Adriana Weinberg, MD University of Colorado Denver

 Oseltamivir/Tamiflu  Zanamivir/Relenza  Amantadine/Symmetrel  Rimantadine/Flumadine  Other drugs less commonly used

 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?

 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

 Healthy individuals excrete seasonal influenza for up to 7 days without treatment and influenza A H1N 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

 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

 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 H1N  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)

 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

 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.

 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

 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

 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.

 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 H1N 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