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T-20: New Trial Enrolling, 9 U.S. Citiesby 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.
CommentTrimeris 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 InformationFor 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 NIHby 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.
CommentInterest 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 InformationFor more information about volunteering for this study, contact either Tino Merced-Galindez, R.N. (800-772-5464 ext. 562, or 301-496-8959, or firstname.lastname@example.org), or Richard Little, M.D. (800-772-5464 ext. 657, or email@example.com), at the HIV and AIDS Malignancy Branch, National Cancer Institute.
Ritonavir Capsule Manufacturing Problems Will Require Switch to Liquid Formulationby 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- According to Abbott, all the capsules which have been shipped
to pharmacies and distributors are OK.
The price of the drug should be about the same for either
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
"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
"The following conversion equation may be helpful:
"6 Norvir capsules (100 mg each) = 7.5 mL of Norvir liquid (1
"4 Norvir capsules (100 mg each) = 5 mL of Norvir liquid (1
According to Abbott, all the capsules which have been shipped to pharmacies and distributors are OK.
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:
"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:
"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)."
Geneva Medical Report Now on Webby 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
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
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
Admission is free. To reserve a seat, call 650-364-6563 by August 13.
San Francisco: Employment-Issues Training for Service Providers
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
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 firstname.lastname@example.org.
Rural AIDS Conference
September 10-12, Albuquerque
Hepatitis C Conference
August 23-25 in Oakland
For more information, call HCV Conference, c/o KREBS Convention Management Services, 415-920-7000, fax 415-920- 7001.
Medical Marijuana: Healing Alternatives Begins Distributionby 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:
The following intake procedure will be used:
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 Informationby 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.
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.