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AIDS Trestment News
July 2, 1999

Contents:


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Ritonavir (Norvir®) Capsules Back: Refrigeration Optional


As this issue went to press, Abbott announced that its reformulated ritonavir capsules have been approved. The new capsules must be refrigerated until dispensed to patients; then "refrigeration by patients is recommended, but not required, if used within 30 days and stored below 77 degrees Fahrenheit." The capsules are used twice daily with food.



Organ Transplants: One Million Dollars for Research

by John S. James


The California budget for fiscal 1999-2000, signed into law on June 29, includes $1,000,000 "for liver and kidney transplant research for people with HIV, which will permit the San Francisco campus [of the University of California] to examine organ transplants treatment options for individuals with HIV."

Although it will take place in San Francisco, this research is important to everyone. People with HIV have been almost entirely excluded from organ transplants, and many have died as a result. Meanwhile, perfectly good livers are thrown away because the donor is believed to be gay, and therefore conceivably infected too recently to be detected on tests. Much of this exclusion is a carry-over from early days before effective treatments; other factors are prejudice, surgeons' fears that they could become infected while performing the operation, and medical uncertainty about such issues as possible interactions between antiretrovirals and the immune-suppressive drugs used after transplantation. The new research funding may help to end the most deadly discrimination against persons with HIV -- and advance knowledge of transplantation and the immune system, for everyone's benefit.

Credit for this victory goes to ACT UP/Golden Gate (especially Jeff Getty), and to Assemblywoman Carole Migden of San Francisco, who moved the measure through the budget process in the legislature. A similar measure last year was vetoed by then-governor Pete Wilson.



Immune Reconstitution: New Review on Web

by John S. James


"Immune Reconstitution and Immunotherapy in HIV Infection," an excellent one-hour overview of current knowledge about possibilities of immune-based therapy for HIV disease, went online last week on the Medscape site, http://hiv.medscape.com; the author is Bruce D. Walker, M.D., of Massachusetts General Hospital and Harvard Medical School. Anyone can use this review without charge, and for medical professionals, one hour of continuing medical education credit is available. This module is written for "primary-care physicians, physician assistants, pharmacists, as well as specialists in AIDS care who seek a better understanding of host defenses against HIV and how these might be augmented to benefit patients." Readers will need some familiarity with basic immune-system concepts and terminology -- for example humoral (antibody) vs. cellular immunity, CD4 T-helper cells, and CD8 CTLs (cytotoxic T lymphocytes). For those who want more in-depth information, over 130 references are included.

We believe that studying the immune system in HIV disease -- and the possibility of therapy to help the immune system maintain control of the virus -- is the most important area of AIDS treatment research today, but receives too little attention and funding because the money and institutional structures are focused on antiretrovirals. Dr. Walker is one of the most influential experts in this area. To give readers a quick overview of his review of this field, we quote the introduction, table on contents, and a paragraph on testing for HIV-specific immunity.


Introduction

"An understanding of the potential for immunotherapy and immune reconstitution in HIV infection requires a detailed understanding of the host immune response to this virus. Emerging data over the past 2 years indicate that the immune system plays a key role in determining the viral set point and delaying disease progression. There is no doubt that highly active antiretroviral therapy (HAART) has had a beneficial effect among infected persons,(1,2) but in the absence of the ability to eradicate latent virus, it is likely that the next big breakthroughs in HIV treatment will come through manipulation of the immune system. Therefore, this review begins with a detailed explanation of the way in which the body responds immunologically to chronic viral infections in general and to HIV in particular, and provides a description of the most important components of this immune response for containing the virus. Specific Immunotherapeutic strategies that are being pursued or planned will then be discussed."


