Virologic failure following persistent low-level viremia in a cohort of HIV-positive patients: results from 12 years of observation

Abstract

Background: The current goal of antiretroviral therapy (ART) is to maintain a suppressed human immunodeficiency virus (HIV) viral load below limits of assay detection. When viral loads remain in low-level viremia (LLV), especially between 50 and 200 copies/mL, the best management and clinical consequences remain unknown. Our objective was to study the long-term impact of persistent LLV on the subsequent risk of virologic failure in a cohort of people living with HIV in Montreal, Canada.

Methods: We compared the cumulative incidence of subsequent virologic failure (defined as an HIV RNA viral load of >1000 copies/mL) in patients receiving ART for at least 12 months by following 4 persistence categories (<50, 50-199, 200-499, and 500-999 copies/mL) for 6, 9, or 12 months, using Kaplan-Meier analysis. The association between subsequent virologic failure and persistence status were estimated using a Cox proportional hazards model.

Results: The cumulative incidence of virologic failure 1 year after having maintained a LLV for 6 months was 22.7% (95% confidence interval [CI], 14.9-33.6) for 50-199 copies/mL, 24.2% (95% CI, 14.5-38.6) for 200-499 copies/mL, and 58.9% (95% CI, 43.1-75.2) for 500-999 copies/mL, compared with 6.6% (95% CI, 5.3-8.2) for an undetectable HIV RNA viral load. Even after adjustment for potential confounders, a persistent LLV of 50-199 copies/mL for 6 months doubled the risk of virologic failure (hazard ratio, 2.22; 95% CI, 1.60-3.09), compared with undetectable viral loads for the same duration. Similar results have been found for persistent LLV of 9 or 12 months.

Conclusions: In this cohort, all categories of persistent LLV between 50 and 999 copies/mL were associated with an increased risk of virologic failure. The results shed new light for the management of patients with LLV, especially with regard to LLV of 50-199 copies/mL.

Keywords: HIV; cohort study; low-level viremia; viral load; virological failure.