       Document 0590
 DOCN  M9610590
 TI    Viral load in peripheral blood mononuclear cells as surrogate for
       clinical progression.
 DT    9601
 AU    Ferre F; Moss RB; Daigle A; Richieri SP; Jensen F; Carlo DJ; Immune
       Response Corporation, Carlsbad, CA 92008, USA.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10 Suppl 2:S51-6.
       Unique Identifier : AIDSLINE MED/96033812
 AB    During the symposium on surrogate markers of HIV, the Scientific
       Advisory Committee posed the following question: Which surrogate markers
       currently deserve the greatest commitment of investigative resources to
       validate them in a clinical setting? The Committee concluded that for
       antiretroviral drugs measurements of HIV RNA in plasma deserve the
       greatest priority, and for immune-based therapies assessing viral load
       still had the highest priority. But it was recognized that assessing
       viral load should not be restricted to plasma RNA because the primary
       mechanisms of action are different from antiretroviral drugs. Thus, the
       Committee voted that based on current knowledge, investigating the
       clinical relevance of changes in HIV-1 DNA and RNA copy number in
       peripheral blood mononuclear cells (PBMCs) with validated assays should
       be given equal focus for immune-based therapies. This article reviews
       the rationale for using HIV-1 DNA and RNA load in PBMCs for the
       monitoring of clinical trials and presents recent data that indicate
       that the postseroconversion level and the dissemination of proviral DNA
       in the blood cells have prognostic value, i.e., high levels correlate
       with disease progression. In addition, longitudinal studies show that an
       increase in proviral DNA and/or HIV mRNA load correlates with disease
       progression. We present evidence that these markers are relevant
       activity markers for anti-HIV therapies. Changes in both DNA and RNA
       load can be achieved using either antiretroviral drugs or immune-based
       therapies. These results suggest that these markers should be evaluated
       in clinical studies to firmly establish their value as surrogates of
       clinical progression.
 DE    Biological Markers  Disease Progression  DNA, Viral/BLOOD  Human  HIV
       Infections/BLOOD/THERAPY/*VIROLOGY  HIV-1/*GENETICS/ISOLATION & PURIF
       Leukocytes, Mononuclear/*VIROLOGY  Proviruses/*GENETICS/ISOLATION &
       PURIF  RNA, Viral/BLOOD  JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