Table of Contents

Introduction
Immune Protection in Chronic Viral Infections
Immune Responses to HIV-1 Infection
Immunologic Control of HIV Infection

     Cytotoxic T lymphocytes
     T-helper cell responses
     Neutralizing antibodies
     The special case of exposed seronegative persons
Limits of Immunologic Control
     Immune exhaustion
     Lack of adequate T-helper cell function
     Immune escape
     Host genetic factors
     Direct infection of CD8 cells
Immunologic Monitoring in HIV Infection
Immune Reconstitution in the Era of HAART

     General immune function
     Thymic function
     HIV-specific immunity
     Immune recovery inflammatory syndromes
Approaches to Immune-Based Therapy in HIV Infection
     Cytokine-based therapy
     Adoptive cell transfers
     Therapeutic vaccination
     Interruptions in therapy to augment immunity
     Passive antibody therapy
     Gene therapy
Conclusions
References


Tests of HIV-Specific Immune Function

Dr. Walker discusses new blood tests of how well the immune system is responding to HIV. Today these tests are used only by research specialists, but they could become more standardized and available -- greatly accelerating research and development in immune-based therapies, as viral load testing did several years ago for the development of antiretrovirals.

"Tests of virus-specific immune function, including CTL assays, assays for T-helper-cell function, and neutralizing antibody responses, are not readily available. In fact, there are no standardized tests in existence for measuring HIV-1-specific immunity. These assays are only available through research laboratories, and different investigators employ different techniques for performing them. The field would greatly benefit from standardized, sensitive and highly reproducible assays. These are likely to be forthcoming now that new flow-cytometry-based assays are becoming available, and may be extremely important in monitoring clinical trials of immune-based therapies."


Taking the Course Online (Or Printing a Copy)

Medical professionals or others can take this one-hour course at http://hiv.medscape.com; look under "Clinical Management." You can also print a copy to read elsewhere, directly through your browser with no other software required.

This program was sponsored by an unrestricted grant from Agouron Pharmaceuticals.



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Ribavirin for Hepatitis C: 80% Price Reduction Available July 9?

by John S. James


Ribavirin is used in combination with alpha interferon for treating hepatitis C; it is not effective alone. (Ribavirin was also tested as an HIV treatment years ago; we suspect that it probably would have been approved except for a bitter political dispute, and that it should be examined again for possible use as a component in modern HIV treatments.)

Ribavirin has been approved and widely used throughout the world for years, except in the United States, where it was not approved for oral use until June 3, 1998, in combination with alpha interferon for treating hepatitis C. Unfortunately, Schering-Plough got the FDA to approve an unprecedented "bundling" of the drugs, meaning that U.S. patients ordinarily cannot buy ribavirin unless they also buy Schering's brand of alpha interferon, called Intron A, both at a notably high price. (Outside the U.S., ribavirin can be purchased alone).

The different brands of alpha interferon are not identical, and doctors sometimes prefer one of the other forms available in the U.S. and approved for hepatitis C (currently Roferon, Infergen, and Wellferon, in addition to Intron A), but it has been hard to obtain the ribavirin for these combinations without also paying for the Schering product and throwing it away. The bundling problem may become even more serious when a new form of alpha interferon called Pegasys -- which maintains a more steady level in the bloodstream and may be a major improvement over standard alpha interferon for treating hepatitis C, at least as monotherapy -- is approved and becomes widely available.

Bundling also inhibits experimentation with ribavirin as a possible element in combination treatment for HIV, which could be important for certain patients whose virus has become resistant to many of the antiretrovirals available today. Although known as an antiviral, ribavirin may actually work by helping the immune system respond to certain infections, for example by reducing production of IL-4. Ribavirin does have serious side effects, including anemia.

On June 26 the Hepatitis C Action & Advocacy Coalition, a credible grassroots advocacy organization, announced that starting July 9, 1999, ribavirin would be available from a compounding pharmacy in Pittsburgh, Pennsylvania, at a price reduction of almost 80%. HAAC had learned that the patent on ribavirin expired July 8; in the U.S., however, Schering has an additional three years of exclusivity, meaning that the FDA will not approve any rival ribavirin during that time, regardless of its medical and pharmaceutical merits. But the FDA does not approve compounded medications -- so neither HAAC nor the pharmacy see any legal barrier to selling compounded ribavirin after the patent expires. Money talks, however, so no one knows what will happen July 9.

