Low-level HIV viremia: Definitions, predictors, mechanisms, and clinical outcomes

Key take-home messages

• The definitions of optimal viral suppression, low-level viremia, blips, virologic failure, and recommended management approaches to low-level viremia vary greatly across studies and clinical guidelines.
• There is controversy regarding the clinical implications of persistently low HIV RNA levels that are between the lower limits of detection and <200 copies/mL in patients on antiretroviral therapy (ART). Several studies support the supposition that virologic failure is more likely to occur in patients with viral load (VL) ≥200 copies/mL than in those with low-level viremia between 50 and 199 copies/mL. However, other studies have suggested that detectable viremia at this low level (<200 copies/mL) or even lower (<50 copies/mL) can be predictive of virologic failure and can be associated with the evolution of drug resistance.
• The source(s) and mechanisms of persistent low-level HIV plasma viremia are still largely uncharacterized despite improved detection methods, but evidence suggests that it probably largely arises from clonally expanded CD4+ T-cells, although some contribution of ongoing viral replication cannot be excluded.
• There is a dearth of clinical trials on the management of low-level viremia, and guidelines often reflect expert opinion.
• Low-level- and very-low-level viremia can be the result of multiple factors (including virologic factors, ART adherence, etc). It is often difficult to determine the exact cause or clinical significance. It is possible, though not confirmed, that persistent low-level- and very-low-level viremia may predict higher risk of virologic failure, morbidity and mortality.

• Population(s)
  • General HIV+ population
• Prevention, Engagement and Care Cascade
  • Engagement and Care Cascade
• Engagement and Care Cascade
  • Treatment