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AIDS Trestment News
August 7, 1998

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T-20: New Trial Enrolling, 9 U.S. Cities

by John S. James

On July 30 Trimeris, Inc. announced a trial of T-20, an experimental drug based on an important new approach to antiretroviral treatment. This study, called TRI-003, will enroll up to 78 volunteers at 11 sites in 9 U.S. cities. It will be relatively easy to qualify for entry, since volunteers can be on any stable antiretroviral regimen (or on none at all) -- and there are no exclusions for previous use of any antiretrovirals. A viral load of at least 5,000 is required (so that antiretroviral activity of the drug can be measured), and there are some other entry criteria.

T-20 is a synthetic 36-amino-acid peptide which is identical to part of the HIV virion itself; it remains outside human cells and blocks a specific step in the process by which HIV enters new cells (see AIDS Treatment News issue #293, April 17, 1998; also #279, September 19, 1997). In a previous human trial T-20 caused a very rapid drop in viral load, with no known adverse effects from the drug. But that early test was limited, because the largest and most effective dose was tested in only four patients; also, T-20 was injected twice a day, an inefficient means of delivery. The new trial will test continuous administration of T-20 by subcutaneous infusion, using a small, pager-size pump, developed by MiniMed Inc., which is currently in widespread use for delivering insulin to diabetics.

The new trial will run for 28 days; its purpose is to learn more about the antiretroviral activity, safety, and plasma pharmacokinetics of T-20. Longer tests will begin after more has been learned about dosage, and after long-term animal safety data has been obtained from ongoing tests. According to Trimeris, volunteers who achieve sustained HIV suppression on TRI-003 will be eligible for another T-20 study which will explore long-term use.

TRI-003 replaces TRI-002, a smaller trial announced June 25. TRI-002 would have required indinavir failure as an entry condition, and also required three particular antiretrovirals to be used in combination with T-20.


Comment

Trimeris changed its study plans after discussions with the trial investigators, community advocates including this writer, and the FDA. We believe that the specific drug requirements of earlier designs would have created serious recruiting, adherence, and other problems, for no purpose. Since T-20 has a completely different mechanism of action than any other antiretroviral in human use, all exclusions for prior or concurrent treatments are unnecessary; what the trial does need is treatment stability, so that the effects of T-20 on viral load can be determined. The TRI-003 design got it right.

One theoretical concern about volunteering for this study is that since so little is now known about how to use T-20, it is possible that doses tested will be too low to fully suppress HIV, which could lead to the development of viral resistance and prevent volunteers from benefiting from T-20 later. Although this risk appears to be small, resistant virus has been created in laboratory cultures. Volunteers and their physicians will have access to viral load results during TRI-003.

Also, the earlier trial found a very rapid drop of viral load with an adequate T-20 dose -- perhaps even faster with T-20 alone than with the combination antiretrovirals currently in use. This rapid decline of virus, plus the avoidance of most of the adherence and absorption variability of oral drugs, may reduce the risk of viral resistance. And even if T-20 resistance did occur, there would almost certainly be no cross resistance with any other antiretroviral in human use.


For More Information

For information about volunteering for this trial, call the study coordinator at a site near you (the "contact" listed below). The trial locations are listed alphabetically by city (New York and San Francisco each have two sites). Note that each site cannot begin the trial until it has been approved by the local IRB (institutional review board). But volunteers can call now for more information, and to begin the process or at least get on a waiting list.

Birmingham: University of Alabama. Principal investigator: Michael Kilby, M.D. Contact: Leslie Alldredge, 205-975-9128.

Boston: Community Research Initiative of New England. Principal investigator: Cal Cohen, M.D. Contact: Ruth Cooper, 617-566-4004 ext. 49.

Chapel Hill: University of North Carolina. Principal investigator: Joseph J. Eron, M.D. Contact: Limh Ngo, 919- 966-6712.

Chicago: Northwestern University. Principal investigator: Robert Murphy, M.D. Contact: Joyce Drury, R.N., 312-908-7873.

Houston: University of Texas. Principal investigator: Roberto Arduino, M.D. Contact: Hilda Cuervo, 713-500-6751.

Los Angeles: UCLA. Principal investigator: Margrit Carlson, M.D. Contact: Christine MacNaughton, 310-206-6414.

Maitland, Florida: Central Florida Research Initiative. Principal investigator: C. Jeffrey Goodgame, M.D. Contact: Bill Emery, R.N. C.C.R.C., 407-647-3960.

New York City: Bentley-Salick Medical Practice. Principal investigator: Ramon Torres, M.D. Contact: Mary Catherine George, 212-414-4624.

