‘Treat All’ No Panacea for Early ART Uptake.

Eliminating CD4 treatment thresholds for HIV is unlikely to lead to a critical mass of people living with HIV starting antiretroviral treatment (ART) in South Africa, according to an analysis led by School of Public Health researchers.

A study by Africa Health Research Institute (AHRI) researchers and BU colleagues, published in PLOS ONE, 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 longer and healthier, and reduces the risk of them passing on the virus. Studies have also projected that test-and-treat approaches could reduce HIV transmission and alter the course of the epidemic. In September 2016, South Africa followed World Health Organization 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 analyses of data from 19,279 patients enrolled in a public-sector ART program 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, researchers 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 percent and 26.7 percent, respectively. By scaling the Hlabisa results by the number of ART initiators nationally in 2013 (614,000), the scientists projected increases of 130,000 and 164,000 patients, respectively. These numbers represent increases of 4.3 percent and 5 percent 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, the authors said.

While this will still benefit many thousands of patients, and is therefore of value regardless of other program changes, it is not enough to achieve, on its own, South Africa’s goals, researchers said.

“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 Jacob Bor, assistant professor of global health and 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,” Bor said. “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.”

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 scientific evidence and international guidelines, Bor said.

Co-authors include: Shahira Ahmed, Matthew Fox, Sydney Rosen, Gesine Meyer-Rath, and Ingrid Katz, all from the Department of Global Health; and researchers from the Africa Health Institute and Brigham and Women’s Hospital.