The HIV Research Takeaway: Does Low-Level Viremia Spell Doom for Your Antiretroviral Regimen?

In The HIV Research Takeaway, we provide plain talk about new data in the world of HIV-related research, and explain in straightforward terms what the results mean for people living with or affected by HIV.

The Issue: "Low-Level HIV Viremia"

David Alain Wohl, M.D.
David Alain Wohl, M.D.

By now, everyone living with HIV knows that the gold medal for virus management goes to those who get their viral loads down to needle-in-a-haystack levels. Such an "undetectable" viral load, or HIV RNA level, means that there is so little virus in the blood that the tests used to count it can't 'see' it. This does not mean there are absolutely no viral particles floating around, just that they are so few and far between that tests are unable to reliably detect them.

Nowadays, HIV viral load tests have gotten so good that they can detect as few as 20 HIV virus copies in the vast sea of a drop of blood. Just a few years ago, the best tests called it quits when a viral load was 400 HIV copies in a drop of blood.

Super-sensitive HIV tests are great, but what does it mean when they find that someone has a really low level of virus, say, 150 copies or 50 copies? Does it mean anything when someone has a transient blip and the virus goes from undetectable up to a low level and then back down again? Does it mean anything that some people seem to keep a simmering low level of virus? Are these worrisome harbingers of imminent loss of control of HIV?

These are some of the questions that a group of researchers in Barcelona tried to answer. They compared rates of virologic failure of therapy among people with low levels (less than 1000 copies) of detected virus and those with persistently undetectable HIV RNA levels and tracked.

These are some of the questions that this paper from a group of researchers in Barcelona tried to answer. They compared the rates of virologic failure of therapy over time among people with low level levels (less than 1,000 copies per mL) of detected virus and those with persistently undetectable HIV RNA levels.

The study was published online on Jan. 12, 2016, in the journal Antiviral Therapy. The lead author is Jordi Navarro. The study title is, "Impact of low-level viraemia on virological failure in HIV-1 infected patients with stable antiretroviral treatment."

The Data

The researchers started by looking at over 1,730 HIV-positive people seen in their clinic between 2011 and 2014 who were on HIV meds and had viral loads below 25 copies per mL of blood (the lower limit of the test they used) for at least six months. Of this group of people -- who by all measures had excellent control of their HIV -- 300 (17%) had some low-level virus detected during the observation period. For most, the virus levels detected were low (between 25 and 50 copies), but one-third or so had viral loads between 50 and 200, and 7% had a worrisome level of between 200 and 1000.

In two-thirds of the participants with low-level virus, the rise in virus level was a one-time deal -- a blip -- and after that their viral load fell back to undetectable. However, in 26% of the participants, two tests in a row showed detectable low-level virus.

Over 7% of those with some form of low-level virus went on to experience virologic failure, defined by the researchers as two tests in a row with a viral load over 200. In contrast, only 1.5% of the 203 participants with persistently controlled virus later had virologic failure.

To determine what predicted virologic failure, the team dumped a bunch of participant characteristics and treatment factors into a computer model. This found that the risk of virological failure was associated with having a viral load between 200 and 1000, or being on HIV treatment with either

  1. a two-drug regimen of a ritonavir-boosted protease inhibitor plus only one other drug (such as a non-nucleoside, an integrase inhibitor or 3TC) or
  2. a ritonavir-boosted protease inhibitor alone.

Blips were not, I repeat, not associated with loss of virologic control. But what about having a persistent low-level virus below 200 copies? That was harder to assess. It looked as if low-level HIV RNA was associated with a heightened risk of failure, but there were few participants (only 27) in this category and it is pretty easy for such people to cross over the 200-copy threshold. Anyway, a good number of these participants regained viral suppression without any change to their HIV medications.

The Takeaway

The good news is that fewer than one out of ten participants with low-level virus went on to experience virologic failure -- even according to the pretty strict definition of failure used by the researchers. The risk of such failure was greatest for those with a viral load between 200 and 1000.

As seen in other studies, the odds of a runaway viral load among those with lower levels of virus were very low -- but higher than for those who had undetectable HIV RNA levels. In some cases, the low levels of HIV that the test detects in the blood are just the virus moving from cells where it had been latent (asleep) and not a sign that HIV medications are not doing their job.

Funky boosted-protease inhibitor minimalistic combinations, more popular in Europe than the U.S., were also a risk for a virologic failure. To be fair, people on such regimens generally had more treatment experience and therefore possibly more problems with drug resistance and adherence. However, there are concerns about such regimens, particularly the use of a boosted-protease inhibitor alone.

In sum, HIV-positive people who have blips and low-level viral loads under 200 copies per mL despite good adherence to their HIV medications should be reassured by these results.

David Alain Wohl, M.D., is an associate professor of medicine in the Division of Infectious Diseases at the University of North Carolina (UNC).