AIDS Trestment News
Flu Epidemic: Shots, New Treatments Availableby John S. James
It may not be 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 doctors 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 clinic(1) 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-approved drugs 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 TamifluTM," 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 that 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 the appearance 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 follow-up to make sure that the patient does not have complications, such as a bacterial infection (and also, we suspect, because it would be 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 that 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 PhysiciansOn January 12 the FDA published a public health advisory, "Safe and Appropriate Use of Influenza Drugs." Its three main points were:
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[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.]
Liver Toxicity, Ritonavir, and Hepatitis C: New Data Publishedby John S. James
The main purposes of this study were to determine how frequently liver toxicity occurs, particularly in patients who already had chronic hepatitis C or B. Data is needed because "the actual incidence of drug-induced hepatotoxicity and role of chronic viral hepatitis are poorly understood since anecdotal reports generally omit the number of exposed persons and may focus attention on exceptional cases or high-risk populations. Conversely, clinical trials are frequently restricted to persons at low risk for adverse events. Also, clinical trials underrepresent minority groups, women, and injection drug users, and may exclude those with chronic HCV or HBV infection."(1) (This study's population was almost 75% African-American, 24% white, and 2% other races, reflecting the population receiving HIV treatment at Johns Hopkins; no statistically significant racial differences in liver toxicity were found.) Severe liver toxicity was defined as grade 3 or 4 laboratory abnormalities of liver function tests (either AST or ALT), based on a definition used by the AIDS Clinical Trials Group (ACTG).
Results and ConclusionsThe major results of this study were:
No one knows why the risk of liver toxicity with ritonavir was much higher in this study than other studies.
Johns Hopkins Medical Institution summarized the results in a January 4 press release:
"Some doctors have been reluctant to use protease inhibitors, so they have prescribed other medications that are either harder to take or less effective, says Sulkowski [the lead author]. This study shows that liver toxicity is fairly high with these drugs and that ritonavir is more toxic than others. These drugs, however, can be used safely if liver enzyme levels are monitored closely.
"The study also shows that reluctance in prescribing protease inhibitors may do more harm than good. If you were to exclude every patient with hepatitis C from getting these medications, you would be denying treatment to many of those who would benefit from the drugs," said Sulkowski.
Abbott's ResponseAbbott Laboratories, the maker of ritonavir, issued a statement, which includes the following:
"Abbott has been monitoring and reporting results of abnormalities in liver function tests associated with Norvir use to regulatory authorities and to the medical community throughout the product's history. Our data of more than 900 patients in three controlled clinical studies demonstrated the overall incidence of severe hepatotoxicity with Norvir, using similar criteria as the JAMA article, is consistently in the range of 5-10 percent. In addition, we have observed in these studies that this incidence is increased in patients with underlying liver disease, such as HCV or HBV, and proactively notified the FDA in November 1996, which resulted in labeling reflecting these observations."
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Post-Exposure Prevention (PEP) for Sexual, Needle Exposure Opens in New York
San Francisco started a pioneering PEP program in 1998 (call 415-487-5538 24 hours a day if you may need this treatment in the San Francisco area). Data from the San Francisco program will be reported next week at the 7th Conference on Retroviruses and Opportunistic Infections (January 30 - February 2) in San Francisco.
In November 1999 Gabe Torres, M.D., a well-known AIDS physician in New York, started a PEP program for the New York area, through the Bently-Salick Medical Practice, PC. The drugs and counseling are free, thanks to contributions from industry, but laboratory tests and other medical expenses are the responsibility of the patient (or their health insurance). The treatment lasts either two or four weeks, with four office visits during this time and additional follow-up visits at three months and six months.
The New York PEP hotline can be reached 24 hours a day at 212-358-2400.
There are also PEP programs at the Fenway Community Health Center in Boston, and in a few other cities; we do not have a complete list. While any doctor can prescribe the medications, there are medical and practical difficulties to getting treatment started in time unless planning has been done in advance.
Dr. Torres has prepared a fact sheet on PEP and his program, which we reproduce in full below. For additional or more current information, see http://www.bentley-salick.com.
PEP Fact Sheet
What is HIV post-exposure prophylaxis (PEP)?HIV post-exposure prophylaxis or PEP is a potentially preventative treatment using antiretroviral (anti-HIV) drugs to treat individuals within 72 hours of a high-risk exposure to HIV.
Does PEP work?While there is no guarantee that PEP will work, one study of healthcare workers treated with AZT after a needlestick injury has shown that PEP may reduce the chances of HIV infection by over 80%. The Centers for Disease Control and Prevention (CDC) recommends PEP for healthcare workers who are exposed to HIV-infected bodily fluids through certain work-related accidents.
What is the PEP program at Bentley-Salick Medical Practice?Bentley-Salick Medical Practice, PC (BSMP) has developed the first New York area program to provide PEP treatment to individuals who report a recent (within 72 hours) high-risk exposure with a partner who is or is likely to be HIV infected. The pilot PEP program is open to 120 eligible patients at BSMP, a comprehensive outpatient diagnostic and treatment medical practice that provides internal medicine and infectious disease services, with expertise in delivering care to the HIV/AIDS population. The BSMP PEP program has received funding and medication to establish a 24-hour hotline and provide free drugs and counseling.* Any other medical care, lab tests, etc. are the responsibility of the patient. Most insurance plans are accepted as payment. The program provides PEP medication in conjunction with other prevention interventions, such as sexually transmitted disease (STD) screening and treatment, and a mental health program, including free behavioral counseling and adherence education. Information about patients is collected as part of a research study to evaluate the PEP program treatment and counseling and track trends in this high-risk population.
