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The International AIDS Society–USA
The 2009-2010 H1N1 Pandemic:The 2009-2010 H1N1 Pandemic:Impact on HIVImpact on HIV
Anne Moscona, MDProfessor of Pediatrics and of Microbiology
and ImmunologyWeill Medical College of Cornell University
Met requirements for an Influenza PandemicMet requirements for an Influenza Pandemic
Isolation from humans of an influenza A virus with novel hemagglutinin (or hemagglutinin and neuraminidase) genes.
Susceptibility (lack of antibody) to this novel virus in a large proportion of the population.
Demonstrated ability of the virus to cause disease & spread from person-to-person (sustained chains of transmission, community-wide outbreaks).
Isolation from humans of an influenza A virus with novel hemagglutinin (or hemagglutinin and neuraminidase) genes.
Susceptibility (lack of antibody) to this novel virus in a large proportion of the population.
Demonstrated ability of the virus to cause disease & spread from person-to-person (sustained chains of transmission, community-wide outbreaks).
Current picture (November) of 2009 H1N1:Current picture (November) of 2009 H1N1:
Transmissible between people at rate similar to previous pandemics, even in warm weather
Confirmed cases are concentrated in groups under 24 years of age
Almost all severe cases are in people under 65: 83% of deaths, 71% of hospitalization in ages 5 to 64…in contrast to seasonal flu where 90% of deaths are in people >65
Transmissible between people at rate similar to previous pandemics, even in warm weather
Confirmed cases are concentrated in groups under 24 years of age
Almost all severe cases are in people under 65: 83% of deaths, 71% of hospitalization in ages 5 to 64…in contrast to seasonal flu where 90% of deaths are in people >65
Current picture of 2009 H1N1:Current picture of 2009 H1N1:
Certain underlying medical conditions confer elevated risk of severe outcomes:
—neurological disorder---pregnancy
One-third of fatal cases + one-fifth of hospitalizations have been in persons with neurological (neurocognitive, neuromuscular, seizure) disorders
Pregnant women (1% of population) = 8 % of deaths
Immunodeficiencies, asthma, diabetes, chronic obstructive pulmonary disease (COPD), also seem to be associated with severe outcomes.
Certain underlying medical conditions confer elevated risk of severe outcomes:
—neurological disorder---pregnancy
One-third of fatal cases + one-fifth of hospitalizations have been in persons with neurological (neurocognitive, neuromuscular, seizure) disorders
Pregnant women (1% of population) = 8 % of deaths
Immunodeficiencies, asthma, diabetes, chronic obstructive pulmonary disease (COPD), also seem to be associated with severe outcomes.
Current picture of 2009 H1N1:Current picture of 2009 H1N1:
In HIV-infected patients with low CD4 cell counts,
-illness may progress rapidly
-may be complicated by secondary bacterial infection
Clinical judgment / local surveillance data are key
In HIV-infected patients with low CD4 cell counts,
-illness may progress rapidly
-may be complicated by secondary bacterial infection
Clinical judgment / local surveillance data are key
Atypical featuresAtypical features
Transmissible in warm weather vs. seasonal flu, whose transmission halts as the weather warms (hypothesis: aerosol in winter, contact in summer)
Infects the gastrointestinal tract in one-third of serious cases
Transmissible in warm weather vs. seasonal flu, whose transmission halts as the weather warms (hypothesis: aerosol in winter, contact in summer)
Infects the gastrointestinal tract in one-third of serious cases
Virulence / pathogenicityVirulence / pathogenicity
Case-fatality ratio (proportion of infected individuals who die as a result of the infection) appears to be similar to seasonal influenza
~0.1 to 0.3 % of medically attended cases
~0.05 to 0.2 % of all symptomatic cass
BUT these numbers are highly uncertain
Case-fatality ratio (proportion of infected individuals who die as a result of the infection) appears to be similar to seasonal influenza
~0.1 to 0.3 % of medically attended cases
~0.05 to 0.2 % of all symptomatic cass
BUT these numbers are highly uncertain
Four elements of response:Four elements of response:
--vaccines
--anti-viral drugs
--medical care
--non-medical interventions that diminish virus spread
--vaccines
--anti-viral drugs
--medical care
--non-medical interventions that diminish virus spread
Who should be vaccinated vs seasonal influenza?
Who should be vaccinated vs seasonal influenza?
