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AIDS Treatment News
November 6, 1998

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Contents:


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T-20 Results Published

by John S. James


Complete results on the first multi-dose human trial of T-20 were published November 2 in Nature Medicine1 with an accompanying editorial.2 In summary:

  • At the highest dose tested, patients treated with T-20 alone had a viral load drop of 1.96 logs in 14 days. Analysis of viral dynamics shows that the drop was limited to two logs because the trial only lasted 14 days (since it takes the body that long to clear 99 percent of HIV from the blood, even if new production is completely shut off).

  • All four patients at the highest dose of T-20 had remarkably similar viral decay dynamics -- which appeared to be better than those observed in other trials with triple-drug HAART therapy, and almost as good as a trial of four-drug HAART therapy with treatment-naive patients. (Three of the four in the T-20 trial were treatment naive; the fourth had been treated but had been off other antiretroviral therapy for at least 14 days.)

  • None of the 16 volunteers had to be taken off T-20 because of adverse effects or toxicity. A few had possible side effects such as fever or headache, but these did not appear to be drug related.


Comment

This trial was first reported over a year ago (September 16), at the IDSA (Infectious Diseases Society of America) meeting in San Francisco3; we summarized that presentation in AIDS Treatment News issue #279, September 19, 1997. Unfortunately that report received little public attention, for several reasons. The technical details have not been published until now; the drug's mechanism of action is new and difficult to understand; the sponsoring company (Trimeris, Inc., in Durham, North Carolina) was in a "quiet period" at the time of the conference and could not publicize the results; and there were very few treatment activists at that particular conference.

In this trial T-20 was administered intravenously twice a day. It is likely that the drug can be administered more efficiently subcutaneously, by a portable computerized infusion pump, like the pump widely used in diabetes treatment to administer insulin.

This study has clearly established proof of principle for a drug with an entirely new mechanism of action (which means, among other benefits, that no cross-resistance is expected between T-20 and any treatment now in use). Viral resistance to T-20 does occur; it is not known how much problem it will cause in practice. It is possible that resistance might be managed by using T-20 to shut off viral replication almost completely -- since blood levels can be much higher than necessary to prevent replication, and the infusion pump eliminates food, absorption, and peak-trough issues, and should greatly improve adherence. Other possible approaches for managing resistance include combining T-20 with other antiretrovirals, or creating a new version of T-20 to target the resistant virus.

A new trial, TRI-003, is currently recruiting and about half filled as we go to press (see AIDS Treatment News #300, August 7, 1998). It will obtain longer-term viral suppression data, and verify dosage for the infusion pump. It will also check to see if the body produces antibodies against T-20 -- which might or might not be a problem in long-term use.

Currently T-20 is difficult to produce in large quantities. But there is little doubt that efficient manufacturing methods can be developed.


References

  1. Kilby JM, Hopkins S, Venetta TM, and others. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nature Medicine. November 1998; volume 4, number 11, pages 1302-1307.

  2. Richman DD. Nailing down another HIV target. Nature Medicine. November 1998; volume 4, number 11, pages 1232- 1233.

  3. Saag M, Alldredge L, Kilby M and others. A short-term assessment of the safety, pharmacokinetics, and antiviral activity of T-20, an inhibitor of gp41 mediated membrane fusion. IDSA 35th Annual Meeting, San Francisco, September 16, 1997 [abstract #771].



U.S. Testosterone Shortage: Call for Information

by Tadd Tobias and John S. James


There is a nationwide shortage of certain injectable testosterone products. At this time we do not know how serious the problem is.

  • Generic testosterone cypionate has been unavailable for weeks in San Francisco, and presumably throughout the U.S. (although some stocks may still remain). No one is currently manufacturing generic testosterone cypionate or enanthate for the U.S. market, and there are no immediate plans to resume production.

