Document 1104
 DOCN  M94A1104
 TI    Dose ranging study of protease inhibitor ABT-987 in HIV-infected
       patients.
 DT    9412
 AU    Gil-Aguado A; Moreno S; Rubio R; Danner S; Alcami J; Garcia de Lomas J;
       Hosp La Paz, Madrid, Spain.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):208 (abstract no. PB0846). Unique
       Identifier : AIDSLINE ICA10/94371471
 AB    ABT-987, a highly selective oral HIV-protease inhibitor, was
       administered to 46 patients divided into four dosage groups for eight
       weeks. The objective of this study was to investigate the tolerability
       and antiviral activity of various dosages of ABT-987. METHODS: An open,
       multicenter study enrolled HIV infected adult patients with CD4 counts
       less than 300 cells/mm3 and p24 antigen > or = 50 pg/mL OR CD4 < or = 50
       cells/mm3 and p24 levels of 20-49 pg/mL. Patients were randomized to one
       of four dosing regimens of ABT-987: 500 mg q8h (Group I), 750 mg q8h
       (Group II), 375 mg q4h (Group III), or 875 mg q6h (Group IV). After
       discontinuing all antiviral therapy, patients enrolled in the study had
       a two week washout period followed by 8 weeks of treatment with ABT-987.
       A one week follow-up evaluation was done at the end of treatment after
       which patients were given the option of continued therapy with ABT-987.
       The antiviral activity was assessed by CD4 cell counts, p24 antigen
       levels, quantitative viral culture of plasma and peripheral blood
       mononuclear cells (PBMC) and quantitative RNA PCR in plasma. Viral and
       safety assessments were performed twice during the washout period,
       weekly during the first month of treatment and every two weeks during
       the second month of treatment. RESULTS: Mean viral titers decreased from
       baseline in Group II patients at 8 weeks (-1.6 log cellular and-1.7 log
       plasma) and in Group III patients at 2 weeks (-1.0 log plasma). Mean
       levels of p24 decreased from baseline in Group II at 2 weeks (-35%) and
       in Group IV at 1 week (-45%). Elevated transaminases resulted in
       premature discontinuation of one patient in Group II and in all patients
       in Group IV. CONCLUSION: Preliminary results demonstrate possible
       antiviral activity at the higher doses tested, however, these dosages
       were associated with elevated transaminase levels.
 DE    Adult  Human  HIV Infections/*DRUG THERAPY/IMMUNOLOGY/MICROBIOLOGY  HIV
       Protease Inhibitors/*ADMINISTRATION & DOSAGE/THERAPEUTIC USE  Leukocyte
       Count  T4 Lymphocytes  CLINICAL TRIAL  MEETING ABSTRACT  MULTICENTER
       STUDY

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