AIDS Trestment News
February 18, 1999

Kaposi's Sarcoma: New Topical Treatment Approved

On February 3 Ligand Pharmaceuticals announced that the FDA had approved Panretin® Gel (alitretinoin) for topical treatment of Kaposi's sarcoma; an advisory committee had recommended approval by an 8-1 vote last November. The company has filed for approval in Canada and Europe.

Patients apply the gel twice a day. According to Ligand, the cost of a four to six month course of therapy is between $3,900 and $5,800. The main side effect is skin irritation where the drug is applied; in seven percent of the patients, skin toxicity was severe enough to cause them to withdraw from the trials.

Panretin capsules (for oral use) have been tested in phase II clinical trials for Kaposi's sarcoma, and tested for several cancers.

The active ingredient, alitretinoin (also known as 9-cis retinoic acid), is a derivative of vitamin A, and also a hormone naturally present in the body.

Results of two trials involving 402 patients were presented at the recent Retroviruses conference.¹

References

Retroviruses Conference: Finding Information on the Web

by John S. James and Tadd Tobias

Where to look on the Web for information about the 6th Conference on Retroviruses and Opportunistic Infections (Chicago, Jan. 31 - Feb 4) depends on what you want.

Non-Technical Overview for Patients (and Medical Professionals)

Strategy Trials: The Answer?

During the 6th Conference on Retroviruses and Opportunistic Infections (Chicago, January 31 - February 4, 1999), we received much promotional material on drugs now being marketed or about to be approved soon. We do plan to outline some of the major drug-specific news, as there is information worth knowing.

But there was also widespread disappointment at the paucity of practical treatment information -- despite the promising advances in research, especially immunology. Somehow the piles of faxes, press releases, and other promotional materials -- the 12-week, 24-week, or 48-week data, seldom comparable between trials and usually highlighted to promote one drug, or one company's drugs -- do not add up to an intelligent approach to treating patients.

Doctors and patients have many treatment options today, but little help with the questions of which treatment strategies are best -- which choices now will prove to have been the most beneficial, not only in 12 weeks or 48 weeks, but years later, even after the initial treatment choice may have failed or otherwise been replaced with different treatments.

For several years there has been a growing call for "strategy trials" to answer just these questions -- but in practice, few of them are happening. Much of the fault is with the pharmaceutical companies, which are mainly interested in trials likely to promote their products. Government-funded trials help to fill the gap, but often there is difficulty getting assistance from the companies. And public funding can go only so far in doing the drug development which is supposed to be the responsibility of private companies.

Another important difficulty with strategy trials is more inherent, harder to solve with any amount of altruism. Typically these trials will randomly assign patients to a certain starting drug regimen; and later, if and when that regimen fails, will assign them in some protocol-defined way to a second regimen. The goal is to learn which of two or more treatment strategies is best -- considering not only the initial drug combination, but also what happens if that combination later needs to be replaced.

Unfortunately it is likely to take much longer to get useful information from such a strategy trial, than from one which tests only a starting regimen, because volunteers must fail one treatment and then have enough experience with the second to test how well it is working for them. Unless there are enough volunteers with substantial experience with the second regimen to allow statistically reliable conclusions about it, the whole scientific point of including it would be lost. And researchers are usually reluctant to release much preliminary information while a trial is ongoing, lest the final results be affected in unpredictable ways. Including all the other delays, such as approvals and recruiting, years are likely to elapse between a strategy trial's design and its results; and with the speed of AIDS treatment development today, the whole picture is likely to have changed greatly by that time, which can easily make the trial results largely irrelevant to the most important issues which doctors and patients will need to address. This has already happened again and again with trials designed years before their results were released; strategy trials are even more vulnerable, both because they usually take longer, and because their protocols are more complex and therefore more vulnerable to a changing medical environment.

One way to approach these problems is to step back from the ideology that medicine should be guided only by scientific trials, and acknowledge that clinical experience and judgment is still as important as clinical trials in making practical treatment decisions, and will probably remain so for the foreseeable future. Then we can more systematically address the issues of how to improve data collection to better support clinical experience. Steps in the right direction include better followup of trials, and also large databases to more systematically collect outcome information from non-randomized medical care (such as the CHORUS project of Glaxo Wellcome, or the community-initiated HIV Treatment Data Project).

A better understanding of clinical trials -- including their limitations, and their real-world role in medical decision making -- could lead to better trials, and also to more attention on improving the collection and use of non-randomized data to support clinical practice.

