interest from manufacturers who are interested in supporting solutions to increase access to CD4 testing. Additionally, countries need updated CD4 guidelines that can potentially simplify clinical decision-making for PLHIV who require CD4 testing to be linked to screening for OIs.
The reprioritization of CD4 testing by donors, governments, and other stakeholders will create a more equitable healthcare landscape so that PLHIV in all settings have the optimal diagnostic required by the AHD package of care. By ensuring CD4 testing remains accessible, we can facilitate timely, equitable, and lifesaving testing and treatment for those who need it the most.
For more detailed information about CD4, consider exploring the following resources:
WHO 2017 Guidelines: This document provides an in-depth look at the essential components needed for the care of individuals with AHD, including CD4 testing.
Target Product Profile: Learn about the ideal features and functionalities of POC CD4 testing, which can improve accessibility and convenience in various healthcare settings.
Viral Load and CD4 Testing: Understand the importance of regular CD4 testing in monitoring and managing the health of individuals undergoing ARV.
The Global AHD Toolkit: This toolkit offers extensive resources and guidelines on managing AHD, including the integration of CD4 testing into the overall care package.