From HAAC Press Statement of June 26:

"Safe and Reliable Access to 'Unbundled' Ribavirin at 20% of Schering's Price

"Dear Members of the Hepatitis C Patient and Health Care Communities:

"HAAC is pleased to inform you that, beginning July 9, 1999 and barring any unforeseen difficulties, a safe and reputable alternative source of ribavirin USP will be available at 20% the cost of the drug when purchased from Schering-Plough. Fisher's Specialty Pharmacy Services (SPS) in Pittsburgh is compounding ribavirin USP by individual prescription. It is NDC # 63370-219-55, properly labeled, with a patient information leaflet that includes all known side effects, warnings and recommended precautions.

"The cost is $1.25/200 mg capsule. At the common dose of 1,200 mg a day, the monthly cost for ribavirin from Fisher's SPS will be only $225. This is 80% less than Schering's price of $1,040. Ribavirin has only been available packaged with Schering's interferon (Intron A) as part of the Rebetron kit.

"Fisher's will work with you and your insurance provider. Contact them at:

Fisher's Specialty Pharmacy Services 3904 Perrysville Avenue
Pittsburgh, PA 15214
Phone: (412) 231-3777
Toll Free Phone: (888) 347-3416
Toll Free Fax: (877) 231-8302

Web address: http://www.spsdrug.com

****

"The Hepatitis C Action & Advocacy Coalition is a national independent HCV patient advocacy group. We do not accept money from any pharmaceutical provider including those mentioned in this announcement. Our goal is to help put the control for treatment choice, access and flexibility back in the partnerships of physicians and patients."


For More Information

For more information, see http://www.HIVandHepatitis.com

For background on compounding, see AIDS Treatment News #320, June 4, 1999.

Hepatitis C Action & Advocacy Coalition can be reached through Brian D. Klein, HAAC_SF@hotmail.com.



Medical Marijuana: California Task Force Proposes Registration System; Hearing Set for July 13

by John S. James


A task force set up by California Attorney General Lockyer will propose that the State Department of Health Services "shall establish and maintain a voluntary program for the issuance of registry identification cards" to patients, to protect them and a designated caregiver from arrest under California law. (This state system cannot affect Federal law, but state law accounts for most medical-marijuana arrests.) Our understanding is that the program is "voluntary" in that it would not prevent those who do not have the cards from seeking protection in court through California's Proposition 215 -- the medical-marijuana initiative passed by the voters, but not implemented because of unrelenting hostility from the state's previous governor and attorney general. In much of California today, even obviously ill patients with a doctor's recommendation are routinely arrested, a policy set by the previous administration.

At least one medical-marijuana organization -- Californians for Compassionate Use/Lake County Cannabis Farm -- has opposed this plan, for several reasons including that it would require a recommendation from a California (not out-of-state) physician in order to issue a card, would require the state health department to specify a maximum amount of marijuana that could be grown or possessed, and would require annual re-application and fees. But supporters see the plan as a remarkable product of consensus and cooperation between law enforcement (which wants a "bright line" between medical and recreational use) and patients (who want freedom from arrest and prosecution).

The task-force recommendations would allow registered patients to work together collectively to grow marijuana, but would not allow a county to designate an organization which distributes medical marijuana to administer the registration-card system. Besides the patient and doctor, a caregiver role is also recognized because many of the patients are too ill to grow their own marijuana, and no one will be allowed to sell it to them.

The Task Force plan is expected to become SB 848, which is set for a committee hearing in the legislature on July 13.


Comment

This proposal was made public only recently, and we saw it as we went to press, so we have not been able to research it further, and do not know the positions of the various medical-marijuana organizations or advocates. Ordinarily we would have delayed this report for our next issue, but that would be too late to inform our readers before the scheduled hearing date of July 13.

