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).