Flu Epidemic: Shots, New Treatments Available
The U.S. and other countries have a major influenza epidemic this year--and the illness can be more dangerous to persons with HIV disease than to the general population. The number of people affected varies greatly by location, and no one can predict where the epidemic will spread, or when. Here are some things you should know:
It may not too late to get the flu shots; fortunately, this year's shots do protect against the flu strain causing the current epidemic. Persons with HIV should check with their doctor to make sure there is no reason they should not receive the vaccine. It may be difficult to get the shot at this time because of supply shortages.
(In San Francisco the flu shot is currently available at the San Francisco Health Department, 101 Grove Street 4th floor, room 405, Monday through Friday 9:00 a.m. to 1:00 p.m. and 2:00 p.m. to 4:30 p.m., no appointment necessary; the cost is $7, cash or credit/debit card only, no checks or insurance. You do not need to be a San Francisco resident. The clinic phone number is 415-554-2625.)
Earlier in the epidemic there was concern that in persons with HIV, the body's immune response to the vaccination could cause HIV viral load to increase temporarily. Today this seems to be much less of an issue, because HIV can usually be well suppressed by treatment, and the viral-load increase was temporary anyway. A recently published (September 1999) study in a military outpatient clinic1 found no change in viral load after influenza vaccination, but 100% effectiveness in preventing laboratory-confirmed influenza in this trial (10 of 47 placebo recipients were diagnosed with the illness, vs. none of the 55 who received the real vaccine).
It takes about two weeks for the vaccine to work and protect against influenza.
Your doctor can tell you where to get the shots. Often they are free at public clinics, or available for a small fee or for the cost of a doctor's-office visit.
If you are already sick, there are now four FDA-drugs approved for treating influenza. The main problem is distinguishing the flu from other illnesses, getting the prescription and the drug in time, and getting appropriate treatment for any complications, such as pneumonia or other bacterial infections.
The two new influenza drugs are expensive, and should be started within two days after symptoms began. (If you are at high risk for influenza--for example, not vaccinated and in an epidemic area--it might be a good idea to check with your doctor's office in advance, as to what to do if you develop influenza symptoms.)
Doctors have rapid (half an hour or less) laboratory tests to tell if a person really has influenza. When there is a major epidemic in the area, most persons who have the symptoms will have the illness--and since the test requires an office visit with associated delays, and exposes other persons to the virus, in some cases it might be better to treat immediately. But the test could be important if the person does not have influenza and needs further diagnosis to determine if there is a bacterial infection which may require antibiotics.
Symptoms of the flu are different from those of a cold and are more severe, and are likely to start very suddenly. "Typical symptoms of flu include sudden onset of fever, cough, headache, fatigue, muscular weakness, and sore throat" (quoted from "Patient Information about Tamiflu™," published by Roche Laboratories Inc., with approval of the FDA). People report feeling like they were "hit by a truck," often just a few hours after they were feeling well.
Of the four approved drugs for treating influenza, most of the interest is in the two recent ones, approved within the last year: Tamiflu (oseltamivir), developed by Gilead and marketed by Roche, and Relenza (zanamivir), by Glaxo Wellcome. Both of these have the same mechanism of action; the main difference is that Tamiflu can be taken orally, while Relenza must be inhaled (through an inhaler which comes with the medication--the patient should be shown how to use the inhaler at the pharmacy). Both drugs are taken twice a day for five days. Neither has been approved for prevention, but published studies have found that these drugs are probably more than 80% effective in preventing influenza in persons exposed to it.2,3
A practical problem is that both drugs should be started within two days of symptoms, so it may be hard to get a prescription in time, depending on how one's physician operates; an appointment next week would be too late. We have also heard of problems getting "urgent care" facilities to prescribe the drug, since they are not set up to do followup to make sure that the patient does not have complications, such as a bacterial infection--(and also, we suspect, because it would hard to bill much for a transaction that might be only a phone conversation with the patient and then a prescription called into a pharmacy). Similar problems can occur when going to a physician who is not one's regular doctor.
TAMIFLU "is indicated for the treatment of uncomplicated acute illness due to influenza infection in adults who have been symptomatic for no more than 2 days" (from the official labeling of the drug). No one knows that it would not work after two days from the beginning of symptoms; no trial has been done in this population so there is no proof either way. [We have heard one anecdotal report of someone who took it after five days and believed that it worked well; however, there is no way to know whether this person would have done equally well without the drug.]
