Document 0384
 DOCN  M9590384
 TI    Quantitative virology in assessment of a new anti-retroviral agent.
 DT    9509
 AU    Dwyer DE; Chang J; Dowton DN; Randle C; Armato T; Fordham MS; Cunningham
       AL; Department of Virology, ICPMR, Westmead Hospital.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:104 (unnumbered
       abstract). Unique Identifier : AIDSLINE ASHM6/95291715
 AB    Quantitative HIV isolation from plasma and PBMC, and quantitative RNA
       (plasma) and DNA (PBMC) PCR are the major ways of assessing reduction in
       viral load with new anti-retroviral therapy. Three Australian centres
       have enrolled 15 patients in an international multicentre trial of 100
       patients with a new non-nucleoside reverse transcriptase inhibitor,
       U90152S (a bisheteroarylpiperazine). Patients initially received either
       two dose levels, an escalating dosage regimen or placebo for 12 weeks,
       followed by a further 12 weeks of therapy depending on drug tolerance.
       Enrollment was completed in June 1994, with the last patient due to
       complete the trial by October 1994. Quantitative HIV isolation in PBMC
       and plasma was performed in real time using a standard ACTG approved
       protocol. In 7 patients who have reached week 12 to date, 6 had a
       significant decrease in quantitative PBMC cultures (measured by
       TCID50/10(6) donor cells, using Reed-Meunch calculation) over 12 weeks,
       with 2 then showing increasing quantitative PBMC cultures by 8-12 weeks,
       although not to pre-trial level. Plasma cultures were positive in only 2
       patients. To minimise intra-laboratory variation, quantitative RNA and
       DNA PCR will be performed at the one time on all samples from an
       individual at completion of their trial involvement. Patients PCR
       results are compared to RNA and DNA standard curves generated within the
       laboratory and expressed as HIV copies per ml of plasma (RNA) or per
       400,000 cells (DNA). Preliminary results suggest that U90152S has a
       significant although probably transient effect on viral load, and that
       these techniques are useful in measurement of new anti-retroviral
       efficacy. An expanded international multicentre trial using this agent
       will commence in Australia in mid-1994.
 DE    Antiviral Agents/*THERAPEUTIC USE  Dose-Response Relationship, Drug
       Human  HIV/*DRUG EFFECTS/ISOLATION & PURIF  HIV Infections/*DRUG
       THERAPY/VIROLOGY  Indoles/*ADMINISTRATION & DOSAGE
       Piperazines/*ADMINISTRATION & DOSAGE  Polymerase Chain Reaction/*METHODS
       Virus Replication/DRUG EFFECTS  MEETING ABSTRACT  MULTICENTER STUDY

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