Document 0262
 DOCN  M95A0262
 TI    Comparative anti-HIV evaluation of diverse HIV-1-specific reverse
       transcriptase inhibitor-resistant virus isolates demonstrates the
       existence of distinct phenotypic subgroups.
 DT    9510
 AU    Buckheit RW Jr; Fliakas-Boltz V; Decker WD; Roberson JL; Stup TL; Pyle
       CA; White EL; McMahon JB; Currens MJ; Boyd MR; et al; Virology Research
       Group, Southern Research Institute-Frederick; Research Center, MD
       21701-4766, USA.
 SO    Antiviral Res. 1995 Mar;26(2):117-32. Unique Identifier : AIDSLINE
       MED/95328856
 AB    We have biologically and biochemically evaluated a structurally diverse
       group of HIV-1-specific reverse transcriptase (RT) inhibitors and
       determined that the members of this class share many common properties.
       These include reproducible and selective antiviral activity against a
       panel of biologically distinct laboratory and clinical strains of HIV-1,
       activity against HIV-1 in a wide variety of cultured and fresh human
       cells, and potent inhibition of HIV-1 RT when evaluated using a
       heteropolymeric ribosomal RNA template assay. Each of the HIV-1-specific
       compounds was capable of inhibiting HIV replication when challenged at
       high m.o.i., further distinguishing them from the nucleoside analogs
       3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). When
       tested in combination with AZT, each of the HIV-1-specific compounds
       synergistically inhibited the replication of HIV-1. HIV-1 isolates
       resistant to different HIV-1-specific inhibitors exhibited heterogeneous
       patterns of cross-resistance to other members of this pharmacologic
       class. Four distinct phenotypic classes have been defined through the
       use of drug-resistant virus isolates which derive from distinct
       mutations in the RT. These results indicate that the various subgroups
       of HIV-1-specific inhibitors interact differently with HIV-1 RT,
       suggesting important potential implications for drug combination
       therapeutic strategies.
 DE    Antiviral Agents/*PHARMACOLOGY  Cell Line  Comparative Study  Drug
       Evaluation  Drug Interactions  Drug Resistance, Microbial  Human
       HIV-1/*DRUG EFFECTS  Phenotype  Reproducibility of Results  Reverse
       Transcriptase/*ANTAGONISTS & INHIB  Support, U.S. Gov't, P.H.S.
       Zidovudine/PHARMACOLOGY  JOURNAL ARTICLE

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