H1N1 Swine Flu Update and CDC Interim Guidance for Clinicians Treating People with HIV

The novel H1N1 flu that originated in Mexico and first emerged in the U.S. 2 weeks ago continues to spread worldwide, but the severity of illness is less than initially feared, according to U.S. and international public health officials.

Authorities are now referring to the new strain as influenza A (H1N1) rather than swine flu, since it combines elements of swine, bird, and human influenza viruses. As a novel strain, most people do not have natural immunity against it. The H1N1 virus is susceptible to the flu drugs oseltamivir (Tamiflu) and zanamivir (Relenza), but resistant to amantadine (Symmetrel) and rimantadine (Flumadine). An effective vaccine is not yet available.

On April 30, the U.S. Centers for Disease Control and Prevention (CDC) issued "Interim Guidance -- HIV-Infected Adults and Adolescents: Considerations for Clinicians Regarding Swine-Origin Influenza A (H1N1) Virus." The recommendations, reprinted in full below, include information about clinical presentation, treatment and chemoprophylaxis, and other ways to reduce risk for HIV positive adults and adolescents.

Typically, people with weak immunity -- including young children, elderly people, and individuals with chronic illnesses -- are most susceptible to severe cases of influenza, although that pattern is not apparent so far in the current outbreak.

No adverse effects have been reported among HIV positive adults and adolescents taking oseltamivir or zanamivir, according to the CDC, and there are no known contraindications for co-administration of these medications with antiretroviral drugs.

The U.S. Food and Drug Administration (FDA) distributed a bulletin about the influenza outbreak to its HIV/AIDS listserv last week because of the large number of infectious disease professionals on the list. This bulletin, which includes information about Emergency Use Authorization for administration of oseltamivir to children, is also reprinted below.

"Any influenza carries potential risks for persons with HIV infection. Adults and adolescents with HIV infection, especially persons with low CD4 cell counts, are at higher risk for viral and bacterial lower respiratory tract infections, and for recurrent pneumonias," wrote FDA's Richard Klein and Kimberly Struble. "Because adults and adolescents infected with HIV experience more severe complications of seasonal influenza, it is reasonable to assume that they are also at higher risk for swine influenza complications."

Current Outbreak Status

According to the latest report from the CDC, as of Monday, May 4, there were 226 laboratory-confirmed cases of H1N1 influenza in the U.S., spread over 30 states, with the largest concentrations in California, New York, and Texas.

According to the World Health Organization (WHO), 20 countries have officially reported a total of 985 cases of H1N1 infection. The organization has declared a Phase 5 pandemic alert, indicating human-to-human spread of the virus into at least 2 countries in 1 region. Phase 6, the highest level, indicates community level outbreaks in multiple regions.

Importantly, the pandemic alert level indicates only the extent of an outbreak's spread, not the severity of illness. The severity of H1N1 appears no worse -- and perhaps considerably milder -- than normal seasonal influenza.

Seasonal outbreaks typically cause thousands of deaths in the U.S. each year. So far, only 1 person -- a young child in Texas -- has died of confirmed H1N1 influenza infection. As of May 4, Mexican health officials reported 22 fatalities linked to H1N1. Initially, the flu was thought to have a high mortality rate in Mexico, but it now appears that more people are infected than originally reported, therefore the proportion of deaths has fallen.

Flu Prevention

Public health officials advise that people experiencing flu symptoms should not go to school or work and should avoid public places; several cities have shut down schools after isolated cases were detected.

Symptoms of H1N1 flu include fever, fatigue, lethargy, lack of appetite, cough, runny nose, difficulty breathing, sore throat, body aches, and gastrointestinal symptoms such as nausea, vomiting, and diarrhea,

To date, the CDC has not recommended extraordinary precautions such as closing public gathering places, though it has advised against unnecessary travel to Mexico. The agency recommends the following steps to minimize flu transmission; additional measures may be appropriate for people with HIV, as indicated in the interim guidance.

• Cover your nose and mouth with a tissue when you cough or sneeze, and throw it in the trash after use.
• Wash your hands frequently with soap and water, or use an alcohol-based hand sanitizer.
• Avoid touching your eyes, nose, and mouth.
• If possible, avoid close contact with sick people.
• If you feel ill, stay home and avoid school, work, public transit, and other places where people gather.

Resources

CDC H1N1 Flu (Swine Flu) web site: www.cdc.gov/h1n1flu.

WHO Considerations on influenza A (H1N1) and HIV infection: www.who.int/hiv/mediacentre/influenza_hiv.pdf.

For regular flu updates on Twitter follow @CDCemergency and @AIDSgov.

CDC Interim Guidance -- HIV-Infected Adults and Adolescents: Considerations for Clinicians Regarding Swine-Origin Influenza A (H1N1) Virus (Updated May 3, 2009)

Background

Human infections with a swine-origin influenza A (H1N1) virus that is transmissible among humans were first identified in April 2009 with cases in the United States and Mexico. The epidemiology and clinical presentations of these infections are currently under investigation. There are insufficient data available at this point to determine who is at higher risk for complications of swine-origin influenza A (H1N1) virus infection. However, adults and adolescents with HIV infection, especially persons with low CD4 cell counts, are known to be at higher risk for viral and bacterial lower respiratory tract infections and for recurrent pneumonias.

