Overcoming obstacles to diagnosing and treating advanced HIV disease

Despite significant progress in the fight against HIV, approximately one-third of all people living with HIV only present to care by the time the virus has severely weakened their immune systems and they are at an advanced stage of the disease.

The amount of CD4 cells, a subset of white blood cells, provides an indication of the health of the immune system, and as such, CD4 cell count testing is a vital tool that can be used to help decrease the number of people dying from HIV/AIDS.

In its latest guidelines for managing advanced HIV disease, or AHD, the World Health Organization notes, “CD4 cell count testing at baseline for all people living with HIV remains important,” adding that “relying on clinical staging alone risks missing substantial numbers of people living with HIV with severe immune suppression.”

CD4 cell count tests are also useful to help diagnose patients who may have health systems compromised by opportunistic infections related to AHD, such as cryptococcal disease and tuberculosis, and — according to WHO — can foster a “shift away from symptom-based tuberculosis screening toward an approach of testing all those at high risk of disease.”

In a recent Devex survey, health care professionals agreed that CD4 cell count testing — which is recommended in the WHO “package of care” — is necessary, citing insufficient CD4 testing as one of the reasons for the entrenchment of AHD in low- and lower-middle-income countries.

The survey, conducted from Nov. 16 to Dec. 11, 2020, interviewed more than 700 global health professionals based in 90 countries. The objective was to identify barriers and opportunities around the use of CD4 cell count testing as part of the efforts to reduce AIDS-related deaths.

Overall, building the capacity of health care personnel in identifying and handling AHD cases was considered the most important factor in addressing AHD, at 59%, followed by intensified support interventions for patient adherence to antiretroviral therapy, at 52%. Expanding access to diagnostic tools and services ranked third, at 45%, tied with government policy for AHD.

A quarter of respondents attributed the persistently high levels of AHD to weak and poorly targeted AHD interventions, while 18% mentioned low access to and capacity for diagnosis and monitoring. “[There is] poor access and lack of global support for CD4 testing, which is the gateway to the AHD package of care, as well as a lack of focus on, and clear guidance from, governments,” said a respondent from Zimbabwe.

Now, the COVID-19 pandemic could further exacerbate the situation. A majority — 90% — of professionals said they expected AHD numbers to surge, with 42% citing limited access to health care facilities, commodities, and services as major factors.

A little over half of respondents said AHD is typically diagnosed through CD4 cell count testing and clinical staging as indicated by viral load, although results varied across regions and income levels.

Among the suggestions to improve the implementation of WHO guidelines, respondents mentioned building diagnostic capacity, including with equipment and services, and creating demand among patients and health care workers.

“The lack of funding for infrastructure and capacity building of health care providers is one of the reasons to reach out to all people living with HIV,” said a respondent from India. But the “CD4 machine needs to be…in all primary health centers to increase access,” the respondent added.

“[Uganda] complies with treatment support guidelines offered by WHO. Without knowing the CD4 cell count, prescribing the right regimen and drug combinations becomes difficult for healthcare service providers,” said a survey participant from Uganda.

Health care workers considered CD4 testing crucial for the management of HIV but said it is insufficiently implemented. While most respondents — 91% — agreed that people who test positive for HIV should undergo such testing, only 55% said health care practitioners in their countries typically recommend it to people who are newly diagnosed with HIV.

Overall, they cited limited CD4 testing equipment, limited public access to CD4 testing, and a lack of domestic funding as the top barriers to implementation in their countries.

Other reasons that clinicians fail to recommend CD4 testing include a lack of well-maintained machines and an insufficient supply of reagents due to a lack of funding.

“Clinical staging is typically used to diagnose AHD, which can still be improved. We don't have enough point-of-care CD4 machines, so laboratory results take a long time to come back,” said a respondent from Zambia.

Meanwhile, a health care worker from the Democratic Republic of Congo said:

“The gold standards are clinical staging and CD4 testing. Unfortunately, the reagents are not always available.”

The unavailability of reagents is likely due to lack of funding. The Clinton Health Access Initiative, in its 2019 “HIV Market Report,” suggested that "although there is sufficient aggregate CD4 testing capacity in many countries to meet all of the AHD screening need, access to onsite POC [point-of-care] CD4 testing varies by country and a lack of funding for reagents and programmatic support remain the key barriers to meeting this need."

Yet another factor is the current emphasis on scaling up viral load testing for treatment monitoring. According to a survey respondent from Kenya, “more support is required for CD4 testing as a lot of focus is currently on viral load testing.”

Donor funding has shifted away from CD4 testing and toward viral load testing, 49% of respondents agreed, while only 17% said it has not. In addition, 45% said there is not enough domestic funding for CD4 testing in their countries.

“CD4 testing is domestically funded, which is becoming less and less affordable,” noted a respondent from South Africa. A respondent from Nigeria said: “There is not enough funding for CD4 testing because it is donor-driven. The government needs to have a policy that would allocate the costs of CD4 testing into the budget for sustainability.”

To best take advantage of existing CD4 testing equipment in their respective countries, respondents suggested investing in repair and maintenance, at 39%; training personnel on the use of CD4 machines, at 19%; and ensuring that policies support CD4 testing, at 18%.

“Refurbish or service the machines and place them at district hospitals in districts that are failing to meet the global targets on HIV treatment,” suggested a respondent from Zimbabwe. “There is a need to revitalize the existing platforms and begin testing CD4 along with viral load,” said another respondent from Zimbabwe.

Equipment for CD4 cell count tests remains limited and lacks funding, but there are opportunities to improve and optimize current investments. Newer, more portable, and more user-friendly CD4 testing machines, for example, could make it easier for health workers to maintain the equipment. If something breaks down, it can easily be replaced by another module.

While barriers to greater uptake exist, health care professionals agreed that CD4 cell count testing is essential for properly diagnosing AHD, as part of a range of interventions such as more training of health care workers, conducive government policies, more funding, and access to CD4 testing equipment.