home
***
CD-ROM
|
disk
|
FTP
|
other
***
search
/
Shareware Overload Trio 2
/
Shareware Overload Trio Volume 2 (Chestnut CD-ROM).ISO
/
dir26
/
med9410o.zip
/
M94A2884.TXT
< prev
next >
Wrap
Text File
|
1994-10-25
|
3KB
|
48 lines
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).