Evidence that influenza can be more severe for HIV-infected adults and adolescents comes from studies among HIV-infected persons who had seasonal influenza; these data are limited. However, several studies have reported higher hospitalization rates, prolonged illness and increased mortality, especially among persons with AIDS. Thus, immune compromised persons, including HIV-infected adults and adolescents and especially persons with low CD4 cell counts or AIDS can experience more severe complications of seasonal influenza and it is possible that HIV-infected adults and adolescents are also at higher risk for swine-origin influenza complications.

Clinical Presentation

HIV-infected adults and adolescents with swine-origin influenza would be expected to present with typical acute respiratory illness (e.g., cough, sore throat, rhinorrhea) and fever or feverishness, headache, and muscle aches. For some HIV-infected persons, especially persons with low CD4 cell counts, illness might progress rapidly, and might be complicated by secondary bacterial infections including pneumonia. HIV-infected persons who have suspected swine-origin influenza A (H1N1) virus infection should be tested (see Guidance on Specimen Collection), and specimens from HIV-infected persons who have unsubtypeable influenza A virus infections should be sent to the state public health laboratory for additional testing to identify swine-origin influenza A (H1N1).

Persons with HIV infection should remain vigilant for the signs and symptoms of influenza, as outlined above. Persons with HIV infection who are concerned that they might be experiencing signs or symptoms of influenza infection, or who are concerned they might have been exposed to a confirmed, probable or suspected case of influenza infection, either seasonal influenza or swine-origin influenza A (H1N1), should consult their healthcare provider to assess the need for evaluation and for possible anti-influenza treatment or prophylaxis.

Treatment and Chemoprophylaxis

The currently circulating swine-origin influenza A (H1N1) virus is sensitive to the neuraminidase inhibitor antiviral medications zanamivir [Relenza] and oseltamivir [Tamiflu), but is resistant to the adamantane antiviral medications, amantadine and rimantadine.

HIV-infected adults and adolescents who meet current case-definitions for confirmed, probable or suspected swine-origin influenza A (H1N1) infection (see Guidance on Case Definitions) should receive empiric antiviral treatment. HIV-infected adults and adolescents who are close contacts of persons with probable or confirmed cases of swine-origin influenza A (H1N1) should receive antiviral chemoprophylaxis.

Antiviral chemoprophylaxis with either oseltamivir or zanamivir can be considered for HIV-infected persons who are household close contacts of a suspected case.

These recommendations for treatment and chemoprophylaxis are the same ones used for others who are at higher risk of complications from influenza. As is recommended for other persons who are treated, antiviral treatment with zanamivir or oseltamivir should be initiated as soon as possible after the onset of influenza symptoms, with benefits expected to be greatest if started within 48 hours of onset based on data from studies of seasonal influenza.

However, some data from studies on seasonal influenza indicate benefit for hospitalized patients even if treatment is started more than 48 hours after onset. Recommended duration of treatment is five days. Recommended duration of prophylaxis is 10 days after last exposure. Oseltamivir and zanamivir treatment and chemoprophylaxis regimens recommended for HIV-infected persons are the same as those recommended for adults who have seasonal influenza.

Clinicians should monitor treated patients closely and consider the need to extend therapy based on the course of illness. Recommendations for use of influenza antivirals for HIV-infected adults and adolescents might change as additional data on the benefits and risks of antiviral therapy in such persons become available.

No adverse effects have been reported among HIV-infected adults and adolescents who received oseltamivir or zanamivir. There are no known absolute contraindications for co-administration of oseltamivir or zanamivir with currently available antiretroviral medications.

Other Ways to Reduce Risk for HIV-infected Adults and Adolescents

There is no vaccine available yet to prevent swine-origin influenza A (H1N1).

The risk for swine-origin influenza A (H1N1) might be reduced by taking steps to limit possible exposures to persons with respiratory infections. These actions include frequent hand washing, covering coughs, and having ill persons stay home, except to seek medical care, and minimize contact with others in the household who may be ill with swine-origin influenza virus.

Additional measures that can limit transmission of a new influenza strain include voluntary home quarantine of members of households with confirmed or probable swine influenza cases, reduction of unnecessary social contacts, and avoidance whenever possible of crowded settings. If used correctly, facemasks and respirators may help reduce the risk of getting influenza, but they should be used along with other preventive measures, such as avoiding close contact and maintaining good hand hygiene.

A respirator that fits snugly on the face can filter out small particles that can be inhaled around the edges of a facemask, but compared with a facemask it is harder to breathe through a respirator for long periods of time. Interim guidance regarding means to decrease the risk of getting swine-origin influenza virus is available. These guidances will be updated as more information becomes available, including information on the risk of swine-origin influenza-related complications among HIV-infected adults and adolescents.

