       Document 0627
 DOCN  M9640627
 TI    Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of
       progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS.
 DT    9604
 AU    O'Brien WA; Hartigan PM; Martin D; Esinhart J; Hill A; Benoit S; Rubin
       M; Simberkoff MS; Hamilton JD; Department of Medicine, West Los Angeles
       Veterans Affairs Medical; Center, CA 90073, USA.
 SO    N Engl J Med. 1996 Feb 15;334(7):426-31. Unique Identifier : AIDSLINE
       MED/96150231
 AB    BACKGROUND. Clinical trials of antiretroviral drugs can take years to
       complete because the outcomes measured are progression to the acquired
       immunodeficiency syndrome (AIDS) or death. Trials could be accelerated
       by the use of end points such as changes in CD4+ lymphocyte counts and
       plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and
       beta 2-microglobulin, but there is uncertainty about whether these
       surrogate measures are valid predictors of disease progression. METHODS.
       We analyzed data from the Veterans Affairs Cooperative Study on AIDS,
       which compared immediate with deferred zidovudine therapy. Patients'
       plasma levels of HIV-1 RNA and beta 2-microglobulin were measured in
       stored plasma. RESULTS. Among the 129 patients in the
       immediate-treatment group, 34 had disease that progressed to AIDS, as
       compared with 57 of the 141 patients in the deferred-treatment group (P
       = 0.03). Progression to AIDS correlated strongly with base-line CD4+
       lymphocyte counts (P = 0.001) and plasma levels of HIV-1 RNA (P <
       0.001), but not with base-line levels of beta 2-microglobulin (P =
       0.14). A decrease of at least 75 percent in the plasma level of HIV-1
       RNA over the first six months of zidovudine therapy accounted for 59
       percent of the benefit of treatment, defined as the absence of
       progression to AIDS (95 percent confidence interval, 13 to 112 percent).
       Plasma beta 2-microglobulin levels and CD4+ lymphocyte counts explained
       less of the effect of treatment. A 75 percent decrease in the plasma
       HIV-1 RNA level plus a 10 percent increase in the CD4+ lymphocyte count
       could explain 79 percent of the treatment effect (95 percent confidence
       interval, 27 to 145 percent). CONCLUSIONS. Treatment-induced changes in
       the plasma HIV-1 RNA level and the CD4+ lymphocyte count, taken
       together, are valid predictors of the clinical progression of
       HIV-related disease and can be used to assess the efficacy of zidovudine
       and possibly other antiretroviral drugs as well.
 DE    beta 2-Microglobulin/ANALYSIS  Acquired Immunodeficiency
       Syndrome/IMMUNOLOGY/*PHYSIOPATHOLOGY/  VIROLOGY  Antiviral
       Agents/*THERAPEUTIC USE  Biological Markers/BLOOD  *CD4 Lymphocyte
       Count/DRUG EFFECTS  Disease Progression  Human  HIV Infections/*DRUG
       THERAPY/IMMUNOLOGY/PHYSIOPATHOLOGY/VIROLOGY  HIV-1/GENETICS/*ISOLATION &
       PURIF  Life Tables  *Outcome Assessment (Health Care)  Regression
       Analysis  Retrospective Studies  Risk  RNA, Viral/*BLOOD  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, Non-P.H.S.  Zidovudine/*THERAPEUTIC
       USE  JOURNAL ARTICLE

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

