Defining treatment failure in resource-rich settings

To define treatment failure in resource-rich settings; summarizing current guidelines, assays, the significance of detectable viremia, and definitions of treatment failure in clinical and research settings.

The goal of treatment should be full viral suppression, even in highly treatment-experienced patients.

Treatment failure is defined as repeated HIV RNA values above the lower limit of detection of a sensitive assay (usually 50 copies/ml). This criterion is based on evidence that the maximum clinical benefit of antiretroviral therapy is derived by keeping the viral load as low as possible. Full viral suppression should be achievable in all patients, both treatment-naïve and experienced. Transient, low-detectable viremia ('blips') may not predict virologic breakthrough. However, consecutive or higher-level transient viremia is associated with risk of treatment failure. Defining failure by a confirmed HIV RNA more than 50 copies/ml is the most conservative approach, but the use of such low limits of detection in clinical trials may lead to a high false-positive 'failure' rate, thus a definition of 200 copies/ml may be preferable. Variation in clinical trial endpoint definitions creates a challenge for comparing results between studies. For example, using a composite endpoint to define treatment failure may result in a high proportion of 'failures' that are not related to poor virologic response.