       Document 0585
 DOCN  M9610585
 TI    In vitro comparison of selected triple-drug combinations for suppression
       of HIV-1 replication: the Inter-Company Collaboration Protocol.
 DT    9601
 AU    St. Clair MH; Pennington KN; Rooney J; Barry DW; Division of Virology,
       Burroughs Wellcome Co., Research Triangle; Park, NC 27709, USA.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10 Suppl 2:S83-91.
       Unique Identifier : AIDSLINE MED/96033817
 AB    Ten different three-drug combinations have been analyzed for their
       ability to prevent HIV-induced cytopathic effects (CPEs) in a continuous
       human T-lymphoblastoid cell line. Agents acting at the same as well as
       at different sites in the HIV-1 replicative cycle were used. Each
       compound was analyzed at peak and trough plasma levels achieved in
       monotherapy and in the presence of HIV-1 strains 3B and MN at a viral
       inoculum varying from 1 x TCID50 (50% tissue culture inhibitory dose) to
       1,000 x TCID50. Using a viral inoculum of 10 x TCID50 HIV-1 3B, it was
       determined that triple-drug combinations had greater antiviral
       activities than the corresponding double-drug combinations, which had
       greater antiviral activities than zidovudine (AZT) monotherapy. The most
       consistent triple-drug combination, demonstrating superior activity at
       all concentrations of virus, was AZT + dideoxyinosine + lamivudine which
       reduced the AZT IC95 (95% inhibitory concentration) by 208-, 57-, 133-,
       and 25-fold at of 1,000, 100, 10, and 1 x TCID50 HIV-1 3B, respectively,
       as compared with the IC95 for AZT monotherapy. For all antiviral
       regimens tested, higher viral inoculum resulted in less inhibition of
       viral replication and a higher IC95 for AZT. This observation argues for
       therapeutic intervention at an earlier stage in HIV infection, when
       viral burden is lower.
 DE    Antiviral Agents/*PHARMACOLOGY  Cell Line, Transformed  Cytopathogenic
       Effect, Viral/DRUG EFFECTS  Didanosine/PHARMACOLOGY  Drug Synergism
       Human  HIV Protease Inhibitors/*PHARMACOLOGY  HIV-1/*DRUG
       EFFECTS/PHYSIOLOGY  Isoquinolines/PHARMACOLOGY  Pyridines/PHARMACOLOGY
       Quinolines/PHARMACOLOGY  Reverse Transcriptase Inhibitors/*PHARMACOLOGY
       Virus Replication/*DRUG EFFECTS  Zalcitabine/ANALOGS &
       DERIVATIVES/PHARMACOLOGY  Zidovudine/PHARMACOLOGY  JOURNAL ARTICLE

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

