A study published in Clinical Infectious Diseases provides evidence that not doing baseline CD4 testing will lead to suboptimal programme outcomes under the ‘Treat All’ strategy. Baseline CD4 testing is critical to identify those with advanced stages of HIV, allowing for timely screening, prophylaxis, and management of life-threatening opportunistic infections.
The Ugandan researchers found that the number of newly diagnosed people having CD4 counts has declined dramatically since the introduction of ‘Treat All’, although routine clinical evaluation has poor diagnostic accuracy: four in five people with a CD4 count below 200 had earlier been assessed as having no symptoms or only mild symptoms.
The study is a grim reminder that without baseline CD4 testing and a full package of HIV care, we will lose out on the potential gains of the ‘Treat All’ approach. By not doing baseline CD4 testing clinicians may not identify people who are in advanced stages of HIV disease and need to be triaged for differentiated management. This may include targeted screening, prophylaxis, and treatment of common opportunistic infections.
Two of the biggest reasons for hospitalisation and death among people living with HIV are TB and cryptococcal meningitis. Those with a CD4 cell count below 200 should get cryptococcal antigen screening, fluconazole for the prevention of cryptococcal meningitis, TB screening using TB-LAM or sputum testing, cotrimoxazole prophylaxis to reduce incidence of PCP (pneumocystis pneumonia) and severe bacterial infection, among other essential lifesaving care elements. A randomised trial has shown a 27% decline in deaths among those with advanced HIV disease who have received elements of this care package.
CD4 testing also helps to monitor immune reconstitution among those who have advanced HIV disease.
This study by Dr Esther Nasuuna and colleagues was conducted in six urban public health facilities in Kampala, Uganda, in 42,672 adults who were initiated on antiretroviral therapy during a six-year period (2013-2018). There were more female participants than male (75% vs 25%), although only 26% of the study participants came from prevention of parent to child transmission of HIV services. The researchers analysed routinely collected data in the electronic medical record system.
The World Health Organization (WHO) guidelines for ‘Treat All’ came out in 2015, yet even in 2013 one in four people were being initiated on antiretroviral therapy without a baseline CD4 count – which was a criterion for initiating treatment at the time. The study shows that baseline CD4 testing declined from 73% to 21% of patients between 2013 and 2018. The decline was the steepest in the first quarter of 2017, soon after the roll out of the ‘Treat All’ strategy in Uganda in December 2016.
The decline of baseline CD4 testing was marginal during the period of 2013-2016 (0.5% fewer people tested per quarter), but it increased rapidly in the first quarter of 2017 (17.8%) and continued through 2018 (3.5% per quarter).
However, routine clinical evaluation of symptoms has poor diagnostic accuracy: 83% of those with advanced HIV disease (CD4 less than 200) and 78% of those with very advanced HIV disease (CD4 less than 100) were earlier assessed as WHO clinical stage one (asymptomatic) or two (mild symptoms).
"Baseline CD4 testing is essential for guiding differentiated care."
Despite the decline in CD4 testing, the number of people with advanced HIV disease has not come down significantly. Among those who had baseline CD4 testing, there was marginal decline during the period 2013-2018 in the number of people with advanced HIV disease (from 29% to 24%) and very advanced HIV disease (from 14% to 12%).
Those who were clinically assessed as being WHO HIV stages three or four (which should have triaged them for more advanced care) had one-third less chance of getting a baseline CD4 test, while those who had presumptive TB had a 29% greater likelihood of having a CD4 test done.
One of the limitations of this study was that it did not explore the reasons for the decline in CD4 testing over the six years, such as healthcare providers’ knowledge of the continued need for baseline CD4 assessment, stockouts of CD4 tests, or machine malfunctioning. Reasons for the decline in CD4 before the launch of ‘Treat All’ will be important lessons for helping to shape HIV programmes.
The WHO guidelines of 2017 recommend a package of screening, prophylaxis, and treatment of opportunistic infections, rapid initiation of antiretroviral therapy, and adherence support for those with advanced HIV disease. “As baseline CD4 testing is essential for guiding differentiated care, our findings suggest a need for routine rapid CD4 assessment, ideally using point-of-care testing, or better algorithms for determining the likelihood of advanced immunodeficiency where rapid CD4 testing is not readily available,” the study authors recommend.
Nasuuna E et al. Reduction in Baseline CD4 Count Testing Following Human Immunodeficiency Virus “Treat All” Adoption in Uganda. Clinical Infectious Diseases, online ahead of print, ciaa261, 5 May 2020.
Ford N et al. The Enduring Burden of Advanced Human Immunodeficiency Virus Disease. Clinical Infectious Diseases, online ahead of print, ciaa265, 5 May 2020 (open access).