Virological Failure Definition
Virological failure is defined as a confirmed plasma HIV RNA level above 200 copies/mL on two consecutive measurements in an individual receiving antiretroviral therapy. 1
Threshold Clarification
The International Antiviral Society-USA (IAS-USA) guidelines consistently define virological failure as confirmed HIV RNA >200 copies/mL, not 1000 copies/mL, across their 2016 and 2020 recommendations published in JAMA. 1
The 200 copies/mL threshold requires confirmation with a repeat measurement within 4 weeks to exclude laboratory error or transient elevation. 1
The 1000 copies/mL threshold is used in WHO guidelines for resource-limited settings but is not the standard for resource-rich settings where more sensitive monitoring is feasible. 2
Distinction from Viral Blips
A virological blip is defined as an isolated increase in HIV RNA to <1000 copies/mL with subsequent return to undetectable levels, and this is not considered virological failure. 1, 3
Switching ART based on a single blip is not recommended, as blips rarely progress to true virological failure. 1, 3
Low-Level Viremia (50-200 copies/mL)
HIV RNA persistently between 50-200 copies/mL represents a gray zone where data are inconsistent regarding long-term outcomes. 1
Patients with persistent viremia in this range should be reassessed for adherence issues, drug interactions, and monitored closely with repeat testing within 4 weeks. 1, 4
Research evidence suggests that persistent low-level viremia between 50-199 copies/mL doubles the risk of subsequent virological failure compared to undetectable levels, though this does not meet the formal definition of failure. 5, 6
Clinical Action Thresholds
Treatment should be changed in patients with persistent HIV RNA above 200 copies/mL after confirmation. 1
Genotypic resistance testing should be performed at the time of confirmed virological failure, though amplification may not be successful below 500-1000 copies/mL. 1
If HIV RNA remains above the limit of quantification by 24 weeks after ART initiation, or if rebound above 50 copies/mL occurs at any time during treatment, repeat testing within 4 weeks is required to assess for impending virological failure. 1
Common Pitfalls
Do not confuse a single detectable viral load with virological failure—confirmation is required. 1
Do not switch therapy based on isolated blips <1000 copies/mL that return to undetectable levels. 1, 3
Do not order resistance testing for viral loads <200 copies/mL, as the test is unlikely to amplify successfully and does not meet the threshold for confirmed failure. 1, 4