Document 0721
 DOCN  M94A0721
 TI    Antiretroviral therapy of HIV: a virologists perspective.
 DT    9412
 AU    Corey L; University of Washington, Seattle.
 SO    Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:19 (abstract no.
       TPI-4). Unique Identifier : AIDSLINE ASHM5/94348934
 AB    While the availability of nucleoside reverse transcriptase (RT)
       inhibitors have revolutionised care of HIV infected persons, controversy
       exists about the overall utility of these medications. When should
       therapy be initiated? With what agent? When should alternative therapy
       be utilised, what alternative should be given and when should
       antiretrovirals be stopped? Much of this controversy exists (in this
       persons opinion) because the expectations and questions asked in often
       quoted studies have differed. RT inhibitors differ from most other
       antimicrobials in that they inhibit the frequency of newly infected
       cells, and do not inhibit production from persistently infected cells.
       Moreover, they are all prodrugs with the active triphosphate derivative
       requiring intracellular metabolism. For AZT and D4T this is dependent
       upon cell cycle activation. As such, in vivo inhibition of HIV is only
       partial. All clinical trials of RT inhibitors have stratified patients
       by CD4 cell count. However, a variety of virologic assays indicate that
       viral load whether measured in plasma or PBMCs may differ by as much as
       4 logs among persons with similar CD4 cell counts. In addition, RT
       inhibitors alone inhibit replication by about 1/2 log and in combination
       by 1-1.5 log. As such, the varied effects of these compounds in large
       scale trials is not unexpected. It appears that whether one uses
       monotherapy, combination therapy or sequential therapy, the duration of
       effectiveness is greatest the earlier one initiates therapy. In
       addition, adding or switching to alternative therapy after AZT appears
       to be most effective when CD4 counts are > 150 cells/mm3. In AZT treated
       patients, the effectiveness of any of these current nucleosides (ddl or
       ddC) in those with < 100 CD4 cells is unclear. In these patients
       prophylaxis of opportunistic infections should be optimised. The data
       leading to the above observations will be discussed.
 DE    Antiviral Agents/*THERAPEUTIC USE  Drug Therapy, Combination  Human  HIV
       Infections/*DRUG THERAPY  Leukocyte Count/DRUG EFFECTS
       Prodrugs/THERAPEUTIC USE  Reverse Transcriptase/*ANTAGONISTS & INHIB  T4
       Lymphocytes/DRUG EFFECTS  Virus Replication/DRUG EFFECTS
       Zidovudine/THERAPEUTIC USE  MEETING ABSTRACT

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