New York City: NYU Medical Center. Principal investigator: Fred Valentine, M.D. Contact: Karen Cavanaugh, 212-263-8707.

San Francisco: Quest Clinical Research. Principal investigator: Jacob Lalezari, M.D. Contact: Dr. Lalezari, 415-353-0800.

San Francisco: San Francisco General Hospital. Principal investigator: Paul Volberding, M.D. Contact: Doug Raggett, 415-476-9296 ext. 312.



New Vaccine+HAART Treatment Trial Enrolling at NIH

by John S. James

A small trial at the U.S. National Institutes of Health (NIH) will test a new kind of HIV vaccine, plus standard antiretroviral therapy, to try to bring back HIV-specific immune responses in volunteers with relatively early HIV disease.

This trial is open to persons who currently have a CD4 count of over 500, and who either are on antiretroviral treatment already, or are willing to begin treatment. All study medications will be paid for while the patient is in the trial, which will last up to 18 months. In addition to the antiretroviral treatment, there will be six injections of the vaccine during a period of one year. NIH will pay for transportation (except for the first trip), so volunteers do not need to live in the Washington D.C. area.

Volunteers must never have had a CD4 count under 300, unless the low count occurred during acute HIV infection.

The vaccine being tested consists of two HIV peptides of the viral envelope, including the V3 loop. This is the first trial in which these peptides together will be given to humans. Each has been tested separately in a few people, however (without the antiretroviral therapy), and no adverse effects have been seen.

Intensive immunologic studies will be performed to see whether HIV-specific responses -- especially T-helper, cytotoxic T lymphocyte (CTL), and neutralizing antibody responses -- can be restored by this vaccination while the virus is being suppressed by the drugs. Such effects on HIV-specific immunity have already been found in animal tests, and some have been seen in the early human tests with the peptides, even without the antiretroviral treatment.


Comment

Interest is growing rapidly in finding ways to restore HIV-specific immune responses, which are usually lost very early in the infection. A similar study, but using a different vaccine, reported strikingly successful results at the recent 12th World AIDS Conference in Geneva (abstract #31227, late breaker session #LB 9; see report in AIDS Treatment News #298, July 10, 1998).

These HIV-specific responses are maintained naturally by long-term nonprogressors, but are lost by the great majority of patients, who do progress to HIV disease. There is no data yet on whether restoring these responses by treatment is clinically beneficial.


For More Information

For more information about volunteering for this study, contact either Tino Merced-Galindez, R.N. (800-772-5464 ext. 562, or 301-496-8959, or merced@box-m.nih.gov), or Richard Little, M.D. (800-772-5464 ext. 657, or rlittle@helix.nih.gov), at the HIV and AIDS Malignancy Branch, National Cancer Institute.



Ritonavir Capsule Manufacturing Problems Will Require Switch to Liquid Formulation

by John S. James

On June 27 Abbott held a conference call to inform the AIDS community that a manufacturing problem has halted production of ritonavir (Norvir™) capsules. The supply on hand will start to run out in August (some pharmacies may still have capsules later), and then patients will need to switch to the liquid formulation of ritonavir, which remains available (or switch to a different treatment regimen). No one knows when the manufacturing of the capsules can be resumed.

The problem is that the ritonavir in the capsules started to crystallize. While the crystal is still the same chemical, it does not dissolve as fast, and therefore would be absorbed differently. Abbott discovered the problem during routine quality-assurance tests.

According to Abbott, all the capsules which have been shipped to pharmacies and distributors are OK.


Switching to Ritonavir (Norvir) Liquid

The liquid formulation (sometimes called "Norvir oral solution") provides the same drug as the capsules. Therefore the switch should not require a doctor's visit, although the pharmacist may have to call the doctor to get permission to substitute the different formulation when the prescription for the capsules needs to be refilled and the pharmacy has no more capsules in stock. It is likely that most people will change to the liquid formulation, since switching to a different protease inhibitor, or other HIV treatment, involves more difficult medical decisions.

The price of the drug should be about the same for either formulation.

The main disadvantage of the liquid is its very bad taste. The package insert suggests, "Patients may improve the taste of Norvir oral solution by mixing with chocolate milk, Ensure®, or Advera® within one hour of dosing."

Until now the oral solution has been used mostly for children, so that they could be given the correct dose for their body size. Since the bad taste is a serious obstacle in getting children to take the drug, pediatricians have had the most experience in masking the taste. One suggestion is to take a spoonful of chocolate syrup before the dose, and then again after the dose. A popsicle may help reduce the bad taste by chilling the taste buds. Another suggestion is to use a straw to deliver the drug to the back of the throat. (We thank Search for a Cure for this information, which it learned from pediatricians who use the liquid formulation.)

