HIV viral load

MHurt1 mhurt1 at aol.com
Thu Mar 21 16:25:20 EST 1996


In response to the post:  

HIV-1 plasma viral load assays by PCR are increasingly being used as a
surrogate marker to determine individual response to antiviral
medication, and in treatment decisions on altering such therapy.

Information/discussion is requested on the ability of viral load, as
currently measured in HIV-1 infection, to acurately reflect the
changes in viral population which may be expected under the influence
of RT inhibitors, protease inhibitors, NNRTI's and combinations of
these drugs.

If these agents alter viral production so that defective or
non-functional virions are produced, how would the current assays for
viral load reflect that?

If these agents alter viral production so that non-intact viral
particulate matter is produced instead of intact virions, how would
the current assays for viral load reflect this?

Insight into these questions is crucial to ensure correct management
of therapeutic decisions based on the viral load measure. Obviously,
this measure is redundant if it cannot differentiate between
functional and non-functional virions, or intact virions and particles
of viral components. 

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Yes this does seem to present a problem, possibly a limitation, in using a
PCR assay in a semi-quantitative way to measure "viral load" as a marker
for treatment efficacy.  

Question:  What is the lifespan of a defective virion in circulation?  Do
they persist or are they cleared?

Perhaps a method can be devised by constructing a multiplex system of PCR
assays for various gene products which could be used to find a "common
denominator" of full length transcripts as opposed to those contributed by
defective viral particles.  However, my experience with this technology
tells me that this will be a exceedingly difficult and inexact thing to
do.  Perhaps PCR will in the end be found lacking in its applicability to
this problem.

Yes, I said it.   MAYBE PCR IS NOT THE HOLY GRAIL OF MOLECULAR BIOLOGY! 
Just don't tell anyone you heard it from me! 

Mark H. Hurt
MHurt1 at AOL.COM
AIDS Immunobiology Lab
UCSF/SFGH
San Francisco, CA



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