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Urgent need to improve programmatic management of patients with HIV failing first-line antiretroviral therapy.

Introduction
Delayed identification and response to virologic failure in case of first-line antiretroviral therapy (ART) in resource-limited settings is a threat to the health of HIV-infected patients. There is a need for the implementation of an effective, standardized response pathway in the public sector.


Discussion
We evaluated published cohorts describing virologic failure on first-line ART. We focused on gaps in the detection and management of treatment failure, and posited ways to close these gaps, keeping in mind scalability and standardization. Specific shortcomings repeatedly recorded included early loss to follow-up (>20%) after recognized first-line ART virologic failure; frequent delays in confirmatory viral load testing; and excessive time between the confirmation of first-line ART failure and initiation of second-line ART, which exceeded 1 year in some cases. Strategies emphasizing patient tracing, resistance testing, drug concentration monitoring, adherence interventions, and streamlined response pathways for those failing therapy are further discussed.


Conclusion
Comprehensive, evidence-based, clinical operational plans must be devised based on findings from existing research and further tested through implementation science research. Until this standard of evidence is available and implemented, high rates of losses from delays in appropriate switch to second-line ART will remain unacceptably common and a threat to the success of global HIV treatment programs.