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

Area of Science:

• Virology
• Public Health
• Infectious Diseases

Background:

• The "undetectable = untransmittable" (U = U) concept revolutionized HIV prevention and treatment.
• Historically, an HIV RNA viral load (VL) below 200 copies/mL defined undetectability for U = U studies.
• Increasingly sensitive VL assays now detect levels below 20 copies/mL, causing definitional confusion.

Purpose of the Study:

• To address confusion surrounding the definition of "undetectable" viral load (VL) in HIV.
• To evaluate the clinical significance of VLs between the lower limit of detection (LLD) and 200 copies/mL.
• To propose improvements in VL reporting and patient counseling regarding HIV transmission.

Main Methods:

• Review of existing studies on U = U and viral load assays.
• Analysis of the implications of highly sensitive VL testing on HIV management.
• Discussion of clinical benefits and potential harms of reporting very low VLs.

Main Results:

• VLs between the LLD (e.g., 20 copies/mL) and 200 copies/mL are associated with future virologic failure.
• No demonstrated clinical benefit exists for intervening in patients with VLs in this range.
• Current reporting practices for low VLs may be harmful due to lack of clear benefit.

Conclusions:

• Overly sensitive VL testing can create confusion and potential harm in the context of U = U.
• Recommendations are made for adjusting VL reporting thresholds and enhancing provider counseling.
• Further research is needed to mitigate harms associated with highly sensitive VL testing and clarify U = U definitions.