Forum: Seasonal and H1N1 Swine Flu Are Risks for People with HIV, but Vaccines Are Scarce

		SUMMARY: HIV positive people -- especially those with a low CD4 cell count -- should get vaccinated against the flu, a panel of experts agreed at a November 10 forum in San Francisco on "Surviving the Flu Epidemic." However, the clinicians reported that they did not yet have a supply of the 2009 H1N1 swine flu vaccine, and local stocks of seasonal flu vaccine have run out since the government directed manufactures to shift to H1N1 vaccine production. In the meantime, they suggested, it would be prudent to have the flu drug oseltamivir (Tamiflu) on hand.

By Liz Highleyman

The forum, sponsored by the Conant Foundation and Project Inform, aimed to fill in some information gaps for people with HIV as they consider how to protect themselves as the flu season gets underway.

While annual seasonal flu typically hits around late December and lasts about 8 weeks, the current outbreak of novel 2009 H1N1 influenza A had an unusual springtime debut and did not disappear after a few months; in fact, the pandemic worsened when children returned to school in the fall.

Lawrence Drew, MD, director of the University of California at San Francisco (UCSF) Clinical Virology Laboratory opened with a discussion of the characteristics of the influenza virus and a brief history of flu pandemics.

(L to R: Jay Lalezari, Alan McCord, Lawrence Drew, Michael Harbour, Marcus Conant)

The "H" and "N" in flu designations refer to proteins that enable the virus to enter and exit host cells. Influenza viruses mutate constantly, usually making minor changes. But when the H and N proteins undergo significant change, the immune system can no longer recognize and respond to the virus.

Different influenza viruses are adapted to live and reproduce in particular animal species. To become a human epidemic, a specific flu not only must cross over from another species (such as pigs), but also must develop the ability to be transmitted between people. The Asian avian (bird) flu that made headlines a few years ago was highly lethal, but so far has not evolved the ability to spread from person to person.

Before about 1900, Dr. Drew said, the most common flu type was H3N8, which is now rarely seen. In 1918, a new H1N1 virus appeared, mostly likely crossing to humans from swine. The resulting Spanish flu pandemic killed an estimated 40-50 million people worldwide, but those who survived developed immunity. In 1957, a new H2N2 strain emerged, causing the Asian flu pandemic. After this came an outbreak of H3N2 flu that was not particularly severe; this remained the dominant strain, coexisting with a new H1N1 variant that emerged in 1979.

The novel 2009 H1N1 virus -- which was first reported in Mexico and Southern California in April -- is now the dominant flu strain in the world, according to Dr. Drew. It is different enough from the 1979 H1N1 that people exposed to that virus are not immune to the new one. But people born before 1957 may have developed enough immunity to the 1918 H1N1 strain to offer some degree of protection against the 2009 version.

So far, the H1N1 flu has not proven unusually virulent, with a fatality rate similar to, or even slightly below, that of seasonal flu, which typically kills an estimated 36,000 people annually, according to the Centers for Disease Control and Prevention (CDC).

However, experts are concerned because 2009 H1N1 has shown a propensity to kill young adults not just infants and the elderly -- also a characteristic of the deadly 1918 flu. The new flu is also unusual in its ability to maintain itself in the population, rather than burning out after several weeks and disappearing like seasonal flu.

Flu Vaccines

In August, the CDC issued a list of priority groups to receive the H1N1 vaccine. These include pregnant women, caretakers of infants younger than 6 months old, and healthcare personnel who have direct contact with patients.

Next on the priority list are children and young adults aged 6 months to 24 years and adults between the ages of 25 and 64 with chronic health disorders or compromised immunity. To date, most H1N1-related hospitalizations and death have occurred in pregnant women, diabetics, and obese people; patients taking immunosuppressive drugs after a transplant are also considered high risk. While older people are usually a flu vaccine priority, in the case of 2009 H1N1 they are the most likely to retain some immunity from exposure to a similar past flu.

While immunocompromised individuals are on the priority list, so far there has not been evidence that HIV positive people are more likely to experience flu-related complications or fatalities.

However, people with HIV do appear to remain sick longer, said Jay Lalezari, MD, Assistant Clinical Professor of Medicine at UCSF and director of Quest Clinical Research. He explained that the CD4 count at which the risk of flu complications rises is "poorly defined," but he guessed that those with fewer than 500 cells/mm3 should take precautions.

The usual advice is that people with compromised immunity -- including HIV positive people and pregnant women -- should receive the injected H1N1 vaccine, which contains killed virus. The nasal vaccine contains attenuated or weakened virus that can cause illness in people with poor immunity.

