Document 1102
 DOCN  M94A1102
 TI    A pilot phase I study of oral monotherapy with U-87201E (atevirdine,
       ATV) in late stage HIV disease. RV-65 Study Group.
 DT    9412
 AU    Wagner KF; Mayers DL; Cox SR; Batts DH; MMCARR, Rockville, MD.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):209 (abstract no. PB0848). Unique
       Identifier : AIDSLINE ICA10/94371473
 AB    OBJECTIVE: Six patients (pts) with AZT-resistant HIV isolates were given
       ATV, 600 mg tid x 6 as a loading dose, then 400 mg tid to maintain drug
       levels at < or = 30 microM peak and trough levels between 10-20 microM.
       HIV isolates were evaluated to determine the time course of ATV
       resistance. METHODS: Pts were followed daily x 7days, then weekly.
       Pharmacokinetic evaluations were performed at frequent intervals and
       dosage adjusted to maintain target drug levels. HIV-1 drug
       susceptibility testing was performed with the ACTG-DoD protocol.
       Multiple clones of the reverse transcriptase gene (codons 1-250) were
       sequenced for viral isolates with altered drug susceptibility.
       Neuropsychologic evaluations were performed with no significant changes.
       RESULTS: Pts entered study with a mean CD4 count of 56 +/- 26.8/mm3 and
       mean exposure to AZT of 32.4 +/- 3.5 mo. 4/6 pts developed a
       maculopapular skin rash at 11-15 days. Skin bx showed no specific
       features of an acute hypersensitivity reaction or vasculitis. Pts
       entered study with ATV IC50 values that ranged from 0.001 microM to 2.6
       microM. For 3/6 pts, HIV isolates increased ATV IC50 to > 10 microM (2)
       or > 100-fold (1) during the course of therapy. p24 Ag and CD4 levels
       were not significantly altered due to small sample size and brief period
       of trial (33 wk). CONCLUSION: ATV given as high loading dose in pts with
       advanced HIV disease may be associated with an intolerable rate of rash.
       Drug resistance to ATV develops rapidly in this pt population.
 DE    Administration, Oral  Antiviral Agents/*ADMINISTRATION & DOSAGE/ADVERSE
       EFFECTS/  THERAPEUTIC USE  Human  HIV Infections/*DRUG
       THERAPY/MICROBIOLOGY  HIV-1/ISOLATION & PURIF  Pilot Projects
       Piperazines/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/THERAPEUTIC  USE
       CLINICAL TRIAL  CLINICAL TRIAL, PHASE I  MEETING ABSTRACT

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