San Francisco: New HMO Problems Threaten Access to Care

About 2,000 patients in the San Francisco area may have to change doctors or health plans, because of a dispute between managed-care organizations. For persons with HIV, the problem may be especially severe for those seeing doctors at the Davies medical center.

This situation occurred because two HMOs, HealthNet and Blue Shield, will not renew their contract with BayCare, a relatively small IPA (independent practice association) in San Francisco. The patients affected are those with HealthNet or Blue Shield coverage, who are seeing physicians who are dependent on BayCare and cannot move their patients to another IPA. (At this time physicians cannot join the dominant IPA, Brown & Toland Medical Group, because of action against Brown & Toland by the U.S. Federal Trade Commission.)

William Owen, M.D., told AIDS Treatment News, "My office has been inundated by calls from patients who were alarmed when they received the rather curt letter from Blue Shield HMO informing them that, because BayCare was dropped as an independent practice association (IPA) by Blue Shield HMO, and because their physician (Dr. Owen) is not a member of another IPA that has a Blue Shield HMO contract, the patient would be required to select a new M.D. by February 26. This letter, unfortunately, strikes at the heart of many provider-patient relationships that have been nurtured over many years...

"I have requested that Blue Shield HMO patients file protests with the HMO, and send copies of their letters to the Department of Corporations (which regulates HMOs in the State of California), Assemblywoman Carole Migden (who has had a long-standing interest in lesbian and gay health issues, including treatment of patients with HIV/AIDS, and has dealt with earlier problems with access by patients to their long-term providers through BayCare Medical Group), to President of the San Francisco Board of Supervisors Tom Ammiano, and to the Federal Trade Commission (FTC), which is needlessly preventing a dozen or so former Davies Medical Center physicians from joining Brown & Toland Medical Group (an organization that consists of over 1,000 physicians) on the grounds that this addition of a minuscule number of providers would somehow constitute a 'restraint of trade'."

Dr. Owen noted that the other HMO, HealthNet, has worked out a temporary arrangement until it negotiates a contract with another IPA with which the physicians are affiliated.

For more information, see "Feud Erupts Between HMOs, Doctors' Group," San Francisco Chronicle February 11, 1999; also see "New Healthcare Economics Threaten HIV Specialization, Patient Choice, & Quality Care," AIDS Treatment News #311, January 22, 1999.

Tuberculosis Control: Many Cases Found Transmitted Despite Negative Result on Standard Test

The standard test for infectious tuberculosis, the acid-fast bacilli (or AFB) smear, fails to detect many people who are in fact infectious, new research has shown.¹ At least one sixth of TB patients diagnosed in San Francisco since 1991 acquired the infection from persons who were not detected as infectious by the standard test. This was determined by analysis of a database of "DNA fingerprinting" of the TB bacteria from over 1,300 patients. The research was supported by the U.S. National Institutes of Health, and the McLaughlin Foundation of Canada.

The findings "suggest that while the use of the sputum smear does identify the most infectious patients, those with negative smears should not be considered non-infectious, particularly to highly susceptible people such as those infected with HIV," said Peter M. Small, M.D., one of the researchers, who is Assistant Professor of Medicine at Stanford Medical Center.

The AFB smear is still useful because it detects those who are most infectious.

This new information could improve tuberculosis control around the world, if it is applied. A major problem is that more sensitive tests, such as sputum cultures, are usually too expensive for use in developing countries. The researchers said that it is imperative that a more sensitive but affordable test be developed quickly. "It is a travesty that in most parts of the world, a disease which kills three million people a year is still diagnosed with a 100-year-old test," said Dr. Small.

References

Keep Your Medicare In Force As You Go Back to Work

(What To Do And When To Do It)

by Thomas P. McCormack

[We reprinted this article from The Voice of T-II CANN (the newsletter of the Title II Community AIDS National Network); the author gave us updates to reflect the regulations as of February 16, 1999. Note that this information is for persons on Medicare (not Medicaid) as a result of long-term disability, who are returning to work. JSJ]

The following are suggestions to keep your Medicare, as you transition to the workplace.

1. You get twelve months (a nine month Trial Work Period, followed by a three month Grace Period) of Social Security Disability Insurance (SSDI) checks when your adjusted gross earnings total over $200 monthly. Medicare Part A is "free" and Medicare Part B's premium of $45.50 gets deducted out of your SSDI check.

2. Once the twelve months have passed, visit the Social Security office -- or write them by certified mail -- to inform the agency that the SSDI checks should be stopped, but that you want the Medicare to continue! If you don't, the checks will continue and you may be tempted to spend them. However, spending them is fraud under the Social Security statute. Ask for a written confirmation that they've continued your Medicare.

