       Document 0463
 DOCN  M9550463
 TI    HIV therapy advances. Update on a proteinase inhibitor.
 DT    9505
 AU    Vella S; Laboratory of Virology, Istituto Superiore di Sanita, Rome,;
       Italy.
 SO    AIDS. 1994 Sep;8 Suppl 3:S25-9. Unique Identifier : AIDSLINE
       MED/95142950
 AB    HIV PROTEINASE INHIBITORS: The HIV proteinase enzyme has been identified
       as a potential target for antiretroviral therapy, as inhibition of this
       enzyme leads to the generation of immature, non-infectious virions.
       There are several proteinase inhibitors in development; the first to
       enter clinical trials was saquinavir. DEVELOPMENT OF SAQUINAVIR:
       Saquinavir, a transition-stage analogue of an HIV proteinase cleavage
       site, was developed using computer-led rational design techniques. It is
       a highly specific inhibitor of HIV-1 and -2 proteinases, with antiviral
       activity at concentrations 1000-fold less than those causing
       cytotoxicity. EUROPEAN CLINICAL EXPERIENCE WITH SAQUINAVIR: Three
       European clinical studies involving 202 patients have been conducted
       with saquinavir at doses of 25, 75, 200 and 600 mg three times a day.
       Two studies were dose-ranging monotherapy trials, one in asymptomatic or
       mildly symptomatic patients not previously treated with zidovudine, the
       other in patients with advanced HIV infection who had been treated with
       zidovudine. The third study was a combination therapy trial with
       zidovudine in previously untreated patients with advanced infection.
       Saquinavir was well tolerated either alone or in combination with
       zidovudine. In the monotherapy studies, CD4 cell counts and estimates of
       viral load showed the best results with the 600-mg dose. The combination
       of saquinavir and zidovudine resulted in higher and more sustained
       increases in CD4 cell counts than with either drug alone. The CD4 cell
       counts favoured saquinavir at 200 and 600 mg in combination with
       zidovudine, although plasma viraemia and the RNA polymerase chain
       reaction indicated that the 600-mg dose (in combination) produced better
       responses.
 DE    Aspartic Proteinases/METABOLISM  Cell Line  Clinical Trials  Female
       Human  HIV/*DRUG EFFECTS/ENZYMOLOGY/ULTRASTRUCTURE  HIV Infections/*DRUG
       THERAPY  HIV Protease/METABOLISM  HIV Protease
       Inhibitors/CHEMISTRY/*THERAPEUTIC USE
       Isoquinolines/CHEMISTRY/*THERAPEUTIC USE  Male
       Quinolines/CHEMISTRY/*THERAPEUTIC USE  Randomized Controlled Trials
       JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

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

