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M94B0813.TXT
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1994-11-11
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Document 0813
DOCN M94B0813
TI Effects of U-75875, a peptidomimetic inhibitor of retroviral proteases,
on simian immunodeficiency virus infection in rhesus monkeys.
DT 9412
AU Martin LN; Soike KF; Murphey-Corb M; Bohm RP; Roberts ED; Kakuk TJ;
Thaisrivongs S; Vidmar TJ; Ruwart MJ; Davio SR; et al; Tulane Regional
Primate Research Center, Covington, Louisiana; 70433.
SO Antimicrob Agents Chemother. 1994 Jun;38(6):1277-83. Unique Identifier :
AIDSLINE MED/94379779
AB U-75875 inhibits human immunodeficiency virus types 1 and 2 and simian
immunodeficiency virus (SIV) proteases and blocks Gag-Pol protein
processing and viral maturation and replication in vitro. Rhesus monkeys
were treated with vehicle alone or with formulated U-75875 at doses of 7
or 20 mg/kg of body weight per day for 26 days by continuous intravenous
infusion beginning 6 h prior to intravenous inoculation with 10 monkey
50% infectious doses of SIV Delta B670, and the monkeys were monitored
until death. The effects of treatment on the level of SIV p26
antigenemia, the infectious virus titer in serum, and the level of
proviral DNA in blood mononuclear cells evaluated by PCR were assessed.
SIV infection of the controls resulted in an initial viral antigenemia
that began 5 to 10 days postinoculation (p.i.), reached peak values on
days 10 to 14 p.i., and lasted for more than 15 days. Proviral DNA was
detectable in peripheral blood mononuclear cells by 7 to 11 days p.i.,
reached the mean peak level by 11 days p.i., and remained at high levels
through day 24 p.i. Infectious virus was detected in serum from all of
the infected controls by 24 days p.i. Treatment with U-75875 for 26 days
resulted in a dose-related delay in the day of the peak level of
antigenemia (P = 0.034).(ABSTRACT TRUNCATED AT 250 WORDS)
DE Animal Antigens, CD/ANALYSIS Antigens, CD4/ANALYSIS Antiviral
Agents/*THERAPEUTIC USE DNA, Viral/ANALYSIS Female HIV Protease
Inhibitors/*THERAPEUTIC USE Integrins/ANALYSIS Macaca mulatta Male
Oligopeptides/PHARMACOLOGY/*THERAPEUTIC USE Polymerase Chain Reaction
Proviruses/GENETICS Simian Acquired Immunodeficiency Syndrome/*DRUG
THERAPY/ IMMUNOLOGY/PATHOLOGY Support, Non-U.S. Gov't Support, U.S.
Gov't, P.H.S. SIV/DRUG EFFECTS/GROWTH & DEVELOPMENT/ISOLATION & PURIF
T-Lymphocyte Subsets/IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).