Resource-based Approach to Pre-ART CD4 Testing Can Significantly Reduce HIV-related Mortality

Better strategies are needed to adequately identify and prevent opportunistic infections and related deaths in patients with advanced HIV.

Utilizing point-of-care CD4 testing for individuals in low- and middle-income countries could help identify and prevent opportunistic infections (OIs) and related deaths in patients with HIV, according to a new report published in PLOS Medicine.

Rapid initiation of antiretroviral therapy (ART) has been crucial to the progress made in treating HIV; however, a significant proportion of patients starting ART in low- and middle- income countries continue to present with severe immunosuppression. CD4 testing remains the only way to identify those with HIV who are at higher risk of death, with studies having consistently shown CD4 as a key predictor of mortality after ART initiation, according to the authors of the report. Although most HIV high-burden countries recommend baseline CD4 testing, some guidelines state that baseline testing is not required for starting ART.

In the report, the authors indicate that current strategies are inadequate for identifying and preventing OIs and related deaths in these populations. Although prophylaxis against OIs is effective at reducing mortality, the authors noted that these methods cost money and can potentially delay ART initiation when waiting on a diagnostic result, indicating the need for strategies that include point-of-care testing.

The authors suggested that a resource-based approach to implementing pre-ART CD4 testing and other point-of-care tests for OIs in under-resourced centers could significantly reduce HIV-related mortality in these populations. According to the authors, clinical assessments alone are limited in their ability to identify patients with advanced HIV and higher risk of mortality.

“In the REALITY trial, despite a median CD4 of only 37 cells/μL and all participants having advanced HIV with CD4 < 100 cells/μL, only 53% of patients had WHO stage 3 or 4 disease; the other half had few or no discernible clinical symptoms or signs of advanced HIV disease and could not have been identified using clinical criteria alone,” the authors wrote.

The REALITY trial also demonstrated that if the CD4 testing results are <100 cell /μL and no additional OI screening is available, low-dose fluconazole and a 5-day course of azithromycin along with isoniazid/cotrimoxazole/pyridoxine decreased mortality risk by 27%, according to the report.

Still, the challenge is balancing the excess mortality risks associated with potential delays to ART while waiting for test results with the benefits of targeted prophylaxis, the authors noted.

“An optimal approach requires that pre-ART CD4 (preferably as a simple point-of-care threshold test) continues to be available,” they concluded. “We believe this provides a pragmatic algorithm to avoid delaying ART for the most immunosuppressed patients who are at the highest risk of dying.”


Tenforde MW, Walker AS, Gibb DM, et al. Rapid antiretroviral therapy initiation in low- and middle-income countries: A resource-based approach. PLOS Medicine. 2019.

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