Low-level viremia in HIV-1 infection: consequences and implications for switching to a new regimen

Virologic failure, or the inability to maintain or achieve viral suppression below detectable limits (<50 copies/mL), occurs in some patients with human immunodeficiency virus (HIV)-1 infection, despite being on a potent antiretroviral (ARV) regimen. Current guidelines state that the goal of therapy is to achieve and maintain HIV-1 RNA below detectable levels, with recommendations to switch regimens upon virologic failure based on the adverse consequences of higher degrees of viremia. With the introduction of potent, newer agents, the likelihood of achieving this goal in treatment-experienced patients is growing. Not all patients who experience virologic failure while on therapy suffer from immediate virologic and immunologic decline; some experience persistently low, but detectable, levels of HIV-1 RNA in the range of 50-1000 copies/mL. The threshold at which low-level viremia (LLV) becomes predictive of disease progression varies between studies, although evidence shows that incomplete viral suppression leads to the accumulation of resistance mutations with a concomitant increase in viral replication, reduction in CD4 cell counts, increased risk of virologic progression, and clinical deterioration. Furthermore, with increasing resistance, future treatment options are compromised. Although there are clinical consequences when a patient is maintained on a failing regimen, it may be preferable to delay a switch in therapy if the chance for resuppression is low. With the introduction of new ARVs within existing classes that have shown significant activity against resistant virus, as well as the introduction of two new classes of ARV agents, HIV treatment has entered a new era. The options for constructing regimens active against multidrug-resistant virus have expanded.