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Adriana Weinberg, MD
University of Colorado Denver
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Oseltamivir/Tamiflu
Zanamivir/Relenza
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Amantadine/Symmetrel
Rimantadine/Flumadine
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Other drugs less commonly used
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HIV-infected patients receive the same drug
regimens as healthy individuals, most
commonly oseltamivir.
Are the doses adequate?
Is the duration of treatment adequate?
Are there any interactions between antiinfluenza medication and antiretrovirals?
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Clinical efficacy trials
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Virologic efficacy trials
◦ How much faster treated participants recover from
influenza
◦ Very informative
◦ Require large numbers of participants
◦ Resolution of infection in response to treatment.
◦ Collect daily respiratory material from patients on
treatment and estimate after how many days they
stop excreting influenza
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Healthy individuals excrete seasonal
influenza for up to 7 days without
treatment and influenza A H1N1 2009 for
an average of 6 days on treatment
Immunosuppressed patients may excrete
seasonal influenza for weeks and months in
spite of treatment
Resistance to antivirals develops rarely in
healthy hosts and much more commonly in
immunosuppressed hosts
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Seasonal influenza A H1N1 and H3N2 were
susceptible to all classes of drugs 5 years ago
Seasonal influenza A H1N1 developed 100%
resistance to oseltamivir/tamiflu in the last 2
years
Seasonal influenza A H3N2 developed almost
100% resistance to amantadine/symmetrel
and rimantadine/flumadine in the last 4 years
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Higher doses of oseltamivir/tamiflu
◦ There is no evidence that higher doses work better,
but higher doses are used by some experts to treat
severe cases of influenza A H1N1 2009
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Combination of different anti-influenza
antivirals
◦ Several animal models of influenza infection support
the benefit of combination therapy
◦ It is currently used for influenza A H5N1 (bird flu)
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Prolonged therapy against influenza may be
warranted if we demonstrate that HIVinfected hosts have longer disease and that
they shed susceptible virus while on
treatment
Interactions with antiretrovirals: unlikely
based on the metabolism of the drugs, but
need to be studied
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Approx. 30% of fatal cases in the current
pandemic are due to bacterial complications
of influenza.
CDC recommends immunization of highly
susceptible hosts against pneumococcus, one
of the most common causes of pneumonia
and the only one for which a vaccine is
available.
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In general, HIV-infected individuals respond
poorly to vaccines
2 anti-pneumococcal vaccines are available:
polysaccharide and conjugate vaccines
The polysaccharide vaccine is
recommended for adults including those
with HIV infection
◦ Responses of HIV-infected individuals to this
vaccine are very low

Conjugate vaccine seems to raise higher
titers of antibodies in HIV-infected hosts,
but very few studies were done
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HIV-infected hosts make antibodies in
response to seasonal influenza vaccines, but
in lower titers
Most studies in adults and our own studies in
children compared the responses of the HIVinfected hosts with historical controls
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Seasonal influenza vaccine protects to some
extent HIV-infected adults against influenza
◦ 4 studies in adults

Our own pediatric study confirmed the
relationship between antibody levels and
protection against infection with a live
attenuated influenza virus that is used in
FluMist
There is none.
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HIV-infected hosts with preserved immune
system do not seem to develop very severe
disease with influenza, including the
pandemic strain
They can be protected against influenza with
the use of vaccines

Treatment of influenza A H1N1 2009 and
seasonal influenza in HIV-infected hosts
◦ Duration, doses, interactions with antiretrovirals
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Duration of shedding of influenza viruses in
HIV-infected patients as it also affects their
contacts
Development of antiviral resistance of
influenza when HIV-infected patients are
treated