Document 0285
 DOCN  M9590285
 TI    Recent advances in nucleoside therapy.
 DT    9509
 AU    Pinching AJ; Department of Immunology, Medical College of Saint
       Bartholomew's; Hospital, West Smithfield, London, UK.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:228 (unnumbered
       abstract). Unique Identifier : AIDSLINE ASHM6/95291814
 AB    This talk will focus primarily on the three best studied nucleoside
       analogues-zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC)-in
       symptomatic HIV disease and on AZT in asymptomatic HIV infection. AZT
       has well established efficacy in symptomatic disease, achieving a
       slowing of disease progression, with fewer opportunist infections in the
       first year or so and improved survival. While this benefit is modest and
       probably limited in duration, it is not possible to define a duration of
       efficacy for the individual. In addition, AZT can partially reverse the
       signs of HIV encephalopathy, being the only treatment for this aspect of
       the disease; it has a substantial effect in reducing the incidence of
       encephalopathy if used before its onset. AZT is also of value in HIV
       associated thrombocytopenia. While ddI and ddC are probable comparably
       effective to AZT as monotherapy, the latter is the drug of first choice.
       Some studies suggest that switching from AZT to ddI may confer benefit
       over continuing AZT, and it is possible that ddC has a similar effect.
       However, this effect does not appear to be due to the emergence of
       resistance to AZT, as the correlation between resistance and clinical
       outcome is irrespective of continuing AZT or switching to ddI. The
       formulation of ddC is generally preferred to ddI by most patients,
       though data on ddI efficacy are more substantial. Didanosine and
       probably zalcitabine have minimal effect on HIV encephalopathy.
       Combination therapy with two nucleosides is of considerable interest as
       a means of achieving greater efficacy and large studies are currently
       pending. Early hopes that zidovudine would be of value in slowing
       progression to symptomatic disease when given to asymptomatic HIV
       infected subjects have been undermined by the Concorde trial. While the
       concept of early intervention remains valid and while AZT may indeed be
       of benefit to a yet to be defined subpopulation, there appears to be no
       clinically relevant benefit to the generality of asymptomatic
       individuals. Two recent studies have shown that HIV suppression by
       zidovudine can also affect transmission; if given from the second
       trimester through to early neonatal life, it appears to reduce the risk
       of vertical transmission; in an observational study, some evidence has
       been adduced to indicate reduced transmission to regular sexual
       partners. Nucleoside monotherapy remains the mainstay of current
       antiviral approaches to HIV disease, despite its evident limitations.
       Whether combinations of nucleosides, or combinations of nucleosides with
       other agents will fulfil the promise that is currently being invested in
       them remains to be established in trials with clinical end-points.
 DE    Antiviral Agents/*THERAPEUTIC USE  Comparative Study
       Didanosine/THERAPEUTIC USE  Drug Therapy, Combination  Human  HIV
       Infections/*DRUG THERAPY  Nucleosides/*THERAPEUTIC USE  Treatment
       Outcome  Zalcitabine/THERAPEUTIC USE  Zidovudine/THERAPEUTIC USE
       MEETING ABSTRACT

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