3. Whether or not SSA responds to your request for continued Medicare, you must now pay your Part B premium of $45.50 monthly (remember, the SSDI check from which it was deducted has now stopped -- or if the checks haven't yet stopped, you're returning them, via certified mail). If you can afford to pay your premium, send a check for $45.50 payable to the U.S. Treasurer, with your Medicare card number, and an explanation that your SSDI has ended, to: Medicare Premium Collection Center, P.O. Box 371384M, Pittsburgh, PA 15250.

4. If you can't afford to pay the Medicare Part B premium, apply at the Welfare office (not SSA) for the QMB, SLIMB, and/or QI(I) programs. [Note: QMB means Qualified Medicare Beneficiary; SLIMB means Specified Low-Income Medicare Beneficiary; and QI(I) means Qualified Individual (I), where the 'I' is Roman numeral one.] If your gross monthly earnings are under $1,896 (or even higher, if you're paying out-of-pocket cash medical costs) welfare will pay the Part B premium for you; be aware that some welfare offices have not been properly trained in the eligibility rules for these programs. If you encounter difficulty applying to these programs, ask a supervisor to contact the state's head Medicaid eligibility policy staff in the state capital for guidance.

5. After 45 months back at work, "free" Part A Medicare coverage ends -- but you can still keep it if you want. Don't rely on Social Security to tell you this. Visit or send a certified letter to the SSA office stating that you want to stay enrolled in Medicare Part A, even though you've been back at work for 45 months. Ask for a written confirmation that they've continued your enrollment. Whether you hear from them or not, start sending your Medicare Part A premium to the Medicare Premium Collection Center, P.O. Box 371384M, Pittsburgh, PA 15251, giving your Medicare number and informing them that you've used your "free" forty-five months-back-at-work Part A coverage and are paying it yourself now. Make the check payable to the U.S. Treasurer.

6. Medicare Part A premiums are either $170 monthly, if you worked with FICA deductions taken from your paycheck for over 7.5 years during your working life; or $309, if you worked with FICA deductions taken from your paycheck for less than 7.5 years. You'll have to calculate how many quarters you worked to find out which of the two Part A premium rates apply to you. (You can try calling 800-772-1213 for assistance, but this question is probably too complex for a quick and easy answer over the telephone.)

7. If you can't afford to pay the Medicare Part A premium of either $170 or $309, apply for the Qualified Disabled Working Individual (QDWI) program at the welfare office (again, not SSA). If your monthly earnings are under $2768 (or even somewhat higher if you're paying out-of-pocket medical costs yourself) the state will pay the Part A premium for you. Again, most welfare staff know little about this program -- so you may need to ask a supervisor to contact the state Medicaid eligibility policy staff to properly process your case!

8. Medicare Part A and Part B premium amounts change each January 1. After about November 15 of each year, the staff at 800-772-1213 can tell you what the new premium amounts will be for the coming year.

9. The income levels for QMB, SLIMB, QI(I), and QDWI go up each year about April 1. Ask your local welfare office what the new income levels will be, or consult with a benefits advisor at the agency you rely on for casework help.

10. Keep your Medicare even if you're offered good health insurance in a new job! This is important because:

• If you lose your job, you'll still have the Medicare.

• Having both Medicare and the job insurance will reduce your deductibles and copayments. (Remember, you're still going to have high medical and drug bills.)

• Medicare covers many services not adequately covered by private insurance, such as: unlimited home health and mental health therapy visits; hospice care; hospital care for mental health, alcoholism, or drug problems; and medical equipment/supplies purchases and rentals.

Medical Marijuana: Major AIDS Organizations Seek Legal Access

Major AIDS organizations -- including the AIDS Action Council, San Francisco AIDS Foundation, AIDS Project Los Angeles, Northwest AIDS Foundation, Latino Commission on AIDS, AIDS National Interfaith Network, Mothers' Voices to End AIDS, and Whitman-Walker Clinic -- have asked General Barry McCaffrey, director of the Office for National Drug Control Policy, to help change Federal policy to allow patients to legally use marijuana when recommended by their physician. Here is the text of the February 17 letter, which is an excellent statement on this issue. [JSJ]

Dear General McCaffrey:

As advocates and care givers for people living with HIV disease and AIDS, we are writing to urge you to help break the bureaucratic logjam that is keeping a potentially life-saving medicine virtually inaccessible to thousands of people living with AIDS and other debilitating illnesses.

