When Clinical Algorithms Outpace the Markets That Serve Them : The CD4 Comeback Story Nobody Planned For

A decade ago, a shift in the clinical guidance convinced an entire market that CD4 testing was fading out. The guidance has since changed and reaffirmed the importance of CD4 testing, but getting the market to come back to life is proving to be much harder.

The machine sits on a shelf in the corner of the clinic, unplugged. Nobody remembers exactly when it stopped working; the reagents ran out sometime last year, the distributor never restocked them, and eventually someone unplugged the machine and moved it into a corner of the clinic, where it would not be in the way. It's a point-of-care CD4 analyser, designed to give a real time assessment when health workers need to assess how much of an HIV patient's immune system is left.

Months after the CD4 machine was set aside to gather dust, a woman walks into a health facility that is 2 hours from the nearest paved road; the nearest functioning lab is half a day’s journey. She started HIV treatment two years ago, but she stopped when she moved to a different town to care of her mother, and has just come back.  

The point of care CD4 analyser was primarily positioned for a scenario such as this;someone re-entering care, possibly with a badly damaged immune system, and at risk of dying from something that a healthy person would shrug off. Unfortunately, the nurse does not have a working CD4 test. Instead, she has a referral slip and a four-hour trip to the nearest lab that can do this kind of test.

How did that CD4 machine end up unplugged? And why, a year after the World Health Organization re-affirmed CD4 as the preferred way to identify advanced HIV disease,  is it  still sitting there gathering dust?

A test that was the star of the show

CD4 testing was not always a footnote. For the first two decades of the HIV response, it was the test that was central to HIV treatment decisions. The CD4 result determined whether you started antiretroviral therapy, and later, whether that therapy was working.

Then the evidence shifted. In 2015, WHO recommended that everyone living with HIV start treatment immediately, regardless of their CD4 count; trials had shown that waiting for the immune system to decline before treating someone was costing lives.  

Moreover, the change in the WHO guidelines also did something nobody quite reckoned with at the time - it took away CD4's biggest job overnight. The threshold that had previously triggered millions of tests a year no longer existed. Viral load testing took over as the tool of choice for monitoring people already on treatment, and donor funding followed in that direction.  

It was not wrong to prioritise viral load. Unlike the CD4, viral load is an important signal that tells us whether the virus itself is under control. But what CD4 does tell us is how vulnerable someone's immune system still is, especially when it's badly weakened by an untreated HIV infection or other chronic infections.  

To be fair, WHO guidelines did not say that one test mattered more than another.  They just redefined CD4 to be used to identify advanced HIV disease, trigger extra care, and to guide who needs preventative drugs against specific infection that target people with weak immune systems, such as TB.  However, the investment and the market followed the volumes, and the testing volumes were now coming from viral load monitoring.  

What happens to a market when the funding goes away

We need to recognize that manufacturers watch demand signals, not clinical nuance. When donor money shifted to viral load, CD4 testing volumes fell for a decade, and the companies making CD4 diagnostics did what any company does when a market shrinks - they left. Point-of-care platforms, the devices designed for clinics like the one in this story, without a lab down the hall, were hit the hardest. The Global Fund now describes the point-of-care CD4 market as one "in transition," a polite way of saying that one major platform is gone entirely and another has shifted production to an on-demand basis.

A shrinking market and a shrinking clinical need are not the same thing, and it is easy to mistake one for the other. Some diagnostics move from mass routine use into a smaller, but higher-stakes niche. When that happens, all the usual signals that a market typically looks for - falling volume, or thinning supplier interest – suggest a decline. However, what looks like a waning market, in this case, is actually a test that has become more important to sicker, albeit fewer people.

The people now needing CD4 were not the newly diagnosed majority who start treatment early and do well. They were the harder cases; people who are seriously ill and re-engaging in care like the woman in our clinic, or people whose treatment has failed. Roughly 570,000 people still die of AIDS-related illness every year, most of them from advanced disease that a CD4 test would have caught.

The need for the test did not disappear; the market just stopped seeing it.

