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Influenza A H1N1 2009 and HIV: Questions raised by the convergence of these pandemics. Adriana Weinberg, MD University of Colorado Denver. Treatment of HIV-infected patients with influenza A H1N1 2009. Drugs available for treatment of influenza. Oseltamivir/Tamiflu Zanamivir/Relenza
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Influenza A H1N1 2009 and HIV: Questions raised by the convergence of these pandemics Adriana Weinberg, MD University of Colorado Denver
Treatment of HIV-infected patients with influenza A H1N1 2009
Drugs available for treatment of influenza • Oseltamivir/Tamiflu • Zanamivir/Relenza • Amantadine/Symmetrel • Rimantadine/Flumadine • Other drugs less commonly used
Treatment issues specific to HIV-infected patients • 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 anti-influenza medication and antiretrovirals?
What studies are needed and feasible? • Clinical efficacy trials • How much faster treated participants recover from influenza • Very informative • Require large numbers of participants • Virologic efficacy trials • 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
What is known about influenza shedding? • 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
Resistance of seasonal influenza A to antivirals • 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
Are there more potent treatment options? • 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 • 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)
Other treatment issues • Prolonged therapy against influenza may be warranted if we demonstrate that HIV-infected 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
Bacterial pneumonia as a complication of influenza • 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.
Anti-pneumococcal vaccines in HIV-infected hosts • 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
How do HIV-infected patients respond to influenza vaccines? • 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 HIV-infected hosts with historical controls
Influenza antibodies signal protection of HIV-infected hosts • 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
Is there any danger that HIV and influenza A H1N1 2009 may recombine/fuse and create a new monster virus? There is none.
Summary of the positive findings • 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
Summary of areas that need to be further studied • Treatment of influenza A H1N1 2009 and seasonal influenza in HIV-infected hosts • Duration, doses, interactions with antiretrovirals • 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