Note that the oral solution (unlike the capsules) should not be refrigerated by the patient. According to the package insert:

"Recommended storage: Store Norvir oral solution at room temperature 68 degrees F to 77 degrees F (20 degrees C to 25 degrees C). Do not refrigerate. Shake well before each use. Use within 30 days from dispensing.

"Product should be stored and dispensed in the original container. Avoid exposure to excessive heat. Keep cap tightly closed."

What if the temperature in one's home goes above 77 degrees? A preliminary recommendation (which Search for a Cure heard from Abbott) is that if the temperature gets hotter than 86 degrees, put the drug in the refrigerator. But if any official recommendation is issued in the future, it is the one that should be followed.

The Norvir Web site (http://www.norvir.com) has measuring instructions:

"Each Norvir capsule contains 100 mg of active drug, and each mL of Norvir liquid contains 80 mg of active drug. For your convenience, Norvir liquid comes with a dosing cup that provides markings indicating the amount of liquid to be taken for the two most common doses. It is important to measure the correct dose of Norvir; therefore, the dosing cup has been specially designed to provide the right dose of Norvir liquid. This cup should be used to measure a dose. Please be advised that when measuring a dose, the cup should be placed on a flat surface at eye level, and the cup filled with Norvir liquid to the line showing the appropriate dose. You should wash the dosing cup with soap and warm water as soon as possible. The dosing cup is not dishwasher safe.

"The following conversion equation may be helpful:

"6 Norvir capsules (100 mg each) = 7.5 mL of Norvir liquid (1 1/2 teaspoons)

"4 Norvir capsules (100 mg each) = 5 mL of Norvir liquid (1 teaspoon)."


For More Information

For more information about the ritonavir capsule shortage and the oral solution, call your physician. Or check Abbott's Web site at http://www.norvir.com, or call the Norvir information hotline, 800-637-2400, 7:00 a.m. to 7:00 p.m. Central time.



Geneva Medical Report Now on Web

by John S. James

An excellent two-hour summary of major practical themes from the 12th World AIDS Conference, intended primarily for HIV care providers, is now available in both text and audio on the Web. This program, two panel discussions sponsored by the Johns Hopkins University AIDS Service, the University of California San Francisco AIDS Program at San Francisco General Hospital, and the U.S. Health Resources and Services Administration (HRSA), had a projected audience of 100,000 through an interactive satellite broadcast, a simultaneous interactive netcast, and the transcript and audio which is the subject of this announcement. Unlike most medical programs today, it was not financed by pharmaceutical companies.

The discussions were led by John G. Bartlett, M.D., from Johns Hopkins, and Paul Volberding, M.D., from San Francisco General Hospital. Since this conversation occurred a month after the conference, the eight panelists, all physicians, had had time to reflect on which information was most important for medical care today and in the near future. While intended mainly for medical professionals, this material will be useful for patients as well.

A disadvantage of the archived program is that the transcript was made quickly, without time for the presenters to correct it; as of this writing there were minor ambiguities or possibilities for misinterpretation in the written version. The audio feed, which is good quality, avoids most of these problems, but requires fairly modern computer equipment and software. Individuals or organizations might want to tape the audio to make it available to persons who do not have the computer equipment required to receive it directly. In any case, it may be useful to listen to the audio while following the written text as well, since learning is most effective when material is both seen and heard.

Topics discussed include new antiretrovirals (especially efavirenz), protease inhibitors and how to use them, hydroxyurea, when to start antiretroviral treatment, HIV treatment during pregnancy, more sensitive viral load tests, viral resistance testing, post-exposure prevention, the possibility of less aggressive antiretroviral approaches, adherence issues, twice daily and even once-daily antiretroviral dosing regimens, body-shape changes and metabolic disorders, salvage therapy, cost-effectiveness of antiretroviral treatment, underserved populations, access to care, prevention of mother-infant transmission, and the need for experienced physicians in quality HIV care.

Both the written transcript and the audio program are available at http://hopkins-aids.edu/geneva/info.html.



Viral Load: Roche Applies for Marketing Approval for UltraSensitive Test


On June 26 Roche Molecular Systems, Inc. applied to the FDA for permission to market a more sensitive viral load test. The test that is commercially available today can reliably quantify viral load to as low as 400 copies per milliliter of plasma; the new method extends this limit of quantification to 50 copies. The new test, called the Amplicor HIV-1 Monitor™ UltraSensitive Method, is actually an optional specimen processing procedure used with the currently available test (the Amplicor HIV-1 Monitor).