This proposal could change for better or for worse, or be killed entirely, in the legislative process. It is important that those most affected -- patients who may need medical marijuana -- be involved.



Africa, Access, and Patents: Moving Fast

by John S. James


The U.S. government's use of its economic power to block almost all access to modern medicines in developing countries -- stopping those governments from licensing cheaper copies of patented pharmaceuticals even when allowed by international treaties, just to maintain the sanctity of pharmaceutical patents, even when the drugs are not marketed in those countries anyway so no profit would be lost -- has moved into public awareness with amazing speed. Key events have been recent high-profile demonstrations at Vice President Gore's presidential campaign appearances, release of a State Department document detailing Gore's role in U.S. policy, and a Geneva, Switzerland meeting March 25-27, 1999, on compulsory licensing (see AIDS Treatment News #317 on the State Department document, and #314 and #317 on the Geneva meeting). Due largely to the demonstrations against Gore, this issue is now being discussed by members of Congress and researched by journalists around the world.

The key fact in the development of this issue is that people are beginning to talk to each other. There is still a long way to go. What is not widely known is that in the U.S., this matter was almost totally absent from public and official awareness as recently as four months ago.

[Five years ago, when the GATT global trade treaty covered pharmaceutical patents for the first time -- creating a 10-year timetable for developing countries everywhere to install U.S./European style pharmaceutical patents -- we realized that a train wreck had been scheduled, as the changes required would kill millions of people if implemented as intended; in HIV, all scientifically proven treatments are patented, and prices are usually set at rich-country levels even in the poorest regions, completely prohibiting access. Similar problems can be expected in other diseases where medical progress is rapid enough that new drugs offer major advantages. But for four years we could not find anyone who knew enough about the problem to get us started in researching it. That changed last August, with a visit from Bob Lederer and John Riley of ACT UP/New York, who came to interest us, not knowing we were already interested; inspired by New York AIDS doctor Alan Berkman, they were helping organize the group which later became the Health GAP Coalition. They referred us to the Web site of the Consumer Project on Technology, http://www.cptech.org , where we found the technical background needed for our first article, "GATT and the Gap: How to Save Lives," AIDS Treatment News #307, November 20, 1998.]

Small signs show the depth of the change. A month ago, an email list of organizers started by the Health GAP Coalition quickly grew to over 100. Yesterday, to help a friend get up to speed on the issue, we forwarded two days worth of emails -- more than 15 on this subject important enough to forward, not including some of the major email lists which we receive at a different address. While forwarding those messages, two more arrived that needed to be sent as well -- and these did not yet include any reports from the Philadelphia demonstration at Gore's campaign stop on that day (June 28; 400 people showed up on five days' notice, according to ACT Up/Philadelphia). A year ago, we had never received a single email, phone call, or letter on this subject.

Here are two statements to give our readers a sense of the issue -- one regarding compassion, the other providing technical background.


Statement of Sean Strub, Founder of POZ Magazine

The following is from a talk by Sean Strub at the National Association of People with AIDS awards luncheon, hosted by Congresswoman Donna Christian-Christiansen, June 21, 1999:


On behalf of POZ Magazine, POZ en Espanol, and our staff, interns and readers, I thank NAPWA for this award.

Part of the reason we are here today is to launch National HIV Testing Day, which is next Sunday, in the hopes that it will help encourage people to become aware of their HIV status.

But for those of us most intimately involved in AIDS activism -- and AIDS policy -- there is another test facing us. A test of humanity, compassion and justice.

The eminent Doug Ireland wrote it succinctly in his Public Eye column in the most recent POZ, which focused on AIDS in Africa:

The Clinton-Gore "international AIDS policy is politically smart-bombing Third World countries to save profits, not people with AIDS. The administration, in cahoots with the pharmaceutical industry, is using economic pressure and political blackmail to stop developing countries from making inexpensive copies of patented AIDS drugs."

The architect of this tragic campaign is our own Vice President Al Gore, a man who professes great compassion in public but is in fact promoting murderous policies in private.