Adults >50 yrs
Children ages 6 months to 18 years
Pregnant women
Adults with:Immunodeficiency, heart or lung disease
Metabolic, renal, neuromuscular disease
Persons who live with or care for high-risk individuals
All health care workers
Adults >50 yrs
Children ages 6 months to 18 years
Pregnant women
Adults with:Immunodeficiency, heart or lung disease
Metabolic, renal, neuromuscular disease
Persons who live with or care for high-risk individuals
All health care workers
Options for vaccines for 2009 H1N1Options for vaccines for 2009 H1N1
Live attenuated vaccine: reassortant viruses prepared with “master” attenuated strain used in “FluMist”
(ages 2-49, non-pregnant, no underlying lung disease, no immunodeficiency)
Inactivated vaccine: reassortant viruses containing HA and NA from pandemic strain
(All - 6 months and up)
Live attenuated vaccine: reassortant viruses prepared with “master” attenuated strain used in “FluMist”
(ages 2-49, non-pregnant, no underlying lung disease, no immunodeficiency)
Inactivated vaccine: reassortant viruses containing HA and NA from pandemic strain
(All - 6 months and up)
Who should receive 2009 H1N1 vaccine?Initial target groups for vaccine:
Who should receive 2009 H1N1 vaccine?Initial target groups for vaccine:
All health care workers and any other individuals who work in hospitals should be vaccinated
Pregnant women
People caring for (or living with) infants under 6 months
People 6 months – 24 years (esp. 6 months – 4 years)
25 years- 64 years with risk factors for higher risk of medical complications from influenza, including HIV infection, are an initial target group
All health care workers and any other individuals who work in hospitals should be vaccinated
Pregnant women
People caring for (or living with) infants under 6 months
People 6 months – 24 years (esp. 6 months – 4 years)
25 years- 64 years with risk factors for higher risk of medical complications from influenza, including HIV infection, are an initial target group
Two classes of influenza antiviral drugs: Adamantanes and neuraminidase inhibitors
Two classes of influenza antiviral drugs: Adamantanes and neuraminidase inhibitors
Adamantanes = M2 inhibitors
Interfere with viral uncoating inside the cell
Only effective against influenza A
Associated with severe toxicities
Rapid emergence of drug-resistant variants during treatment
Viral resistance develops in up to 30% of patients as soon as 3 days after starting a course of amantadine or rimantidine treatment……drugs useless vs. H3N2 in 2005-6 (91% resistance)
Adamantanes = M2 inhibitors
Interfere with viral uncoating inside the cell
Only effective against influenza A
Associated with severe toxicities
Rapid emergence of drug-resistant variants during treatment
Viral resistance develops in up to 30% of patients as soon as 3 days after starting a course of amantadine or rimantidine treatment……drugs useless vs. H3N2 in 2005-6 (91% resistance)
Neuraminidase inhibitors Neuraminidase inhibitors
Zanamivir and oseltamivir
Interfere with the viral enzyme that releases newly formed virus from an infected cell
Prevent the spread of virus from cell to cell
Effective against both influenza A and B
Very little toxicity
Resistance has become a problem for oseltamivir.
Zanamivir and oseltamivir
Interfere with the viral enzyme that releases newly formed virus from an infected cell
Prevent the spread of virus from cell to cell
Effective against both influenza A and B
Very little toxicity
Resistance has become a problem for oseltamivir.
ZanamivirZanamivir
Zanamivir is not orally bioavailable
Dry powder for inhalation, delivered directly to the site of infection in the respiratory tract via a diskhaler
Inhaled zanamivir is highly concentrated in the respiratory tract.
Only 5- 15% of the dose is absorbed and excreted in the urine
Inhibitory effect starts within 10 seconds
Zanamivir is not orally bioavailable
Dry powder for inhalation, delivered directly to the site of infection in the respiratory tract via a diskhaler
Inhaled zanamivir is highly concentrated in the respiratory tract.
Only 5- 15% of the dose is absorbed and excreted in the urine
Inhibitory effect starts within 10 seconds
OseltamivirOseltamivir
Oseltamivir is available in tablet or liquid forms
Twice daily administration
Readily absorbed from the GI tract, converted by hepatic esterases to the active form, oseltamivir carboxylate, widely distributed in the body
Half-life is 6-10 hours - eliminated primarily by renal excretion
Due to the high levels of drug in plasma, oseltamivir can act outside the respiratory tract
Oseltamivir is available in tablet or liquid forms
Twice daily administration
Readily absorbed from the GI tract, converted by hepatic esterases to the active form, oseltamivir carboxylate, widely distributed in the body
Half-life is 6-10 hours - eliminated primarily by renal excretion
Due to the high levels of drug in plasma, oseltamivir can act outside the respiratory tract
Consideration of antiviral treatment or chemoprophylaxis in HIV infection
Consideration of antiviral treatment or chemoprophylaxis in HIV infection
Clinical judgment:HIV-infected individuals are a high-priority group
for prevention and treatment of 2009 H1N1 influenza
Vaccinate
Treat early (despite lack of timely or accurate viral diagnosis)
Attention to surveillance
Clinical judgment:HIV-infected individuals are a high-priority group
for prevention and treatment of 2009 H1N1 influenza
Vaccinate
Treat early (despite lack of timely or accurate viral diagnosis)
Attention to surveillance
