Document 0160
 DOCN  M94A0160
 TI    A phase II study of effect of addition of trichosanthin to zidovudine in
       patients with HIV disease and failing antiretroviral agents.
 DT    9412
 AU    Byers VS; Levin AS; Malvino A; Waites L; Robins RA; Baldwin RW;
       Immunology, Inc., San Francisco, California 94108.
 SO    AIDS Res Hum Retroviruses. 1994 Apr;10(4):413-20. Unique Identifier :
       AIDSLINE MED/94347466
 AB    Patients infected with HIV, including those with AIDS-related complex
       and AIDS, and failing treatment with antiretroviral agents such as
       zidovudine, have been evaluated following addition of trichosanthin to
       the antiretroviral agent regimen. This ribosomal inhibitory protein is
       specifically cytotoxic for HIV-infected macrophages and lymphocytes.
       Ninety-three patients were treated with trichosanthin, using a schedule
       of weekly, then monthly, intravenous injections of 1.2 mg of drug in
       combination with antiretroviral agents, usually zidovudine. Side effects
       included myalgias, fevers, mild elevation in liver function tests, and
       mild-moderate anaphylactic reactions, which respond well to therapy with
       steroids and/or benedryl. Reversible mental status changes were noted in
       two patients, both receiving concomitant therapy with ddI. Clinical
       responses to trichosanthin treatment were monitored primarily by changes
       in laboratory parameters, particularly levels of CD4+ T lymphocytes. In
       the total population evaluated for efficacy (85 patients) there was a
       significant increase in CD4+ cell levels after initiation of
       trichosanthin therapy. A second analysis performed on 72 patients
       measured the rate of change of CD4+ cells during therapy, using an area
       under the curve analysis. During therapy there was a median increase of
       1.2 cells/mm3/month. In patients in the top 25th percentile, this
       increase was greater than 8.4 cells/mm3/month. In 59 of the 72 patients,
       responses could also be monitored by comparing the rate of loss of CD4+
       cell levels on antiretroviral agents (zidovudine or ddI) alone, during
       the year prior to initiation of trichosanthin, to the rate of change
       when trichosanthin was added to the treatment regimen. During the period
       before trichosanthin treatment (311 +/- 11.7 days) the median loss of
       CD4+ cells was 6.91 cells/mm3/month. Addition of trichosanthin to the
       treatment regimen resulted in a median gain of 1.1 CD4+ cells/mm3/month.
 DE    Adolescence  Adult  Aged  Didanosine/ADMINISTRATION & DOSAGE  Drug
       Therapy, Combination  Female  Human  HIV Infections/BLOOD/*DRUG
       THERAPY/IMMUNOLOGY  Leukocyte Count  Liver/DRUG EFFECTS  Male  Middle
       Age  Trichosanthin/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS  T4
       Lymphocytes  Zidovudine/*ADMINISTRATION & DOSAGE  CLINICAL TRIAL
       CLINICAL TRIAL, PHASE II  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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