As HIV RNA tests become ever more capable of detecting minute quantities of the virus, health care providers and laboratories should be more mindful of how viral load results can be misinterpreted in the era of ‘Undetectable equals Untransmittable’ (U=U). Although HIV is not passed on through sex with a viral load below 200 copies/ml, people living with HIV may receive lab reports showing that their result as, for example, “HIV-1 RNA detected, 35 copies/ml” and be confused about whether U=U applies to them, argue Maria Rodriguez and colleagues at the University of Miami in the journal Open Forum Infectious Diseases.
The key studies showing the link between viral load and sexual transmission of HIV all used a threshold of 200 copies/ml, and found that no study participants with a viral load below this level passed on HIV. And while the messaging used to communicate this has focused on the word ‘undetectable’, modern lab tests are in fact capable of detecting smaller quantities of virus.
For example, Abbott’s RealTime viral load assay has a “lower limit of detection” of 40 copies/ml. Using this test, a patient might have their viral load reported as “not detected”, which indicates that the assay was unable to detect any virus in the blood sample tested. Alternatively, their result might be reported as “<40 copies/ml”, which indicates that the test picked up a tiny trace of HIV, which was too small for the test to give an accurate estimate of the number of copies. Other people’s results might give a specific figure, indicating how many copies of the virus were in the blood sample, for example 50 copies/ml or 100 copies/ml.
Other commonly used tests have lower limits of detection of 10, 20, 30, 40 or 50 copies/ml. Test results may be reported in similar ways, often with the phrase “HIV-1 RNA detected” if a specific value is given. However, as long as the number of copies is 200 or less, a person’s viral load is low enough to be considered ‘undetectable’ and there is zero risk of HIV transmission during sex.
The authors say this can be confusing for people living with HIV. They give the example of a young woman who had recently been diagnosed with HIV and started HIV treatment. She had been told that with time and good adherence, she would achieve an “undetectable” viral load and be non-infectious to sexual partners. For two years, her test results were consistently above the 20 copies/ml lower limit of detection of the assay used, but remained below 200 copies/ml. Although her doctor explained that a sustained viral load below 200 copies/ml meant that the virus was untransmittable, she became increasingly frustrated about being unable to achieve an “undetectable status” based on her lab results.
“She was skeptical about her lack of infectiousness, was dissatisfied with her ART, and was reticent to engage in sexual relationships, which she had avoided since her diagnosis,” the authors write. “For patients, seeing a detectable viral load reported but being told they are untransmittable sows confusion and may challenge beliefs in the otherwise clear U = U message, as it did in this patient case.”
Viral load results are also important for other aspects of patient care, but there are no clear data showing the clinical relevance of results below 200 copies/ml. One exception is that a viral load between 20 and 200 copies/ml on two or more consecutive tests is associated with future virological failure, but the authors argue that it is not clear that identifying this low-level viraemia leads to actions which are effective in preventing virological failure.
“Because viral loads deemed detectable but <200 copies/mL have not demonstrated meaningful clinical implications, and have the potential to cause confusion and mistrust among patients and providers alike, we consider reporting these values to be a harmful medical practice with a negative public health message,” they say.
They recommend exploring new ways to report and discuss viral load results with patients. One option would be for the laboratory report to include the words “no risk of sexual transmission” when viral load is below 200 copies/ml. Alternatively, all viral loads below this level could be automatically reported as “undetectable”, with the precise value hidden but available to clinicians to disclose with further explanation if needed.
Healthcare providers should spend more time ensuring that the term “undetectable” is equated specifically with a viral load below 200 copies/mL rather than leaving people to look for the words “not detected” in laboratory results. People with HIV could be encouraged to focus on the number 200, with it being explained that the goal for HIV treatment is a viral load of less than 200 and a CD4 count above 200.
Rodriguez MG et al. The Perils of Overly Sensitive Viral Load Testing for Persons With Human Immunodeficiency Virus, Open Forum Infectious Diseases 10: ofad494, 2023 (open access).