  • Testosterone enanthate, according to two leading HIV physicians we contacted, is basically equivalent to testosterone cypionate and can be substituted for most patients (rarely someone may be allergic to one but not the other). Generic testosterone enanthate is currently in stock in many pharmacies, but shortages are expected. One San Francisco physician has had no problems prescribing it, with patients filling their prescriptions at pharmacies. But another physician, whose managed-care contract requires that he inject the drug in his office, has been unable to obtain supplies even after calling distributors around the country; he has also had problems obtaining nandrolone decanoate, an anabolic steroid.

  • If the generic drugs are unavailable, physicians can use brand-name versions, which cost several times as much -- or switch to other expensive options such as one of the testosterone patches, (Androderm® or Testoderm®) or the oral anabolic oxandrolone (Oxandrin®). At least one non-generic testosterone product -- Depo-Testosterone® 200mg/10mL -- has been back-ordered since September 28. A brand of testosterone enanthate -- Delatestryl® -- is available, with no supply problems expected. The same is also true for the testosterone patches whose manufacturers have told AIDS Treatment News that ample supply is available.

  • The additional expense is especially problematic for HIV physicians under certain managed-care contracts. Even in San Francisco, some leading HIV specialists have been forced into contracts with no AIDS "carve out" -- which means they are paid about $5 per month to cover office visits for a person with AIDS, the same as for a healthy middle-aged adult. The additional reimbursement for a testosterone injection barely covers the cost of the medicine for the cheapest generics. Many physicians who specialize in AIDS care are losing money on every patient and being forced to pay for their AIDS practice by taking on other work; they have no margin to cover the sharply increased cost of non-generic testosterone.


How the Shortage Happened

On September 10, 1998 the FDA moved against Steris Laboratories, Inc. (a division of Schein Pharmaceutical, Inc.), seizing large stocks of their drugs and ordering a halt in further production of all products at that facility; Steris, located in Phoenix, Arizona, laid off about 350 workers. The FDA has not said that any of the drugs are bad, but that the company had not followed required procedures for documenting quality assurance.

Steris had been manufacturing all the generic testosterone cypionate and enanthate sold in the U.S., even that which is sold by other companies.

On October 16, 1998, a "Consent Decree of Condemnation and Permanent Injunction" between the FDA and Steris allowed the company to resume distribution of some but not all of its products. The consent decree (which is public information) includes an "Exhibit C" of drugs which the FDA has determined are medically necessary. Steris will re-test the seized stocks of these drugs, and return them to the market if possible; also, it will resume manufacturing, when permitted, for these products. However, Exhibit C does not include any form of testosterone, apparently because the FDA believed that enough other companies were marketing equivalents of the drug; the FDA has approved about three dozen testosterone preparations of about a dozen different companies, but at this time does not know how many are currently on the market. Exhibit C also includes chorionic gonadotropin 5,000 U/vial and 10,000 U/vial (sometimes used to help restart endogenous testosterone production after discontinuation of testosterone therapy) and nandrolone decanoate 100 mg/mL and 200 mg/mL -- suggesting that if any shortages of these drugs develop, they should be temporary.

Steris did list testosterone cypionate and enanthate 200mg/mL in Exhibit A (drugs it wants to resume manufacturing when possible). It lists a lower concentration of both testosterone cypionate and enanthate (100mg/mL) -- and also nandrolone decanoate 50mg/mL -- in Exhibit B (products it may withdraw from the market).


Call for Information

We have been told that no generic testosterone cypionate or enanthate is currently being manufactured for U.S. sale. Pharmacies and distributors may have inventory of enanthate, and manufacturing may be resumed. Most of the non-generics should remain available. If you have any additional information about supply of generic testosterone, non-generic testosterone, nandrolone, other anabolics, or chorionic gonadotropin, please let us know; contact Tadd Tobias at AIDS Treatment News, 415-255-0836 or ttobias@aidsnews.org.



Abacavir (ZiagenTM) Approval Recommended


On November 2 the FDA Antiviral Drug Products Advisory Committee recommended accelerated approval of abacavir (brand name Ziagen). The vote was 7-2.

