       Document 0742
 DOCN  M9630742
 TI    HIV viral load quantification, HIV resistance, and antiretroviral
       therapy.
 DT    9603
 AU    Katzenstein DA; Holodniy M; Stanford University School of Medicine,
       California, USA.
 SO    AIDS Clin Rev. 1995-96;:277-303. Unique Identifier : AIDSLINE
       MED/96089203
 AB    We are moving rapidly beyond a black box understanding of the
       pathogenesis of HIV. The sites of virus replication, the molecular
       regulation of virus production in the host, and the dynamics between
       productive virus infection and immunological and clinical events are
       areas of intense study using powerful new tools. The quantitation of
       virus load and genetic characterization of replicating virus has
       important implications for the development and evaluation of drugs and
       treatment strategies for HIV. As new compounds are introduced, their
       ability to reduce virus load in vivo has become a primary consideration
       in the decision to initiate large efficacy trials and may soon be used,
       in combination with other markers, in the licensing of new agents. In
       parallel, rapid molecular evaluation of virus from patients, targeting
       those who break through drug-induced suppression, provides an
       explanation for the failure of drugs to sustain an effect on virus load.
       This approach has compressed the process of drug evaluation and set the
       stage for the evaluation of complex combinations and sequences of drugs
       to maintain suppression of virus and prevent the development of drug
       resistance. The most controversial question for the next few years is
       whether the measurement of virus load or detection of drug resistance
       can be incorporated into the practice of medicine and the management of
       individual patients. There is evidence that changes in virus load are
       the most proximate markers of drug response and that detection of
       resistance mutations can predict clinical and immunological decline.
       However, the window of time between a change in load or the development
       of drug resistance and a decline in CD4 cells is relatively short. With
       dideoxynucleoside therapies, a CD4 cell decline follows a rise in virus
       load or development of resistance within 3-6 months. In early studies
       with protease inhibitors and nonnucleoside reverse transcriptase
       inhibitors, the development of resistance and a return to baseline of
       virus load may occur within 2-3 months, mirrored by a fall in CD4 cells.
       The challenge to investigators is how to best use these new tools to
       determine whether changes or additions in therapy, initiated on the
       basis of virological measurements, result in more effective management
       of disease.
 DE    Antiviral Agents/*THERAPEUTIC USE  Drug Resistance, Microbial  DNA,
       Viral/ANALYSIS  Human  HIV/DRUG EFFECTS/*ISOLATION & PURIF  HIV Core
       Protein p24/ANALYSIS  HIV Infections/DRUG THERAPY/*VIROLOGY  Lymph
       Nodes/VIROLOGY  RNA, Viral/ANALYSIS  JOURNAL ARTICLE  REVIEW  REVIEW,
       ACADEMIC

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

