Eliminating CD4 thresholds is unlikely to lead to a critical mass of people living with HIV starting antiretroviral treatment (ART) in South Africa.

A new study by Africa Health Research Institute (AHRI) researchers and Boston University colleagues, published in PLOS ONE in June, shows that ART uptake in rural KwaZulu-Natal (KZN) among treatment-eligible patients is low – and declines at higher CD4 counts.

Clinical trials have confirmed that early use of ART keeps people living with HIV alive, healthier, and reduces the risk of them passing on the virus. Studies have also projected that test-and-treat could reduce HIV transmission and alter the course of the epidemic. In September 2016, South Africa followed World Health Organisation guidelines to “treat all” – removing the CD4 count thresholds which dictated who could receive ART.

However, based on the experiences of patients in rural South Africa, AHRI researchers predict that fewer than one in four newly eligible patients will initiate ART within six months of testing positive. Their results are based on analysis of data from 19 279 patients enrolled in a public-sector ART programme in the Hlabisa sub-district of KZN between August 2011 and December 2013. The researchers used a regression discontinuity design to compare rates of ART uptake in patients presenting with CD4 counts that were eligible versus ineligible for ART – based on a prior threshold. These estimates offer some guidance on the likely impact of eliminating CD4 count thresholds on numbers of new ART initiators – if no other changes are made to HIV testing, linkage to care, or treatment initiation procedures.

In Hlabisa they found that raising the CD4 threshold to 500 and eliminating CD4 criteria entirely were projected to increase the annual number of initiators by 21.2% and 26.7% respectively. By scaling the Hlabisa results by the number of ART initiators nationally in 2013 (614 000), the scientists project increases of 130 000 and 164 000 patients, respectively. These numbers represent increases of 4.3% and 5.2% in the total population of patients receiving ART in South Africa. This pales in comparison to the near doubling of patients on ART required to achieve universal coverage in South Africa. While this will still benefit many thousands of patients, and is therefore of value regardless of other programme changes, it is not enough to achieve, on its own, South Africa’s 90-90-90 targets.

“Our paper identifies substantial attrition between clinical presentation and ART initiation among treatment-eligible patients. It is likely that many of these patients have blood drawn for a CD4 count but never return to the clinic to receive their CD4 results,” said Dr Jacob Bor, a lead author on the paper.  “Changes in testing and initiation procedures – for example, initiating treatment for patients on the same day as diagnosis and other efforts to reduce loss to initiation – as well as interventions to increase demand for early ART are needed. Without these additional improvements to testing and initiation procedures and interventions to increase demand for early ART, eliminating CD4 thresholds is unlikely to achieve the full benefits of treatment as prevention.”

A note on methodology

Treatment thresholds are commonly used not just for HIV, but also in the diagnosis and treatment of diabetes, hypertension, and high cholesterol. They simplify clinical decision-making and align clinical practice with the scientific evidence and international guidelines.  But at what threshold values should patients be offered treatment? This question has been hotly debated for HIV and other conditions as well. The methods presented in this paper show how empirical data can be combined with a simple model to simulate what would happen with thresholds set at different levels. The simplicity of the model and data requirements means that this analysis could easily be implemented for other diseases and contexts, assisting with health systems planning.

Image: Blood is drawn for an HIV test.