COMMENTARY

Low-Level Viremia in HIV: When Should We Worry?

Paul E. Sax, MD

Disclosures

March 11, 2020

This transcript has been edited for clarity.

Hello. This is Dr Paul Sax from Brigham and Women's Hospital and Harvard Medical School. Today I'd like to discuss a paper published in Clinical Infectious Diseases that covers one of the more vexing topics in outpatient HIV care: low-level viremia.

Some studies have suggested that this low-level viremia, often defined as viral load between 50 and 200 copies/mL, is benign and not associated with subsequent virologic failure. Other studies have reported just the opposite, and, of course, there is a wide range of definitions used, how many results are in this category, etc.

To look at this further, a group from the US Military HIV Natural History Study decided to evaluate their patients who had started antiretroviral therapy since 1996 and had sufficient viral loads measured afterwards.

They found 2006 patients in their cohort and assigned them to one of four categories: (1) continuous virologic suppression, which included about half the cohort; (2) intermittent low-level viremia, defined as having < 25% of assays in the range of 50-199 copies/mL, which was about 370 patients; (3) continuous low-level viremia, with more than 25% of assays between 50 and 199 copies/mL; and (4) at least one viral load > 200 copies/mL, which included about 390 patients.

The outcome of interest was confirmed virologic failure, which meant that there was more than one viral load assay > 200 copies/mL. They found that, indeed, continuous low-level viremia was a risk factor for confirmed virologic failure, with an odds ratio of 3.46, which was highly statistically significant. This was not observed in the patients who had intermittent low-level viremia; most of them experienced blips.

The authors concluded that this is a biologically important finding, and they also postulated about the possible causes. Of course, medication adherence could be one of them, or other factors that lead to low drug exposures, meaning if there was a pharmacokinetic interaction or some pharmacy error.

I think we all have patients in whom adherence is 100% perfect, and yet they continue to have a low-level result that we somehow can't get rid of. This raises the question of whether all patients with low-level viremia are the same or if there is a subset of two different groups—one group that may have struggled with adherence at times and another group that may have a very high reservoir and release virions periodically that are not replicating in the presence of subtherapeutic concentrations of the drug.

I think that's probably the case. Cohort studies like this really can't answer the question about how best to manage them, aside from the fact that you want to reinforce good medication adherence. Of course, these days you should have the patient on a regimen with a high resistance barrier.

We can add this latest paper to the long list of other papers that describe this phenomenon of persistent low-level viremia. Maybe we'll eventually have some clear guidance on how to manage these patients. Thanks very much for listening.

Paul E. Sax, MD, is a professor of medicine at Harvard Medical School and clinical director of the Division of Infectious Diseases at Brigham and Women's Hospital. His research interests include antiretroviral therapies, the cost-effectiveness of HIV management strategies, and complications of antiretroviral treatment. He blogs at HIV and ID Observations and has been a Medscape contributor since 2008.

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