The Perils of Overly Sensitive Viral Load Testing for Persons With Human Immunodeficiency Virus

Abstract

The concept of undetectable = untransmittable (“U = U”) has been revolutionary both in the prevention and treatment of persons living with HIV. Most studies proving the concept of U = U used an HIV viral load cutoff of 200 copies/mL to define being undetectable. Since then, increasingly sensitive commercial viral load assays, sometimes down to a lower limit of detection (LLD) of 20 copies/mL, lead to confusion about the definition of undetectable and when someone is truly considered untransmittable. Viral loads between the LLD and 200 copies/mL have been associated with future virologic failure; however, no data exist to suggest that intervening in those patients leads to any meaningful benefits. In the absence of a demonstrable benefits of reporting such low viral loads, we view this practice as harmful. We suggest recommendations for adjusting viral load reporting, improving provider counseling, and call for research designs to mitigate the harms of overly-sensitive viral load testing.

How low should we go? Potential and challenges of ultrasensitive CMV assays and solid organ transplantation

“…In a study where they lowered the initial threshold for treatment of D + R, they saw higher rates of recurrent infection necessitating treatment, suggesting a need for antigenic exposure to mitigate the risk of further infection. 9 With human immunodeficiency virus (HIV), viral loads between 200 copies/mL and the lower limit of detection have been associated with future virologic failure, although no data suggest that intervention leads to any meaningful benefits, and in the absence of any demonstrable benefits, some authors postulate that reporting of such low viral loads may be harmful 10 ; the same could be true for CMV. As we improve CMV qNAT diagnostics, we need further clarity on best practices in this vulnerable population.…”