The most important trial compared abacavir plus AZT plus 3TC vs. indinavir plus AZT plus 3TC. In preliminary analysis at 16 and 24 weeks, the two groups looked very similar. This study is still blinded, so it is not known which group is receiving which combination.

Extensive information about this drug will be available in a transcript of the meeting, which will be placed on the FDA Web site. For instructions on finding the transcripts there, see "Abacavir (ZiagenTM) Advisory Committee Meeting, November 2," in AIDS Treatment News #304, October 2, 1998.



Advertisement

Induction/Maintenance Strategy Failed in U.S., French Trials


Two similar trials, one in the U.S. and one in France, tried switching patients to less-intensive treatment after triple combination therapy had reduced viral load to a relatively low level. In both cases, viral load returned more often in the patients who were switched to the less intensive regimens, than in those who remained on three drugs. But even for those switched to the less-intensive regimens, a majority did not have their viral load return by the time the study was stopped.

In both trials, the patients started with indinavir (Crixivan®) plus AZT plus 3TC. In the U.S. study, they were randomized to either continue triple therapy, or switch to AZT plus 3TC, or to indinavir alone. In the French study, they were randomized to either continue triple therapy, switch to AZT plus 3TC, or switch to indinavir plus AZT.

Both trials were first presented as late breakers at the 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998. The full papers for both,(1,2) plus an editorial,(3) were published October 29 in the New England Journal of Medicine.


References

  1. Havlir DV, Marschner IC, Hirsch MS and others. Maintenance antiretroviral therapies in HIV-infected subjects with undetectable plasma HIV RNA after triple-drug therapy. New England Journal of Medicine October 29, 1998; volume 339, number 18.

  2. Pialoux G, Raffi F, Brun-Vezinet F, and others. A randomized trial of three maintenance regimens given after three months of induction therapy with zidovudine, lamivudine, and indinavir in previously untreated HIV-1- infected patients. New England Journal of Medicine October 29, 1998; volume 339, number 18.

  3. Cooper, DA. Therapeutic strategies for HIV infection -- Time to think hard. New England Journal of Medicine October 29, 1998; volume 339, number 18.



Efavirenz (SustivaTM) Available through Patient Assistance Program


Several states, including California, Pennsylvania, and New York, have not yet added efavirenz (Sustiva) to their AIDS Drug Assistance Program (ADAP) formulary, due to concern that a new wave of high drug prices could make it impossible to assure uninterrupted supply of important medications. DuPont Pharmaceuticals has assured the community that people who need the drug will not be denied it. The company, like most large companies in the pharmaceutical industry, has set up a patient assistance program to locate possible sources of reimbursement, and if necessary provide the drug to persons who have no other way to pay for it.

For information about this program, physicians and patients can call 800-334-4486.



Amprenavir (AgeneraseTM) Submitted for Approval


On October 16 Glaxo Wellcome announced that it has submitted the new protease inhibitor amprenavir (brand name Agenerase) for U.S. drug approval; four days later it also filed for approval in Canada and in Europe. Amprenavir was developed by Vertex Pharmaceuticals Incorporated, and will be marketed by Glaxo Wellcome under a partnership between the two companies.



National AIDS Treatment Advocates Forum

December 5-8, Philadelphia


The National AIDS Treatment Advocates Forum will be held this year from December 5-8, at the Crowne Plaza Philadelphia Hotel. It is being organized by the National Minority AIDS Council with the support of eight other AIDS service, information, and research organizations. The registration fee after November 9 is $175.

This year's program will be organized in three conference tracks: Clinical Research and Drug Development; Research Policy and Legislation; and Treatment Education and Advocacy.

For more information, contact Oscar Lopez, 202-483-6622x327, or olopez@nmac.org.



