Durable HIV Treatment Benefit Despite Low-Level Viremia: Reassessing Definitions of Success or Failure

Left untreated, human immunodeficiency virus (HIV) replicates at a rapid rate, with the eventual production of billions of new virus particles per day. Given the propensity of HIV to mutate, the possibility exists that each newly produced virus contains at least 1 new mutation. Thus, from a darwinian perspective, ongoing viral replication in the presence of therapy should result in the rapid selection of drug resistance mutations and subsequent virologic rebound. These basic principles have provided the theoretical context for the "hit hard" therapeutic approach to HIV disease.¹ According to current treatment guidelines,^1-3 complete viral suppression should be the goal of therapy. Once therapy is initiated, plasma viremia, as measured by the concentration of viral RNA in plasma, should decrease to below the level of detection using the most sensitive assay available.^2,3 Persistent viremia suggests ongoing viral replication and treatment failure. The findings from 2 articles in this issue of THE JOURNAL raise questions about this conceptual framework, and based on data from the 2 studies, it may be argued that "complete" viral suppression may not be a prerequisite for durable treatment benefit.