Document 2853
 DOCN  M94A2853
 TI    Safety and efficacy of ZDV addition to 3TC monotherapy.
 DT    9412
 AU    van Leeuwen R; Boucher C; Reiss P; Schuurman R; Nijhuis M; Danner S;
       National AIDS Therapy Evaluation Centre, University of Amsterdam,; The
       Netherlands.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):21 (abstract no. 057B). Unique
       Identifier : AIDSLINE ICA10/94369722
 AB    OBJECTIVE: Lamivudine (3TC, (-) enantiomer of 2'-3'-thiacytidine) and
       zidovudine (zdv) exhibit in vitro synergistic antiviral activity.
       Moreover, an RT mutation encoding for 3TC resistance (Met184-->Val),
       results in suppression of resistance against zdv in vitro. In a phase
       I/II study to the effects of monotherapy with 3TC in CDC stage II/III or
       IV-C2 patients the Val184 mutation was detected after 1-12 weeks of
       therapy. In this study transient increases in CD4 counts and sustained
       reductions in p24 antigen have been observed. We report on the effects
       of zdv addition to 2 different dosages of 3TC. METHODS: Thirty patients
       were part of this multi-centre, open-label, non-randomised study with 2
       dosages of 3TC: 100mg bid (arm A, 16 pts) and 300mg bid (arm B, 14 pts).
       Zdv 200mg tid was added after > or = 24 weeks (in a majority > or = 52
       weeks) 3TC monotherapy, or in case of clinical and/or immunological
       deterioration. Baseline values were defined as the mean of 2 pre-entry
       values (week -4 & 0). This is an interim analysis of the first 36 weeks.
       RESULTS: The median baseline CD4 count was 113 (5-95 percentile: 10-315)
       cells/mm3; median CD4 percent 11 (1-27)%. 11 pts were p24 antigen
       positive; 6 patients had AIDS at the start of the study. The baseline
       characteristics of arm A and B were not statistically different. The
       most frequently reported (mild) adverse experiences: fatigue (29 pts),
       indigestion (25), headache (18), diarrhoea (16), myalgia/arthralgia
       (11), abdominal pain (10), night sweats (10), itching (10),
       sleeplessness (9), fever (8), anaemia (8), and neutropenia (8). No
       differences were detected in the number of adverse events and dose
       adjustments between arm A and B. Median % change from baseline levels
       for absolute CD4 cell counts and p24 antigen levels are depicted in the
       Figure. Analysis of these and other surrogate markers did not reveal
       important differences between arm A and B. CONCLUSION: No unexpected
       adverse experiences were reported. CD4+ cell counts increased, and
       remained above baseline values at 7/8 timepoints in the study, p24
       antigen levels were > or = 65% below baseline throughout the study. No
       apparent differences were detected in tolerance or efficacy of 200 or
       600 mg 3TC. Extended follow-up, as well as data on plasma HIV-1 RNA load
       and resistance will be presented. TABULAR DATA, SEE ABSTRACT VOLUME.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY  Antiviral
       Agents/*ADMINISTRATION & DOSAGE  Drug Therapy, Combination  Human  HIV
       Core Protein p24/ISOLATION & PURIF  Leukocyte Count  T4 Lymphocytes
       Zalcitabine/*ANALOGS & DERIVATIVES/ADMINISTRATION & DOSAGE/  ADVERSE
       EFFECTS  Zidovudine/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS  CLINICAL
       TRIAL  CLINICAL TRIAL, PHASE I  CLINICAL TRIAL, PHASE II  MEETING
       ABSTRACT  MULTICENTER STUDY

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).