Back to the future with CD4 testing: improving HIV care in low- and middle-income countries

January 15, 2019

A practical resource-based public health approach for the rapid initiation of antiretroviral therapy in HIV-infected individuals living in low- and middle-income countries could save thousands of lives, according to an Essay published January 15 in the open-access journal PLOS Medicine by Mark Tenforde of the University of Washington School of Medicine, and colleagues.

Effective antiretroviral therapy has substantially decreased HIV morbidity and mortality over the past two decades. Several randomized trials have demonstrated benefits from starting antiretroviral therapy regardless of CD4 count, and the World Health Organization adopted a "treat all" strategy in 2015. Significant attention has been focused on rapidly initiating antiretroviral therapy in different settings, and considerable progress has been made. Yet a significant proportion of patients starting antiretroviral therapy in low- and middle-income countries continue to present with severe immunosuppression, with recent laboratory-based surveillance showing that one-third of South African patients enter care with advanced HIV disease. These late presenters have the highest risk for immune reconstitution inflammatory syndrome, unmasking of opportunistic infections including tuberculosis, and death.

According to Tenforde and colleagues, current strategies are inadequate for identifying and preventing opportunistic infections and related deaths in late presenters. The authors present a resource-based approach according to diagnostic test availability for targeting opportunistic infections in the "treat all" era. The approach could decrease early mortality after antiretroviral therapy initiation and would be practical to implement. Even the most resource-constrained settings can implement interventions that have the potential to save thousands of lives, while further refinement can be offered in settings where rapid screening for common opportunistic infections is feasible.

According to the authors, an optimal approach requires that pre-antiretroviral therapy CD4 testing continues to be available (preferably as a simple point-of-care threshold test), although viral load testing has been supplanting CD4 testing in high-burden countries in the "treat all" era. "We believe this provides a pragmatic algorithm to avoid delaying antiretroviral therapy for the most immunosuppressed patients who are at the highest risk of dying," the authors write.
Research Article


The authors received no specific funding for this work.

Competing Interests:

I have read the journal's policy and the authors of this manuscript have the following competing interests: ASW and DMG declare that the REALITY trial which is referred to in this essay and which prompted interest in this area was funded by the Medical Research Council, UK, the Wellcome Trust, and the UK Department for International Development. Drugs were donated from Gilead Sciences, ViiV, Merck, and Cipla Ltd. ASW's institution has received funding for ASW's membership of a DSMB from Janssen and for teaching on courses on critical appraisal and cohort design management and analysis from Gilead Sciences. MWT has received US National Institutes of Health training grant support and has no competing interests to declare. YCM declares US National Institutes of Health and CDC grants to his institution to study point-of-care tests.


Tenforde MW, Walker AS, Gibb DM, Manabe YC (2019) Rapid antiretroviral therapy initiation in low- and middle-income countries: A resource-based approach. PLoS Med 16(1): e1002723.

Image Credit: Snr Airman Austin Harvill, U.S. Air Force

Author Affiliations:

Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America

Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, United States of America

Botswana-UPenn Partnership, Gaborone, Botswana

Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom

Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America

Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda

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