TAMIFLU can be taken with or without food. It has almost no known interactions with other drugs--but it has not been tested to see if it interacts with the antiretrovirals used in HIV treatment. It does not seem to interact with the p450 enzyme system, the source of most of the drug-interaction problems with ritonavir (Norvir®) and some other HIV drugs. The main side effects were nausea and vomiting (but this drug has not been studied in persons with HIV, and the side effect profile might be different).
The other new influenza drug, Relenza® (zanamivir), was available before TAMIFLU, and is now approved in 30 countries. The two are similar, except that Relenza must be inhaled.
Both of these drugs appear to be effective against all known strains of influenza (although resistant virus can be created in the laboratory), strongly suggesting that they will also work against new strains which will emerge in the future. Vaccines are not always effective against new strains, because it takes six months to prepare the vaccine, and when the vaccine decisions are made, no one knows what virus, if any, will cause the next winter's epidemic. This year we are lucky that scientists guessed right, and the vaccine is effective; in future years it may not be, and then the drugs will be especially important.
The two older medications are amantadine (brand names Symmetrel and others), and rimantadine (Flumadine). These drugs, which are chemically similar to each other, have been approved for years in the U.S. for treatment and for prevention of influenza A (which causes the large epidemics, including the current one), but not influenza B. The mechanism of action is completely different from that of the new drugs. And there are more problems with side effects than with the new generation of influenza treatments.
FDA Advice to Physicians
On January 12 the FDA published a public health advisory, "Safe and Appropriate Use of Influenza Drugs." It's three main points were:
1. "Vaccination remains the primary method of preventing and controlling influenza."
2. "Always consider the possibility of primary or concomitant bacterial infection when making treatment decisions for patients with suspected influenza." and
3. "Use special caution if prescribing Relenza to patients with underlying asthma or chronic obstructive pulmonary disease (COPD)." [This warning applies only to Relenza, which is taken by inhalation.]
For More Information
The full text of the FDA advisory to health professionals is at http://www.fda.gov/cder/drug/advisory/influenza.htm
For recent information on influenza in your area (in the U.S.), see http://www.fluwatch.com/index2.html, a site maintained by industry. A map of the U.S. shows in red the states where the epidemic is worst (as of January 18, these are Arkansas, Alabama, Connecticut, Florida, Georgia, Iowa, Illinois, New York, Oklahoma, Tennessee, Texas, West Virginia, and Wisconsin); you can select your state or enter your ZIP code to get information for your area. In California, there is an epidemic now in much of the state, including Los Angeles and San Diego, but it is less severe in the San Francisco area, although there are cases here.
More information about each of the new drugs can be found on Web sites maintained by their manufacturers: http://www.tamiflu.com and http://www.gsk.com/index.htm
On December 17 the U.S. Centers for Disease Control published a report on the two new drugs, "Neuraminidase Inhibitors for Treatment of Influenza A and B Infections," in the MMWR (Morbidity and Mortality Weekly Report). It is more readable than the official "labeling" which is found on the manufacturers' Web sites. It is available at http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/rr4814a1.htm
An excellent background article on influenza, published in Scientific American, January 1999, is "Disarming Flu Viruses," WG Laver, N Bischofberger, and RG Webster; it is available in public libraries, or at http://www.sciam.com/article.cfm?colID=1&articleID=00023064-8039-1CD6-B4A8809EC588EEDF
[The authors note that much more deadly influenza strains can develop, like the one that killed 20,000,000 people in 1918--and that in a worst case, a new influenza epidemic might kill 30% of the world's population before a vaccine against it could be created. There may have been a near miss in 1997, when a fatal strain from poultry infected people in Hong Kong; this epidemic was stopped before it could evolve the ability to spread from person to person, by slaughter of all the poultry in Hong Kong. The two new drugs are likely to be effective for treating or preventing any influenza strain (and the two older drugs might be effective as well); hopefully someone is paying attention to whether the supplies, manufacturing, and distribution capacity would be available to respond to a worldwide emergency.]
References
1. Tasker SA; Treanor JJ; Paxton WB; and Wallace MR. Efficacy of influenza vaccination in HIV-infected persons. A randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine. September 21, 1999; volume 131, number 6, pages 430-433.
2. Monto AS, Robinson DP, Herlocher ML, Hinson JM, Elliott MJ, and Crisp A. Zanamivir in the prevention of influenza among healthy adults: a randomized controlled trial. JAMA. 1999; 282, pages 31-35.
3. Hayden FG, Atmar RL, Schilling M, and others. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. New England Journal of Medicine. 1999; 341, pages 1336-1343.
