Experts say a mildly detectable viral load can’t transmit HIV and may be fine treatment-wise

Undetectable equals untransmittable! U=U! It’s a major message among HIV advocates that we’ve been hearing the past decade-plus. And, let’s be clear, the science has long been in: If your HIV virus is sufficiently suppressed on antiretroviral therapy (ART) so that it’s undetectable on a viral-load test―usually meaning these days that it’s below 20 copies per milliliter of blood plasma―then you cannot transmit HIV sexually to others, even if you have condomless sex and your partner is not on the HIV-prevention regimen pre-exposure prophylaxis (PrEP).

But lesser known is research shared by the World Health Organization last summer, that found there is zero possibility of passing on HIV through sex if a person living with HIV has “a viral load less than 200 copies per mL.” Unfortunately, many medical professionals are still unaware of this latest update. As a result, some providers wrongly tell their patients with HIV that they can transmit to sexual partners—just because their viral load is above 20 copies/mL.

That’s why, last October, a group of University of Miami doctors wrote a paper―published in the journal Open Forum Infectious Diseases―saying tests that can detect to as low as 20 have led “to confusion about the definition of ‘undetectable’ and when someone is truly considered untransmittable.” The authors wrote that it is “harmful” for providers to tell patients with viral load between 20 and 200 that they can transmit HIV sexually.

“We suggest recommendations for adjusting viral load reporting and improving provider counseling,” they wrote, “and call for research designs to mitigate the harms of overly sensitive viral load testing.”

In an email to TheBody, David Serota, M.D., M.Sc., one of the paper’s authors, explained further: “We have seen confusion among providers and patients when trying to interpret the meaning of viral loads below 200 copies. The science behind U=U was done more than a decade ago using tests that detected down to 200. The advent of newer and more sensitive tests have created a new goal post for undetectable that in turn has created unnecessary worry. The main point for people living with HIV to know is that based on the best available evidence, as long as their viral load is below 200 copies, there is no risk of sexual transmission of HIV. The verdict is still out on why some people may show these tiny viral load values and whether it could have other effects on the body. Regardless of what impact low viral load levels might have on the body, the recommendation is always going to be to try and optimize adherence to antivirals.”

Don’t Worry About a Low Viral Load If You Are Adhering to Your Medications and Labs Show No Resistance

Meanwhile, a new study in Nature Medicine has some equally soothing news about people with virus detectable up to about 1,000 copies/mL. Detectable virus is usually caused by someone not adhering to their medication properly or by resistance to certain drugs, which can be determined by a so-called genotype test and can be addressed by a medication change or augmentation.

But, in the absence of those factors, what causes low-level detectability?

In this study, the authors determined that such patients had unusually “large and hyperactive reservoirs of HIV [in their bodies] churning out virus,” as one of the authors, Jonathan Li, M.D., M.M.Sc., put it to TheBody on a Jan. 5 call. Li is the director of the Harvard/Brigham Virology Specialty Laboratory and the Harvard University Center for AIDS Research Clinical Core.

He added that we don’t quite know yet why folks with HIV on ART still have active reservoirs—but if we could find out, that might lead to therapies that could stop HIV activity completely. That might reduce or stop the chronic inflammation believed to be caused by HIV, which in turn is believed to be a cause of premature aging in some people with HIV.

But, to the most pressing question—Does this kind of low-level detectability signal treatment failure?—Li gives a firm no. If such patients “are taking their medications every day and there’s no evidence of resistance, then their medications are working exactly as intended.” In other words, there’s no reason to switch or add medications to one’s regimen to try to get to the most current test’s version of undetectable—as there would be if the person actually had drug-resistant virus.

Li’s assessment is echoed by a longtime researcher at University of California, San Francisco, Steven Deeks, M.D., who is also an author on the study. “It’s easy for doctors to say we need to get patients to below 20, but if persisted low-level viremia is occurring [when someone is adherent to their ART, and in the absence of resistance], then piling on more drugs won’t work,” Deeks told TheBody. “You don’t want to add drugs that do nothing but increase expense and toxicity just to get to a level that’s not needed, or that won’t be possible.”

To that point, said Li, “we saw in the study that patients’ low-level viremia eventually went away and got to undetectable.” So maybe, eventually, it is possible.

In fact, Li said, he and colleagues believe that all folks with HIV on ART have some active virus beneath the current 20-copies/mL detectability cut-off—because when they tested folks’ virus on hypersensitive tests that detect below 20, that’s just what they found.

So, what are the takeaways here? One is that providers should not tell patients with detectable virus up to 200 copies/mL that they can transmit HIV sexually, because it’s already been established that they cannot.

The other is important to keep in mind should you (or anyone you know) have detectable HIV as high as about 1,000 copies/mL despite being adherent to your ART and showing no mutations on resistance tests: Relax! Your medications are working.

By Tim Murphy