Patients should be reminded of the importance of maintaining their health as a means of reducing their risk of infection with influenza and improving their immune system’s ability to fight an infection should it occur. In particular, patients who are currently taking antiretrovirals or antimicrobial prophylaxis against opportunistic infections should be reminded of the importance of adhering to their prescribed treatment [Emphasis added -- Ed].

FDA Issues Bulletin to HIV/AIDS List/Serve Regarding “Swine Flu” (H1N1)

Although normally this list is used solely to distribute information specifically related to HIV/AIDS, the FDA decided to send this message regarding influenza because of the number of infectious disease professionals subscribed to the HIV/AIDS list/serve for whom this information is important.

On April 26, the Acting Secretary of HHS declared a public health emergency related to the current outbreak of "swine flu" (now designated "novel 2009 H1N1"). In response to this public health emergency, the CDC requested Emergency Use Authorization (EUA) for the use of Tamiflu and Relenza for treatment and prophylaxis of influenza for broader populations than are currently included in the product labeling, including pediatric populations, and others who fall outside of the indicated uses.

Influenza viruses cause serious, sometimes fatal, disease in immuno-compromised patients, including HIV infected infants, toddlers, and young children.

Currently, Relenza is approved to treat acute uncomplicated illnesses due to influenza in adults and children 7 years and older who have been symptomatic for less than two days, and for the prevention of influenza in adults and children 5 years and older. Tamiflu is approved for the treatment and prevention of influenza in patients 1 year and older.

The EUAs allow for Tamiflu also to be used to treat and prevent influenza in children under 1 year, and to provide alternative dosing recommendations for children older than 1 year. In addition, under the EUAs, both medications may be distributed to large segments of the population without complying with the label requirements otherwise applicable to dispensed drugs, and accompanied by written information pertaining to the emergency use. They may also be distributed by a broader range of health care workers, including some public health officials and volunteers, in accordance with applicable state and local laws and/or public health emergency responses.

These temporary extensions of the indication, which will terminate when the emergency no longer exists, are summarized below:

1. Use of Tamiflu for treatment and prophylaxis of influenza in infants < 1 year of age.Tamiflu is currently approved for use in patients 1 year of age and older. New dosing recommendations in infants < 1 year were based on expedited review of safety and pharmacokinetic data submitted by Roche and the Collaborative Antiviral Study Group of NIAID/NIH. In addition, age-based dose recommendations in older children were included in these new recommendations. These EUA recommendations are intended for use with Tamiflu for Oral Suspension and are shown here:

Expanded EUA Tamiflu Dose Recommendations for Treatment of Influenza in Pediatric Patients
Body Weight (kg)	Body Weight (lbs)	Dose by Age	Recommended Treatment Dose for 5 Days
>40 kg	>88 lbs	≥ 10 years	75 mg twice daily
>23 kg to 40 kg	>51 lbs to 88 lbs	6-9 years	60 mg twice daily
>15 kg to 23 kg	>33 lbs to 51 lbs	3-5 years	45 mg twice daily
≤15 kg	≤33 lbs	1-2 year	30 mg twice daily
Dosing for infants younger than 1 year not based on weight		6-11 months	25 mg twice daily
		3-5 months	20 mg twice daily
		< 3 months	12 mg twice daily

The Tamiflu Oral Suspension bottle comes with a dispenser marked for 30, 45, or 60 mg. For children who weigh more than 40 kg (or 88 lbs) or adults who can't swallow capsules, you will need to measure out a dose of 30 mg plus another dose of 45 mg. For infants less than 1 year old, a different measuring device must be used that will dispense 2 mL (about 25 mg), 1.6 mL (about 20 mg) or 1 mL (12 mg).

Doses for prevention of the novel 2009 H1N1 are the same for each weight group, but doses are administered only once per day rather than twice. Prevention dosages should be taken for 10 days following close contact with an infected person or during a community outbreak.

2. Use of Tamiflu and Relenza in patients not included in the current labeling. These drugs are currently indicated for use in patients with acute, uncomplicated influenza who have had symptoms for < 48 hours.

The EUA allows for use of Tamiflu and Relenza in patients who have more severe influenza disease or who have been ill for longer than 48 hours based on limited published data and the understanding that the novel 2009 H1N1 may have different presentations. Depending on available products and susceptibility data, clinicians may wish to make individual risk-benefit assessments regarding the appropriate use of the products.

More detailed information about Influenza Antiviral Drugs is available on the FDA web site.

The Tamiflu Fact Sheet For Health Care Providers contains information specific to the expanded pediatric dosing recommendations for Tamiflu.

5/05/09

Sources

U.S.Centers for Disease Control and Prevention (CDC). Interim Guidance -- HIV-infected Adults and Adolescents: Considerations for Clinicians Regarding Swine-origin Influenza A (H1N1) Virus. April 30-May 3, 2009. www.cdc.gov/h1n1flu/guidance_HIV.htm.

R Klein and K Struble (U.S. Food and Drug Administration (FDA)). Bulletin to HIV/AIDS List/Serve. April 30, 2009.

World Health Organization. Considerations on influenza A(H1N1) and HIV infection (undated). www.who.int/hiv/mediacentre/influenza_hiv.pdf.