Document 2847
 DOCN  M94A2847
 TI    A phase I/II open label combination study of the tolerability and
       activity of ddC and interferon alpha in patients with early symptomatic
       HIV-infection (ANRS protocol 016).
 DT    9412
 AU    Mouton Y; Goujard C; Raffi F; Seigneurin JM; Bilbault P; ANRS, Paris,
       France.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):211 (abstract no. PB0274). Unique
       Identifier : AIDSLINE ICA10/94369728
 AB    OBJECTIVES: Tolerability and antiviral activity of dideoxycytidine alone
       or in combination with two doses of interferon alpha based on laboratory
       markers (CD4, Ag P24, 82 microglobulin). To investigate the usefulness
       of quantitative plasma and cellular viraemia and quantitative RNA and
       DNA PCR. METHODS: In this open label multicenter phase I/II study 60
       HIV-infected patients with CD4 < or = 500 > or = 200 were randomized to
       receive ddC orally (0.75 mg twice daily) either alone or in combination
       with s.c. interferon alpha 2 A (1 M or 9 M thrice weekly) for 16 weeks.
       Patients had not previously received antiviral therapy but were at risk
       of disease progression (positive Ag P24 at baseline). RESULTS: 59
       patients were evaluated in 11 centers: 18 (ddC arm). 41 (ddC.IFN alpha
       combination arms). 21 patients received the low dose and 20 the high
       dose of IFN alpha. There were no differences in CDC classification
       between the two groups at baseline. However the CD4 cell count and Ag
       P24 titer showed more advanced disease in the ddC arm: median CD4 256
       cells/mm3 and median Ag p24 288 pg/ml compared to median CD4 346
       cells/mm3 and median Ag P24 155 pg/ml for the combination groups.
       Preliminary results over 16 weeks of treatment have not shown difference
       between the groups regarding the absolute change or % change from
       baseline for the CD4 count and for the change from baseline for the Ag
       P24 and the beta microglobulin but a 50 cells increase in ddC mono arm
       at week 4 was observed (see table below) and both groups showed
       substantial decline in P24. TABULAR DATA, SEE ABSTRACT VOLUME. Treatment
       was well tolerated for both monotherapy and combination (7 early
       discontinuations were observed). Preliminary data on the viral load on
       51 patients indicate an overall response showing clear antiviral
       activity. The complete results by therapy arm will be presented as well
       as results of susceptibility testing on viral isolates. CONCLUSIONS: The
       effects on the laboratory markers are difficult to interpret because of
       differences of baselines for the treatment groups even though the
       randomisation was respected. However this open label trial was also
       designed to further investigate quantitative viraemia and PCR the full
       analysis of which has been completed on most of the patients.
 DE    beta 2-Microglobulin/ANALYSIS  Biological Response
       Modifiers/ADMINISTRATION & DOSAGE/ADVERSE  EFFECTS/*THERAPEUTIC USE
       Combined Modality Therapy  Comparative Study  Human  HIV Core Protein
       p24/BLOOD  HIV Infections/DRUG THERAPY/*THERAPY  Interferon
       Alfa-2a/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/  *THERAPEUTIC USE
       Leukocyte Count  Treatment Outcome  T4 Lymphocytes  Viremia/DRUG
       THERAPY/THERAPY  Zalcitabine/ADMINISTRATION & DOSAGE/ADVERSE
       EFFECTS/*THERAPEUTIC  USE  CLINICAL TRIAL  CLINICAL TRIAL, PHASE I
       CLINICAL TRIAL, PHASE II  MEETING ABSTRACT  MULTICENTER STUDY
       RANDOMIZED CONTROLLED TRIAL

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