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 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
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 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)
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
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 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