Warning: Viral Replication Is Hazardous to Your Health

September 24, 2011

Paul E. Sax, M.D.

Paul E. Sax, M.D., is director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital in Boston.

When studies evaluate the prognostic importance of measuring HIV viral load, they generally do so by assessing a single measurement rather than values obtained longitudinally. One obvious limitation of this approach is that baseline VL poorly predicts outcome after ART initiation -- a finding in stark contrast to the original description of VL from the MACS cohort prior to effective HIV therapy.

Now, a collaborative group of researchers report the effect of something they call "viremia copy-years," a marker of cumulative exposure to viral replication. This "area under the viral load" curve was calculated in 2027 patients starting ART at eight US sites from 2000-2008. Total number of VL measurements was a whopping 21,665.

The results are striking: viremia copy-years strongly predicted all-cause mortality -- and did so more powerfully than either cross-sectional VL measurements or CD4-cell count. Each 1-unit increase in log10 copy years/mL was independently associated with a 44% increase in mortality risk.

The take-home message from this skillfully done study is that viral replication is bad for your health -- even if your CD4-cell count is OK. And why might this be the case? The authors write:

We speculate the number of viremia copy-years, as a measure of cumulative plasma HIV burden, serves as a surrogate for and perhaps is the underlying driver of cumulative inflammation and immune system activation that approximates such long-term inflammatory biomarker effects.

A few other thoughts:

  • Is high viremia copy-years a lab proxy for poor medication adherence? Probably -- but this doesn't invalidate the results.
  • Of course in clinical practice, few of us have the calculus skills (remember integrals?) actually to calculate something like an area under the viral load curve. OK, I don't have the math skills.
  • A study evaluating whether pre-ART viremia copy-years influences prognosis would be particularly fascinating -- and highly relevant for the when-to-start question.
  • The results reinforce the findings from this interesting study linking time of uncontrolled viral replication to an increased risk of lymphoma -- paper summarized in Journal Watch AIDS Clinical Care.

So even though we are unlikely to start using this viremia copy-years value in clinical practice, these data certainly make intuitive sense -- and reinforce the notion that getting this lethal virus under control is the logical way to improve outcomes.

Paul Sax is Clinical Director of Infectious Diseases at Brigham and Women's Hospital. His blog HIV and ID Observations is part of Journal Watch, where he is Editor-in-Chief of Journal Watch AIDS Clinical Care.

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This article was provided by NEJM Journal Watch. NEJM Journal Watch is a publication of the Massachusetts Medical Society.

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