The comeback

In December 2025, WHO made the correction official: CD4 testing was highlighted as the preferred method for identifying advanced HIV disease. It was an admission of sorts; we had allowed a critical tool in the HIV response to fall by the wayside, while everyone's attention was elsewhere.

A guideline change is the stroke of a pen, and can be changed overnight. However, markets are the result of a decade of decisions, and cannot change overnight. A functioning market is a complex interplay of instruments, trained staff, reagent supply chains, and manufacturers who believe there's a business worth staying in. None of that falls back into place simply because WHO published an update. Six months after the new guidance, a market analysis across six countries found that CD4 testing volumes had fallen another 35% compared to the year before - roughly 236,000 fewer tests, and getting worse in most countries studied. The clinical world moved but the market has not caught up. The nurse in our clinic is still filling out that referral slip.

Four questions for how we move forward

At Market Access Africa, as we work alongside health providers, laboratories and supply chains, we are seeing the same pattern play out, not just in HIV, but across the diagnostic markets.  

The story is bigger than just CD4, and it begs the following questions.  

1. Should major guideline transitions include a market-impact assessment?

In the same way that clinical guidelines must follow the evidence, recommendations affecting diagnostic utilization also generate market signals which should be considered.  

Before a major use case is reduced or removed, it is valuable to assess the implications of the changes to the supplier base, installed equipment, service networks, procurement volumes and residual clinical demand, to enable distinguishing of obsolete diagnostics versus a tool whose use case is changing. This difference has consequences for market stewardship. To be sure, the clinical case is the leading decision factor, but market impact to prepare programmes and manufacturers, should also be taken into account. In the case of CD4, market impact assessments were actually carried out, and recommendations made however, the market actors did not sufficiently act to preserve some baseline capacity as funding shifts and reduced orders erased much of the market.

2. What is the minimum viable market for an essential diagnostic?

Markets work well when volumes are large and predictable. They become harder to sustain when demand is smaller, and concentrated among clinically vulnerable populations. If a test remains essential for a defined population, relying on conventional commercial incentives alone may not preserve adequate supply.

A minimum viable market may require better forecasting, coordinated procurement, demand aggregation, longer purchasing commitments, supplier diversification or other mechanisms that reduce uncertainty for both programmes and manufacturers.

3. Should transition planning preserve capability before it is needed again?

Diagnostic capacity is easier to maintain than to reconstruct. When testing volumes fall, instruments age, service agreements lapse, trained staff move on and supply chains become thinner, suppliers exit the market and reversing those decisions may require new product development, regulatory work, manufacturing investment, procurement qualification and country-level introduction.

Transition plans should therefore identify the level of capacity that should be maintained for residual but important clinical indications. This is particularly relevant in donor-influenced markets, where funding changes can amplify the commercial signal created by new guidance. ‍

4. Can we design the CD4 market around its current clinical purpose?

Rebuilding access does not mean that we have to recreate the CD4 market of 2015 when the global demand for CD4 was 18 million tests, compared to 2025 at 7.6 million CD4 tests. It requires designing a market suited to the CD4 use case of today.

WHO's 2025 implementation guidance already points toward this more differentiated approach. Conventional CD4 testing remains suited to higher-volume facilities with laboratory infrastructure. Point-of-care approaches can support rapid result return and decentralized testing, including outreach settings. WHO also emphasizes task sharing, quality assurance, clear referral pathways and optimization of diagnostic networks so that technologies are matched appropriately to facility needs.

The market-access challenge is to translate that clinical architecture into sustainable demand. That means understanding where patients requiring CD4 testing enter or re-enter the health system, estimating testing volumes at each level, selecting appropriate technologies, maintaining viable procurement volumes, ensuring that a positive AHD identification leads immediately to the rest of the recommended care pathway, and keeping manufacturers engaged throughout the journey.

This is not just a story about CD4. Every guideline that is updated leaves a market somewhere that hasn't caught up. Markets don't collapse all at once. They erode quietly, one unexamined assumption at a time, while the world's attention moves on to the next priority. Let’s not wait another decade to notice, and let’s rather support guideline changes at a market level too.

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Written by: Nancy Njoku-Attah - Manager, Commercial Life Sciences.