Document 2882
 DOCN  M94A2882
 TI    Loviride induces a prolonged rise of the CD4 count in asymptomatic
       HIV-1+ subjects.
 DT    9412
 AU    De Brabander M; Staszewski S; De Cree J; Verhaegen H; Stoffels P; Van
       Den Broeck R; Roels V; Janssen PA; CRU St. Bartholomeus, Merksem,
       Belgium.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):203 (abstract no. PB0242). Unique
       Identifier : AIDSLINE ICA10/94369693
 AB    OBJECTIVE: to compare the effect on CD4 count of treatment with placebo
       or with the alpha-APA compounds R18893 and loviride (R89439) a new
       derivative with improved activity and selectivity and greatly enhanced
       bioavailability (plasma levels > 100x the IC50 for HIV-1) METHODS:
       double blind, double dummy investigation of 24 weeks on 114 evaluable
       participants with baseline CD4 count > 400 or > 20%. Monthly clinical
       and laboratory evaluation. Main parameter CD4 count and percentage
       determined on 3 separate samples to improve accuracy. RESULTS: with
       placebo or R18893 treatment the mean CD4 number fluctuated around
       baseline and the mean CD4% decreased progressively to +/- 95% of
       baseline. Loviride induced a significant increase of the CD4% to +/-
       105% of baseline (p = .035 versus placebo, general linear model with
       mixed effects) The number of CD4 lymphocytes fluctuated between 110-120%
       of baseline up to the end of the study (24 weeks; p = 0.005 versus
       placebo). In the placebo group the number of patients with increased or
       stable CD4 counts fluctuated around 50% while this was 60-70% in the
       loviride group. Both loviride and R18893 were very well tolerated
       (Staszewski et al. this meeting). Sofar, the resistance conferring
       mutations Y-181 or Y106 did not appear in plasma samples (last analysis
       = 3 months, further data available at meeting by Staszewski et al.)
       DISCUSSION AND CONCLUSIONS: loviride treatment produced a long lasting
       rise in the CD4 count in asymptomatic patients in the absence of any
       side effects and without inducing the early appearance of resistant
       virus strains. It appears to be the alpha-APA compound of choice for
       further investigations in mono- and in combination-therapy.
 DE    Acetamides/*PHARMACOLOGY  Acetophenones/*PHARMACOLOGY  Antiviral
       Agents/*PHARMACOLOGY  Comparative Study  Double-Blind Method  Human  HIV
       Infections/BLOOD/*DRUG THERAPY  Leukocyte Count/*DRUG EFFECTS  Reverse
       Transcriptase/*ANTAGONISTS & INHIB  Treatment Outcome  *T4 Lymphocytes
       CLINICAL TRIAL  MEETING ABSTRACT  RANDOMIZED CONTROLLED TRIAL

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