Glasgow Conference Reports on Web


The 4th International Conference on Drug Therapies in HIV Infection will take place in Glasgow, Scotland, November 8-12. Those who cannot go can find information on the Web:

  • Extensive next-day summaries which will be posted on the Web site of Healthcare Communications Group, http://www.healthcg.com/hiv. Written by well-known experts, these summaries will remain on the Web for about a year, so you can read them any time, not only during the conference. CME credit will be available for physicians, nurses, and pharmacists, but anyone can use the material for their own education.

  • The National AIDS Treatment Advocacy Project site, http://www.natap.org, will carry summaries by NATAP founder Jules Levin.

There may be other Web coverage as well.



Lipodystrophy, Anemia, Resistance, Other Articles at www.healthcg.com/hiv


Recent articles on the Healthcare Communications Group Web site include:

  • Update on Lipid Abnormalities and Cardiovascular Complications in HIV Infection, by Donald P. Kotler, M.D., posted October 20;

  • Current Management of Antiretroviral Therapy in the HIV- Infected Patient, posted September 28;

  • Quick Reference Guide to Antiretrovirals, by Malte Schutz, M.D., posted October 27;

  • The Importance of Treating Anemia in Disease, by Ronald Mitsuyasu, M.D., posted September 30;

  • AIDS Related Lymphoma, by Alexandra Levine, M.D., posted October 29;

  • PCP, Toxoplasmosis, and HSV: Management in HIV Disease, by Richard Chaisson, M.D. and William Bishai, M.D., Ph.D., posted October 26, 1998;

  • Plus a review of recent data on resistance to antiretrovirals, and a survey on physician use of the Internet, in the October issue of Healthcare Communications Group's Online Journal.

For more information about the Healthcare Communications Group Web site, http://www.healthcg.com/hiv, contact Edward King, eking@healthcg.com.

Note: On October 29 Medscape announced that it is acquiring Healthcare Communications Group. Medscape runs a free site, http://www.medscape.com, which currently has 800,000 registered members, including 150,000 physicians; the Medscape site has 18 specialty home pages, including one on AIDS.

Users of the Healthcare Communications Group site should not be affected, since a major purpose of the merger is to apply that site's approach to other Medscape specialties as well. Medscape CEO Paul Sheils explained the thinking behind the merger: "Physicians are among the busiest professionals in the world. They need fast, practical answers to their tough clinical questions; and they rely on experts to tell them quickly and succinctly about the latest developments and new drug therapies. Clinicians require access to that critical information from wherever they are: the office, the hospital and home. Everything we do at Medscape is designed to satisfy those fundamental needs. By combining the comprehensive, original state-of-the-art programs from HCG with the depth and breadth of Medscape's comprehensive databases, into an easy-to-use, free site, accessible from any browser anywhere, we are able to provide physicians with the tools they need to get those answers fast and stay on the cutting edge of medicine."

[AIDS Treatment News is publishing a series of short articles on major AIDS treatment Web sites, focusing on important new material on each. All these sites can be reached from the AIDS Treatment News link site, http://www.aidsnews.org; you only need to remember "aidsnews.org" to get to any of this information.]



New TB Guidelines for Persons with HIV


On October 30 the U.S. Centers for Disease Control announced published guidelines for prevention and treatment of tuberculosis in persons with HIV. Some highlights of the current guidelines:

All persons with HIV should be screened for tuberculosis, and treated if necessary.

The TB drug rifampin should not be used together with protease inhibitors or non-nucleoside reverse transcriptase inhibitors, because it can seriously impair the effectiveness of those antiretrovirals. But another TB drug, rifabutin, can be used with antiretroviral treatment.

There is now a two-month preventive treatment for persons who have been infected with tuberculosis, as an alternative to the traditional one-year isoniazid regimen.

Copies of the document can be obtained by calling 404-639- 8063, or from various Web sites including http://www.healthcg.com/hiv.



Alitretinoin Gel (Panretin®)

FDA Hearing November 16


On November 16, the FDA Oncologic Drugs Advisory Committee will consider a new drug application for alitretinoin (brand name Panretin), for first-line topical treatment of Kaposi's sarcoma lesions. For more information about this meeting, call the FDA Advisory Committee Information Line, 800-741-8138, and when requested, enter the number 12542.



