Document 1122
 DOCN  M94A1122
 TI    Characteristic features of non-nucleoside reverse transcriptase
       inhibitors (NNRTIs) as HIV-1-specific RT inhibitors.
 DT    9412
 AU    De Clercq E; Rega Institute for Medical Research, Katholieke
       Universiteit; Leuven, Belgium.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):204 (abstract no. PB0830). Unique
       Identifier : AIDSLINE ICA10/94371453
 AB    Various classes of compounds [i.e. TIBO, HEPT, TSAO, alpha-APA; globally
       referred to as non-nucleoside reverse transcriptase (RT) inhibitors
       (NNRTIs)] have been described as potent and selective inhibitors of
       HIV-1 replication. NNRTIs differ in several aspects from the
       dideoxynucleoside (ddN) type of RT inhibitors: they do not require
       intracellular metabolism, interact non-competitively [with regard to the
       natural substrate (dNTP)] with an allosteric, non-substrate binding
       site, exhibit a remarkably high specificity for the HIV-1 RT, and
       rapidly lead to the emergence of virus-drug resistance, due to specific
       mutations in their RT binding site. However, NNRTIs not necessarily lead
       to cross-resistance to one another, which means that if resistance
       develops to one of the NNRTIs, treatment could be switched to another
       NNRTI to which the virus has remained sensitive. Also, the mutations
       underlying resistance to different RT inhibitors may antagonize each
       other, which then would provide a rational basis for selecting the
       appropriate drug combinations. Whether used as such or in combination,
       NNRTIs could, if given from the start at a sufficiently high
       concentration, completely suppress (knock-out) virus replication and
       thus prevent breakthrough of any virus whether drug-resistant or not.
 DE    Drug Resistance  HIV-1/*DRUG EFFECTS/GROWTH & DEVELOPMENT  Reverse
       Transcriptase/*ANTAGONISTS & INHIB  MEETING ABSTRACT

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