Adriana Weinberg, MDUniversity 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 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

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 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