But the panel agreed that if the injected vaccine is not available, HIV positive people should get the nasal vaccine, which would likely only cause mild flu-like illness, especially in people on antiretroviral therapy who have a relatively high CD4 cell count.

This all may be moot, however, since vaccines for both H1N1 and seasonal flu are hard to come by. According to Dr. Lalezari, the San Francisco Department of Public Health is out of H1N1 vaccine. New supplies are supposed to go to primary care providers, but he hasn't received it yet.

"We were promised vaccine last month," said Conant Foundation director Marcus Conant, MD, who moderated the forum. "Now they're saying December or January."

Dr. Conant explained that the federal government instructed vaccine manufacturers to stop making seasonal flu vaccine and switch to H1N1 vaccine production. As a result, seasonal flu vaccine has run out in the Bay Area, and those who did not get their shots already probably will not be able do so for the remainder of this year's flu season.

HIV positive people should also receive the Pneumovax vaccine to prevent bacterial pneumonia, according to Dr. Conant. "The risk is that if you get the flu, you'll get pneumonia, and the pneumonia is what will kill you," he said.

The Pneumovax vaccine provides protection against multiple strains of Streptococcus pneumoniae. Since new strains are added as the bacteria evolve, Dr. Conant added that HIV positive people who have not received the vaccine in the past 5 years should get it again (for the HIV negative general population, the recommendation is every 10 years starting at age 65).

Other important prevention measures, the panel said, include frequent hand washing, coughing into one's sleeve, avoiding unnecessary travel, and staying away from work, school, or other public gatherings while ill.

Asked if there were any specific recommendations for sex clubs, Dr. Conant replied, "If you're sick, stay home."

Antiviral Therapy

In the absence of a vaccine, antiviral drugs are the main line of defense against influenza.

Asked how to distinguish a flu from a cold, Michael Harbour, MD, Clinical Assistant Professor of Medicine at Stanford and HIV Medical Director for Merck, explained that people with the flu usually have a fever of at least 100 degrees F, along with respiratory symptoms that may include sore throat and cough. These may be accompanied by aches, malaise, and fatigue. A cough and nasal congestion without a fever or "flu-like" feeling is more likely to indicate a cold.

The new H1N1 influenza is generally susceptible to oseltamivir, though resistant strains have been found. However, it is resistant to another flu drug, amantadine (Symmetrel), that is effective against some seasonal flu. People who come down with the flu today and need treatment should receive oseltamivir. Dr. Drew noted that laboratory testing to confirm 2009 H1N1 is no longer recommended, as this is now the dominant flu type and the test is not very accurate.

It is commonly recommended that flu treatment should start within 48 hours to be effective, but Dr. Drew said that even beyond this time limit, HIV positive people should consider therapy to reduce the duration of illness.

Oseltamivir may also be taken preventively if a person is exposed to influenza. With seasonal flu, prophylactic treatment is discontinued when the flu season ends, but the stopping point is less clear with an ongoing outbreak like 2009 H1N1, which has remained at a fairly consistent level since the spring. But, according to Dr. Drew, "if you get through 10 days of exposure without getting the flu, more than likely you're not going to get it," and can stop therapy.

Panel members agreed that it would be a good idea for HIV positive people to ask their doctors for a prescription for oseltamivir to have on hand, especially since the drug works best when started as soon as possible after symptoms begin and because supplies may run low.

Regarding expiration dates, Dr. Harbour explained that anti-flu medications do not lose their efficacy overnight, and that expired drugs may be used if that's all that is available. "If the expiration date was yesterday, don't hesitate," he said.

HIV Positive Flu Treatment Study

Dr. Lalezari is currently recruiting participants for a study of flu treatment in people with HIV. The study will evaluate a 3-drug "cocktail" including oseltamivir, amantadine, and ribavirin (produced by Adamas Pharmaceuticals). Since it is not always evident what type of influenza an individual has, the combination could provide better coverage, Dr. Lalezari explained.

The study will include HIV positive people with a CD4 cell count below 500 cells/mm3. Participants will be randomly assigned to receive either the fixed-dose triple combination or standard therapy. They will be treated at home and will receive compensation for their time.

Prospective participants are urged to call the study's flu hotline at 888-544-8358 (888-5-HIV-FLU) if they experience flu symptoms including a fever of 100 degrees F or higher. Participants must be within the first 5 days of coming down with symptoms, but within 1-2 days is better, said Dr. Lalezari.

11/20/09

Source
Conant Foundation and Project Inform. Surviving the Flu Epidemic. Community forum. November 10, 2009.