At the recent Geneva conference, a widespread consensus emerged that physicians will want a test which measures below the current 400-copy limit; one reason is that patients who get to very low levels are likely to keep the virus suppressed for longer than those whose viral load is close to 400. However, in many cases it will be difficult to advise patients who have test results between 50 and 400, since there can be significant costs or drawbacks to changing antiretrovirals.

Many physicians are already using the more sensitive viral load tests; the Roche UltraSensitive method has been available to researchers in the U.S. since February 1997. Commercial approval will reduce problems of access to a test which is now widely agreed to be useful.



IHV 1998 Annual Meeting (Gallo Lab Meeting)

August 23-29 in Baltimore


The annual meeting of the Institute of Human Virology -- traditionally known as the "Gallo lab meeting" -- will take place August 23-29 in Baltimore. Almost 200 oral presentations will report advances in the basic sciences of HIV infection, cancer, and hepatitis; most are highly technical as they are intended for scientists working in related fields. This year's meeting will be videotaped.

Program, registration, and other information is on the Web site of the Institute of Human Virology, http://www.ihv.org. Or you can call Jeff Meshulam, 410-706-8614.



Geneva Update Town Hall Meeting

August 17, Redwood City, California


The AIDS Community Research Consortium and other HIV/AIDS support organizations in San Mateo County will present a report on the recent 12th World AIDS Conference, with a focus on viral resistance, women and HIV, and cross-cultural perspectives. It will be held Monday August 17 from 6:00 p.m. to 8:30 p.m. at the Fair Oaks Community Center in Redwood City, about 25 miles south of San Francisco.

Admission is free. To reserve a seat, call 650-364-6563 by August 13.



San Francisco: Employment-Issues Training for Service Providers

August 19


A free, one-day training on employment issues for San Francisco AIDS service providers, vocational counselors, and job placement specialists will be held Wednesday, August 19, 9 a.m. to 4 p.m. at the UCSF Laurel Heights Conference Center, 3333 California St., San Francisco. Topics include benefits issues, psychological aspects, job search training, and vocational rehabilitation and training resources.

Persons interested are asked to register by August 12. Contact AIDS Benefits Counselors, 415-558-9845, fax 415-703- 9942.



AIDS Meals and Nutrition Conference

Sept. 10-13, San Francisco


The 5th annual AIDS Meals and Nutrition Providers Conference, "Food Fight 98: Combating HIV Through Nutrition", will be held September 10 through September 13 in San Francisco at the Sir Francis Drake Hotel.

Keynote speakers are Drs. Paul Volberding and Molly Cooke. Workshops include care for pregnant women, pediatric assessments and interventions, dietary strategies to maximize treatment efficacy, body composition and maintaining lean muscle mass, and information about administration and development of food-service programs.

The conference is sponsored by AIDS Nutrition Services Alliance (ANSA), in Washington D.C. For conference and registration information contact Cari Napoles, Conference Coordinator, c/o Project Open Hand, 730 Polk Street, San Francisco, CA 94109; phone 415-447-2471, fax 415-447-2493, email cnap@openhand.org.



Rural AIDS Conference

September 10-12, Albuquerque


"The Southwestern Conference on Rural HIV/AIDS: Issues in Prevention and Treatment," sponsored by the National Rural Health Association (NHRA), will take place September 10 through September 12 at the Hyatt Regency Hotel, Albuquerque, New Mexico. Scheduled speakers include: Sandra Thurman, Director, Office of National AIDS Policy; and R. Scott Hitt, M.D., Chair, Presidential Advisory Council on HIV/AIDS. Registration deadline is August 28; some scholarships are available.

For more information contact the NRHA: phone 816-756-3140, fax 816-756-3144 email mail@nrharural.org, or see the Web site at http://www.NRHArural.org/pagefile/eo.html.



Hepatitis C Conference

August 23-25 in Oakland


The HCV Global Foundation Second International HCV Conference, "The Silent Epidemic of Hepatitis C," will take place August 23-25 at Oakland Marriott City Center, Oakland, California. This meeting is intended both for patients and healthcare professionals.

For more information, call HCV Conference, c/o KREBS Convention Management Services, 415-920-7000, fax 415-920- 7001.



Medical Marijuana: Healing Alternatives Begins Distribution

by John S. James

Healing Alternatives Foundation, one of the oldest and largest AIDS buyers' clubs, will begin medical marijuana distribution on August 5.