Record AIDS Funding from Outgoing Congress

by John S. James


AIDS funding received large increases for fiscal year 1999 (which started in October 1998). According to numbers provided by the AIDS Action Council:

  • $110 million was budgeted to fight the AIDS epidemic in African-American communities, and to reduce racial and ethnic disparities in AIDS programs.

  • The Ryan White programs received a $261.4 million increase -- including a $175.5 million dollar increase for ADAP, the need projected by the ADAP Working Group (before the current moves to increase drug prices, however).

  • AIDS research at the U.S. National Institutes of Health was increased by $184.9 million; overall NIH funding for medical research was increased by at least as large a proportion.

  • Substance abuse prevention and treatment was increased by $297 million.

  • AIDS prevention was increased by $32.9 million, which includes $10 million for HIV screening of newborns.


Comment

The success of AIDS funding in this Congress was due to several lucky conditions, not all of which will be repeated. The federal government had an unexpected surplus, our legislative advocates were in place, and they could call on the community for grassroots support. But also, this Congress was heavily distracted by other affairs, and with money on its hands, threw it at a lot of things and went home. It would be a serious mistake to count on good fortune in the future. Instead we need to broaden our focus, and work more with other health constituencies.

On non-funding issues, AIDS-related legislation was mostly negative or mixed. Congress not only prohibited Federal funding of needle exchange for an additional year, it also included language which threatens Federal funding for any organization which conducts needle exchange, even with private dollars. And it prohibited the local Washington D.C. government from funding needle exchange there.

On another issue, the Senate confirmed the new FDA commissioner, Jane Henney. According to Biocentury Extra (October 22), she was confirmed moments before the Senate adjourned, and only after she had promised in writing not to seek a manufacturer of RU-486, (the "abortion pill" which may also be useful in treating breast cancer and other diseases).

Also in its last-minute rush, Congress passed a law to federally regulate content of the Internet, to prevent pornography from reaching children. We do not yet know if it could threaten AIDS prevention information.


Medical Marijuana

On medical marijuana, Congress passed a compromise resolution requiring the FDA to report in 90 days on efforts to have marijuana considered for approval as a prescription drug. This is progress, and the original resolution was much worse, as it would have put Congress on record as opposing medical marijuana entirely.

But we are concerned that the FDA is not set up to consider this issue well. The FDA institutionally favors chemical entities over plant parts, and drug approval typically requires studies taking years and costing millions of dollars -- a largely pointless exercise when trying to measure subjective relief. Who will produce such data for marijuana? What is needed instead is flexibility now in letting patients find the relief that works for them -- while researchers isolate and develop the (probably non-psychoactive) cannabis ingredients which are now suspected of providing much of the medical benefit of the plant. Eventually these will be developed as conventional new drugs, and in rich countries at least the need for medical marijuana will largely go away.

The outgoing Congress had other ideas. It nullified in advance the November 3 Washington D.C. vote on medical marijuana, by forbidding the city's local government from spending any money to count the votes or certify the result; the ballots had already been printed, however, and we have heard that the votes will be counted automatically, although the election result cannot become law. Congress also authorized money to biologically engineer a fungus to destroy marijuana plants.



Help Wanted, AIDS Treatment Writer, New York


Treatment Issues, the AIDS treatment newsletter published by Gay Men's Health Crisis in New York, urgently needs a new associate editor to start as soon as possible.

"The ideal candidate will have a history of writing medical news articles and being familiar with AIDS treatment activism. A demonstrated ability to translate complicated pharmaceutical and medical data into popular language is essential. Salary is in the high 30s. Send applications, including resume, writing samples, and salary requirements, to CJ Bacino, Human Resources Dept., Gay Men's Health Crisis, 119 W. 24th St., New York, NY 10011 (fax: 212-367-1527)."



