Document 2884
 DOCN  M94A2884
 TI    Panavir: a novel therapy for HIV infection.
 DT    9412
 AU    Hendler SS; Sanchez RA; Nagourney RA; Lauermann MW; Sonne M; Strayer G;
       Vyrex Corp., La Jolla, CA 92037.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):202 (abstract no. PB0238). Unique
       Identifier : AIDSLINE ICA10/94369691
 AB    OBJECTIVE: To assess a) the in-vitro activity of Panavir
       (4,4'-isopropylidenedithio-bis-2,6-di-t-butylphenol; a
       specially-formulated lipophilic antioxidant) against HIV replication and
       against activation of latently infected cells, and b) the clinical
       safety, pharmacokinetics, and efficacy in the treatment of HIV disease.
       METHODS: In-vitro activity was measured by syncytia and p24 reduction
       assays in both CEM-ss and Molt 3 cells. The III-B strain of HIV-1 was
       used. Resistance of HIV to Panavir was assayed in CEM-ss cells using
       various HIV strains. The FDA-sanctioned clinical studies were in 25
       adult HIV-positive patients who were not on other antiretroviral
       therapies, and who had CD4 counts ranging from less than 10 to 500. The
       trial began in July of 1992. The safety, PK and dose escalation phase is
       near completion. RESULTS: The ID50 of Panavir in CEM-ss and Molt-3 cells
       was approximately 10 micrograms/ml. Cell toxicity was not seen. Panavir
       inhibits TNF-alpha stimulated production of HIV-1 in OM-10.1 cells. No
       resistance of HIV-1 against Panavir is observed to date (> 6 months).
       Clinically, all patients tolerated the drug well without significant
       side effects. All asymptomatic patients remained asymptomatic with
       stable CD4 counts. One patient with a CD4 count of less than 10 when he
       started the study in July 1992 remains clinically stable. DISCUSSION AND
       CONCLUSIONS: Panavir is a novel anti-HIV drug with demonstrated in-vitro
       activity against actively replicating HIV and against activation of
       latently activated cells. Oxidative stress is a known activator of HIV
       replication in latently infected cells and appears to be involved in
       apoptotic events leading to the death of CD4+ cells. Thus, Panavir may
       have multiple effects as an anti-HIV agent, an antioxidant, and an
       antiapoptotic. Clinical studies show Panavir to be safe. Preliminary
       findings suggest that it slows down the progression of HIV disease.
 DE    Antioxidants/PHARMACOLOGY/THERAPEUTIC USE  Antiviral
       Agents/PHARMACOLOGY/*THERAPEUTIC USE  Apoptosis/DRUG EFFECTS  Cells,
       Cultured  Cytopathogenic Effect, Viral/DRUG EFFECTS  Drug Resistance,
       Microbial  Human  HIV Core Protein p24/ANALYSIS  HIV Infections/*DRUG
       THERAPY  HIV-1/*DRUG EFFECTS/IMMUNOLOGY/PHYSIOLOGY
       Probucol/PHARMACOLOGY/*THERAPEUTIC USE  Treatment Outcome  Virus
       Replication/DRUG EFFECTS  CLINICAL TRIAL  MEETING ABSTRACT

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