John Salvati, Healing Alternatives general manager, described this program to AIDS Treatment News:

  • To protect the physicians, they will not be asked to either prescribe or recommend marijuana for their patients. The physician cannot decide whether or not a patient can receive the drug through this program; that decision will be made by Healing Alternatives.

  • Instead, physicians will be asked to acknowledge that they are aware that their patient is using marijuana for medical treatment, and that they will continue to provide treatment with knowledge of that use.

  • The treating physician will also be asked to confirm the diagnosis of the serious or life-threatening condition for which the patient is seeking access to the drug. Healing Alternatives will only accept conditions for which medical marijuana is recognized.

  • All batches will be tested for microbiological contamination.

  • Healing Alternatives, which is a non-profit community-based organization, will return any profits to the community and fully disclose where that money is going. If they are able to obtain donated marijuana, they will distribute it without charge.

The following intake procedure will be used:

  • All intake will be at the Castro Street office during regular hours. (No marijuana will be dispensed or stored at this office, however.)

    The first step is the physician's letter. Healing Alternatives is using a draft created by the San Francisco Department of Public Health for physician use; however, to protect the doctor, Healing Alternatives removed one sentence, in which the physician "recommends" cannabis use for the patient. This letter may be either on the form provided by Healing Alternatives, or on the physician's letterhead.

    In either case the physician certifies that the patient is under his or her care for the treatment of ___; that he or she has discussed the medical benefits and risks of cannabis use with the patient as a treatment for these medical conditions; and that if the patient chooses to use cannabis therapeutically, the physician will continue to monitor the patient's medical condition and to provide advice on his or her progress. The statement also notes that the letter is for the use of the patient and Healing Alternatives Foundation only (not other marijuana distribution programs), that the physician may be contacted to verify the information in the letter, and that the patient authorizes the physician to discuss his or her medical condition and the contents of the letter with the center for verification purposes only. The statement is signed by the patient and physician, dated, and expires after a time period specified by the physician.

    When the form is returned, the patient can join Healing Alternatives; the annual membership fee is $10 to $35 for persons in the medical-marijuana program, which includes a contribution to a legal defense fund. After an intake process, it takes about a week for Healing Alternatives to verify the paperwork.

    Financial need can always be taken into account.

Healing Alternatives is located at 505 Castro Street (at 18th Street), 2nd floor; phone 415-626-4053. It is open Tuesday through Friday from 12 noon to 6 p.m., and on Saturday from noon to 5. Healing Alternatives sells selected nutritional supplements, provides referrals, and distributes AIDS/HIV treatment information.



Nutritional Supplements: Call for Information

by John S. James

AIDS Treatment News is planning more coverage of nutritional supplements used or potentially useful for persons with HIV. We would like to hear from readers about what has or has not helped them. We also welcome any comments on some of the ethical and credibility issues of reporting in this area.

  • We are most interested in what you have learned from personal experience (either your own, or of persons you know). Are you convinced that any particular supplement or program has helped you, or a friend or other associate -- or has failed to help -- or has been harmful in some way?
Let us know what you used (including how much, and how long), why you tried it, and why you think it did or did not work for you. Email or call John S. James, aidsnews@aidsnews.org, or 415-255-6259. Some of the difficulties in reporting on nutritional supplements are:
  • U.S. culture draws a sharp line -- probably too sharp -- between "foods" and "drugs." Not all cultures do; for example, there are Chinese restaurants where you can order by describing certain ailments to the cook, who will prepare a meal accordingly. In the U.S. they have needed to keep a low profile, making a potentially fascinating and useful area difficult to find or study.

  • The food/drug divide has hurt research on both sides. Nutritional research has often been ignored or greatly underfunded. On the drug side, great sums are spent on poorly designed research shaped by regulatory and promotional purposes -- especially clinical trials that look only or primarily for statistically significant differences between averages, while ignoring mechanisms of action, how and why patients differ from each other, and who should or should not be using the drug. (And a major but seldom-noted element of the cost of medical care is that only expensive potential remedies are likely to be developed, since they can finance careers -- even when cheaper approaches may be safer and more appropriate.)

  • Because nutritional supplements have less research data than drugs while at the same time being more accessible, the community of users is often well ahead of the academic world in understanding their use. The lack of data, and the disagreements among experts, can make reporting difficult.

  • Sometimes the leading expertise on nutritional supplements is in the sports world, especially body building. HIV/AIDS uses may be similar or may be different.

  • The supplements industry has become a money machine, with far less government scrutiny over promotional statements than applies to the pharmaceutical industry. It is hard to distinguish the credible from the hype.
Where hard news is lacking, we may only be able to outline plausible possibilities, which people may try to see what works for them.



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.




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