California: Medicaid Expansion Needs Quick Attention after the Election

by John S. James


Medicaid, the government program for medical care for persons with low income, is today the largest provider of healthcare for persons with AIDS. But to be eligible for Medicaid, a patient needs not only a low income, but also an official diagnosis of "disability"; therefore persons with HIV who need medical care cannot get Medicaid, no matter how low their income, until they first get sick enough to qualify. It would certainly be better for them, and it may also cost less money, to start treatment earlier, before their illness has progressed enough that they are officially disabled.

Vice President Al Gore took the lead in considering Medicaid expansion nationwide for persons with HIV. It did not happen, however, because it could not be proved to cost no more than the present system. Meanwhile, individual states can implement this policy in their own Medicaid systems.

In California, a serious Medicaid-expansion effort was underway in the office of outgoing Republican Governor Pete Wilson, at the initiative of several AIDS organizations. The new Democratic governor, Gray Davis, is expected to be sympathetic. But it is important that the new administration hear from the AIDS community early, that this issue is important to us. A successful program in California would be very helpful in gaining similar access to care in other states, or in the U.S. as a whole.



Youth Consent, Confidentiality for Counselors

San Francisco December 1


Two nationally recognized experts will speak on the often-problematic task of maintaining confidentiality when counseling young clients under California laws. Therapists are required to call law enforcement in some cases -- if the minor has sex with an adult, for example -- whether or not that is in the interest of the client. Also, parental consent is sometimes required.

Addressing such issues will be Erica Monasterio, F.N.P., associate clinical professor, University of California San Francisco Division of Adolescent Medicine, and Catherine Teare, M.P.H., health policy analyst, National Center for Youth Law. This program is sponsored by Health Initiatives for Youth.

The seminar will be held Tuesday, December 1, 2:00 p.m. to 4:30 p.m., at San Francisco State University Downtown Center, 425 Market Street, 2nd floor (at Fremont Street), rooms 8 and 9. There is no charge, but space is limited and you should reserve a place by calling Helen at Health Initiatives for Youth, 415-487-5777, ext. 17, by November 23, 1998.



California ADAP Update


Our last issue explained in detail a problem with the California ADAP (AIDS Drug Assistance Program), which led to many people being surprised when the central computer said they were no longer eligible after September 1. They still are eligible (unless their income is now too high, or they otherwise do not meet the criteria); however, Federal rules require that they re-establish eligibility every year, and few counties or other ADAP jurisdictions informed people when their year was up. (The reason for the sudden surge of rejection notices in September is that the California system was gradually centralized about a year ago, and for many clients the one-year clock had to be reset at that time because of database problems in the earlier, non-centralized records.)

Another California wave of expiration notices is expected in early November. However, the ADAP system has been revised to make it easier for pharmacies and patients to deal with this problem. Also, pharmacists are more familiar with it than they were a month ago.

If your one-year period has expired, you should be asked by the pharmacist to sign a form which gives you notice that you must re-apply within the next month; then the pharmacist can release a 30-day emergency supply of the drugs. Then within 30 days, you must re-apply at an ADAP enrollment center, which can involve some paperwork. In theory it does not matter which center you apply at, but in fact some eligibility workers are easier to work with than others; it may help to get a recommendation if possible from a friend or advisor.

If you need to apply or re-apply for California ADAP, we suggest reading "California ADAP Alert," in AIDS Treatment News #305, October 16, 1998. There has been one change, however. Since that article was published, the ADAP computer system has been changed, at least temporarily, so that you can no longer check your own eligibility status. The reason for this change is concern about privacy and confidentiality, an issue now being reviewed.

If you need assistance with California ADAP, call PMDC, 888-311-7632. You can reach an Enrollment and Eligibility Specialist Monday through Friday 9 a.m. to 7 p.m., Saturday 9 a.m. to 5 p.m., and Sunday 11 a.m. to 4 p.m.



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.

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!




  
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