That medicine is marijuana. Marijuana's therapeutic uses are well documented in scientific literature. Recent scientific studies have confirmed what has been reported to us by hundreds of people living with HIV -- that marijuana can be safely used to reduce nausea and vomiting, stimulate appetite, and promote weight gain. Marijuana is widely recognized by physicians specializing in AIDS care as an important component of treatment for some patients who suffer from symptoms of advanced-stage HIV disease and the multiple-drug therapies used to manage HIV.

Today, thanks to one federally approved clinical study of marijuana for people living with AIDS, sixty-four patients receive marijuana legally from supplies grown by the federal government. However, thousands of Americans, many of them people living with HIV, use marijuana as a medicine illegally, putting themselves at risk of arrest and prosecution. Because the practice is illegal, most patients use marijuana without medical supervision. Marijuana's illegality means that patients cannot be sure of obtaining standardized products that are free of contaminants. People should not have to risk their health or jail to receive needed medical care.

For this reason, thirty-five state legislatures have passed laws supporting the use of marijuana as a medicine. In addition, voters in six states (Alaska, Arizona, California, Nevada, Oregon, and Washington) and the District of Columbia have recently approved ballot measures legalizing the medical use of marijuana within their borders -- nearly one in five Americans lives in a state whose voters have approved medical marijuana. Now, the nation is looking to the federal government to begin to show compassion and flexibility on this issue.

You may be aware that the standard Food and Drug Administration approval process has been streamlined for several medications important to people living with HIV disease and AIDS. Drugs shown to fall within an acceptable standard of safety have been made available to patients before completion of all scientific trials proving effectiveness. This special procedure has helped thousands of patients to obtain life-extending benefits from new medications, and has contributed directly to building the science base for such new drugs.

Our request is simple. Just as other promising AIDS medications have been made available prior to final FDA approval, so too should marijuana, when recommended by a physician, be made available to patients who choose to use it.

There is not much question about the relative safety of marijuana -- it has been heavily studied around the world. These studies have revealed an important fact: there is no lethal dose of marijuana. Besides this finding, occasional marijuana smoking under controlled circumstances has not been proved to be dangerous. In sum, the known risks of marijuana are clearly within a range of acceptability sufficient to allow individual physicians and patients to monitor its use, and its results. Under these circumstances, making marijuana immediately available on a quasi-experimental basis to people living with AIDS, when their physicians request it, is a moderate step that can add to the federal government's responsiveness to the epidemic.

We appeal to you, General McCaffrey, because you are in a unique position to provide leadership on this issue. Science and compassion should dictate our nation's policy regarding medical treatment. However, politics has stood in the way of the approval of marijuana as a legal medication, and the full development of a science base leading to FDA approval could still be years away. We call upon you to be a part of the political solution. We ask that you publicly encourage your colleagues in the administration to respond positively to the scientific and public support for making marijuana medically available.

Washington D.C.: Retroviruses Conference Update

February 25

A review of treatment information from the 6th Conference on Retroviruses and Opportunistic Infections (Chicago, February 1999) will be presented at the Hyatt Regency on Capitol Hill (400 New Jersey Avenue, NW, near Union Station or Judiciary Square), Thursday February 25, 6:30 p.m. - 9:30 p.m.; refreshments will be served. There is no charge for this program.

Speakers are:

• Joseph Timpone, M.D., Associate Professor of Medicine, Division of Infectious Diseases, Georgetown University, on "Expanded Treatment Options."

• Richard Elion, M.D., in private practice, on "Implications of Immune Reconstitution."

• Lark Lands, Ph.D., on "Treatment Advocates' Perspective" (an overview of information of interest from the daily treatment activist meeting during the Retroviruses conference).

The moderator will be Ron Mealy of the Carl Vogel Center. For more information, call the Carl Vogel Center at 202-638-0750.

This program is sponsored by the Carl Vogel Center, with educational grants from Agouron Pharmaceuticals, Glaxo Wellcome, and Bristol-Myers Squibb.

11th National HIV/AIDS Update Conference

San Francisco, March 23-26

This annual conference -- organized this year by the American Foundation for AIDS Research, and chaired by Mervyn Silverman, M.D., M.P.H. -- is intended for "health care providers, physicians, pharmacists, nurses, community-based and HIV/AIDS service organizations, social service providers, mental health professionals, members of local public health agencies, hospital planning and service providers, elected and nonelected community leaders, state and local government representatives, and volunteers and individuals living with HIV and AIDS." Its five tracks are: affected communities; mental health; prevention; public policy; and research and clinical management. Continuing medical education credit is available.

For more information, contact KREBS Convention Management Services, 415-920-7000, fax 415-920-7001; or visit www.nauc.org.

ISSN # 1052-4207

Copyright 1998 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.