Who is eligible?The principal eligibility requirements for the BSMP PEP program are that an individual has had receptive or insertive anal or vaginal intercourse without a condom or with a condom that breaks or comes off with a partner who is or is likely to be HIV infected. PEP is also available for injection-drug-related exposures with a high-risk partner. The exposure must have occurred within the last 72 hours, preferably the drugs should be given within 36 hours of exposure.
What about PEP for sexual or needle-sharing exposures?There are no clinical trials or research that show PEP is effective in preventing HIV infection after sexual contact or sharing injection-drug needles. However, since PEP is recommended by the CDC for HIV-exposed healthcare workers because it reduces the chances of infection, many people believe that it should also be offered to those who are at risk from sexual or injection-drug-related exposures, especially since these are more common sources of HIV infection.
What is used for PEP treatment?The same drugs that are used to treat HIV infection are used for PEP. A combination of several antiviral drugs is tailored to the individual patient and prescribed for up to four weeks. These are powerful drugs that are very effective in fighting HIV, but they can have side effects and must be taken at specific times of the day on a regular schedule. In addition, there is only very limited knowledge about the use of anti-HIV drugs in HIV-negative people.
What are the advantages of PEP?PEP is intended to act as a prevention strategy that works on two levels: the first is to block the immediate HIV infection through the use of antiviral drugs, the second is to minimize the risk of future exposures by providing health care, STD treatment and risk-reduction counseling to those at high risk for HIV infection.
What are the disadvantages of PEP?One concern is that people will return to unsafe sexual and drug-using practices if they believe PEP will prevent them from becoming infected. There is no assurance and no study has established that PEP will prevent HIV/AIDS. PEP is not a replacement for avoiding exposure to HIV. The best way to prevent HIV infection is to avoid exposure in the first place through the consistent use of condoms and clean needles for injection-drug use. Through the counseling that accompanies BSMP PEP treatment, patients are engaged in programs aimed at more effective methods of HIV prevention.
How can the program be reached?The PEP hotline is accessible 24 hours a day at 212-358-2400. Intake counselors are available to evaluate eligibility and schedule in-person appointments. Individuals who are not eligible for the BSMP PEP program will be provided with information concerning other potential options for their care. General questions can be e-mailed to the program at email@example.com.
[*Funding and materials for the BSMP PEP program provided by Abbott, Agouron, APP Pharmacy, Bristol-Myers Squibb, Dupont Pharmaceuticals, Glaxo Wellcome, Gynetics, LifeStyles, Okamoto USA, Pharmacia and Upjohn, Roxanne and Virologic.]
Version 1.0, dated 10/14/99, IRB approval 10/14/99
African-Americans and AIDS Conference, February 24-25, Washington D.C.
The meeting is especially timely after a January 13 report by the U.S. Centers for Disease Control that among men who have sex with men, most of the newly diagnosed cases are among minorities. In 1998, the latest year for which statistics are available, whites made up 48% of these cases, minorities 52%. The rate of AIDS cases among African-American gay and bisexual men is now almost five times the rate among white gay and bisexual men.
From the brochure of the February conference:
"This course is designed for clinicians who care for African-American patients infected with HIV, as well as healthcare media, federal and state government agency representatives, federal and state legislators, AIDS service organization officers, social workers, pharmacists, nurses, peer counselors, church leadership and corrections healthcare personnel. The objectives are to familiarize participants with the epidemiology of HIV in the United States, current guidelines and cutting edge clinical modalities for the management of HIV, current research encompassing drug abuse and its connection to the HIV epidemic, social and psychiatric concerns of the HIV-infected patient, policy initiatives, trends and political issues which impact all HIV-infected patients."
The conference faculty has over 30 experts, including A. Cornelius Baker, John G. Bartlett, M.D., Anthony S. Fauci, M.D., Debra Fraser-Howze, Robert Fullilove, III, Ph.D., Robert C. Gallo, M.D., and Phill Wilson.
Abstracts (maximum two pages, for inclusion in the conference syllabus materials only) can be submitted until the deadline of February 1. They should be on one of five topics: Clinical management of HIV or complications from HIV; Case management; Outreach techniques; Testing and treatment counseling; or Substance abuse treatment. For more information, including the preliminary program and how to register, contact the Johns Hopkins Office of Continuing Medical Education, 410-955-2959, fax 410-955-0807, email firstname.lastname@example.org, or Web, http://www.med.jhu.edu/cme.
The Web site has online registration, or you can print a registration form that can be faxed or mailed to the office.
Retroviruses Conference, January 30 - February 2
The official conference Web site is http://www.retroconference.org; it will have searchable abstracts (hopefully before the conference begins), and some of the presentations. Usually the official site has the major background lectures, but not the slide sessions or late breakers where new data is presented. There will be other coverage on the Web, and we will have links to it on the AIDS Treatment News site, http://www.aidsnews.org.
Early news from the conference will also be reported in the press; most press reports will be on the AEGIS "AIDS" email list. Other news and commentary on the conference is likely to be on the treatment-oriented AIDS email lists, especially TREATMENT, PI-TREAT, LIPIDLIST, and others. All of these lists are free; for information on how to subscribe, see "Treatment and Related AIDS Email Lists," AIDS Treatment News #332; this article is available at: http://www.aids.org/immunet/atn.nsf/page/a-332-01.
The three activist meetings mentioned in our last issue (the January 29 meeting on long-term treatment effectiveness research, the daily one-hour meetings on what is happening at the conference, and the ACT UP meeting on intellectual property and treatment access in developing counties) have not yet announced exact times and locations. This information will probably be sent to the treatment lists mentioned above.
Reminder: Durban Conference Deadlines February 1
For more information, see the conference Web site, http://www.aids2000.com.
Copyright 2000 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.