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LOW
IMMUNITY: ISOPRINOSINE |
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Department of Pharmacy
Practice, College of Pharmacy, University of Florida,
Gainesville.
The loss of immune competence that
occurs with aging may be responsible for increased
morbidity and mortality in elderly individuals. Pharmacologic
modulation of the immune response might reverse the
immunologic aberrations associated with aging. We,
therefore, investigated the effects of isoprinosine,
an immunoenhancing drug, on selected in vitro immune
responses in elderly subjects. Subjects studied were
65 years of age or older, and all had chronic diseases.
We chose this population since they were at greatest
risk for morbid events. Isoprinosine significantly
enhanced mitogen-stimulated mononuclear cell proliferation,
did not affect unstimulated cell growth, and needed
to be present for the entire culture period for maximum
effect. Isoprinosine is a potent in vitro immunoenhancing
agent in aged humans.
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Infektionsmedicinsk afdeling,
Hvidovre Hospital, Kobenhavn.
The safety and efficacy of isoprinosine
in HIV-infected individuals were assessed in a multicentre,
randomized, double-blind, 24-week study phase, followed
by an optional 24-week open treatment phase. The results
of the double-blind phase have been reported separately.
Of 866 HIV-seropositive individuals randomized, 832
were eligible for efficacy analysis. On completion
of the double-blind phase, 596 patients started open
treatment. All patients were evaluated with regard
to progression to AIDS. Within 48 weeks, 10/412 patients
(2.4%) assigned isoprinosine and 27/420 (6.4%) assigned
placebo progressed to AIDS (p = 0.005; odds ratio:
2.8, 95% CI: 1.3-6.2). Intention-to-treat analysis
showed identical results. No severe adverse reactions
or toxicities were observed. We conclude that HIV-infected
individuals without AIDS may be safely and effectively
treated with isoprinosine.
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reports a randomized, placebo-controlled trial of
inosine pranobex (isoprinosine), an experimental immunomodulating
agent. The study involved 866 persons infected with
HIV, the AIDS virus, in Sweden and Denmark. The report
suggests that patients in the isoprinosine arm of
the trial were significantly less likely to progress
to AIDS than those patients in the placebo arm of
the trial. According to this report, during the 24-week
trial, 17 patients in the placebo arm progressed to
AIDS as opposed to 2 patients in the isoprinosine
arm. Although the raw data from this study have not
been submitted for review to FDA by the drug's sponsor,
Newport Pharmaceuticals Inc. of Laguna Beach, Calif.,
the FDA's division of antiviral drug products has
reviewed the report. The division prepared a response
to the study report which also appears in the same
issue of the journal. The division's response expresses
a number of concerns about this study and other studies
conducted on isoprinosine, and states its belief that
more clinical investigation of this drug is needed
before its value to patients can be well enough evaluated
to decide whether, and on whom, it should be used.
-MORE- Page 2, isoprinosine, T90-26 Isoprinosine has
been under development as a treatment for HIV-infection
for approximately 5 years. Previous studies of isoprinosine's
effectiveness in delaying or preventing the onset
of AIDS in HIV-infected patients conducted in the
U.S. and other countries have not demonstrated that
the drug had any significant effect in slowing disease
progression in treated patients. For example, the
company reported in November of 1988 that a multicenter
trial of the drug involving 696 HIV-infected patients
in the U.S. and the U.K. showed no significant benefit
in those treated with isoprinosine as opposed to those
given placebo. The sponsor is currently reanalyzing
data from this study in order to evaluate why it produced
a different result than the Scandinavian trial. There
are also some issues concerning the design and analysis
of this latest Scandinavian study of isoprinosine.
For example, the classification system for determining
endpoints was changed during the course of the study
was one of a number of changes in the study's implementation
and analysis that may have affected the study results,
and may require additional, balanced assessment. An
editorial in the journal written by members of FDA's
division of anti-viral drug products also notes that
the 24 weeks of the trial is a relatively short study
period. FDA believes that additional clinical testing
should be conducted. These could incorporate the use
of pneumocystis prophylaxis and retroviral treatments
that have recently been developed as standard therapies
for HIV-individuals, in order to determine how isoprinosine
therapy, if proven effective, could be maximized in
today's current therapeutic scene.
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