September 24th, 2011

Warning: Viral Replication is Hazardous to Your Health

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.

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HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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