This is sadly familiar -- one more person who raised the hopes of PWAs by vowing that he would do better, be more sincere, work harder to save lives but who has turned out to be, at best, I pray, only temporarily misguided.

According to Gore and other proponents of the administration's policy, it is a simple question of protecting the profits of drug companies so their financial incentive to invest further in research isn't "compromised."

I haven't yet heard them address the needs of the hundreds of thousands of people with AIDS -- mostly Africans -- who are being profoundly compromised by grueling AIDS deaths of the kind we, fortunately, see less often here in the states these days.

But because we see them less often in this protease era, doesn't mean we should forget what it was like to watch loved ones wither and die before our eyes. Die in pain. Emaciated. Hollow-cheeked. Without control of one's bodily functions. In shame and agony.

Those deaths are horrible memories for most of us, but daily realities for people in Africa. When I was at the Matabele AIDS Clinic in Bulawayo, Zimbabwe, last December I met people with AIDS who were determined to make sure they died on a Monday or Tuesday. Why? Because Wednesday was funeral day in Zimbabwe. Stay-aways from work are scheduled for Wednesdays; families plan on getting together on Wednesdays; funerals are bunched together to save money. On Wednesdays. For people who died on a Thursday or Friday or Saturday, it was more difficult -- and costly -- for their families to preserve the body for a Wednesday funeral.

Profits vs. people. An old battle. But the truth -- and the potential solution -- is more complicated. I am alive today because of a profit-driven pharmaceutical research system. I know that.

But I also know that if South Africa were to produce generic drugs -- and didn't pay a penny in royalty to the developers of those drugs, which is NOT their proposal by the way -- the profits of Roche, Glaxo, Bristol Myers Squibb and the others would not suffer one bit. The cost of drugs -- especially new drugs -- bears virtually no relationship to the actual cost of manufacturing those drugs. Other costs -- including overhead, research and marketing (including advertising in POZ) and profit margins that are the envy of the Fortune 500 -- all of this helps drive the costs to as high as the market will bear in the developed world. As high as the market will bear. The market for survival.

We need a different model in the less developed world, one which is based on a very different economic and political reality than that which we find in the US...


South Africa: Open Letter to Vice President Gore

Over 250 people, mostly health experts and leaders of AIDS organizations, signed the following letter to U.S. Vice President Gore; 16 of them are from South Africa. The deadline for signatures was June 30.


Dear Vice President Gore:

We are writing to express opposition to trade pressures you are bringing against the people of South Africa over their struggle to obtain access to essential medicines.

The White House dispute with South Africa concerns three basic points.

  1. The South Africa government has indicated it wants to use compulsory licensing of medical patents to produce cheaper copies of HIV drugs and other essential medicines. This is of course legal under the WTO/TRIPS agreement, subject to Article 31 safeguards.

  2. The South Africa government wants to authorize "parallel imports" of pharmaceuticals, so that it can buy drugs in the United States, Europe or elsewhere, in order to get the best world price. As you know, parallel importing of pharmaceuticals is legal under Article 6 of the WTO/TRIPS agreement, and is a common practice in Europe.

  3. The South African government has approved generic versions of Taxol, a U.S. government invention for treating cancer.

As co-chairman of the U.S./South Africa Binational Commission (BNC) you have authorized a wide range of trade pressures against South Africa, much of which is documented in a February 5, 1999 report to the Congress by the U.S. Department of State.

Despite increasing criticism of the U.S. bilateral pressures on South Africa, here and internationally, your office has authorized new trade pressures against South Africa on April 30, 1999.

The April 30, 1999 announcement of a Special 301 out-of-cycle review of trade pressures against South Africa ignored every shred of information that has been provided to your office by public health groups. Indeed, this most recent announcement is basically a recycled version of the February 16, 1999 submissions by the Pharmaceutical Research and Manufactures Association (PhRMA), the trade association that represents giant drug companies like Bristol-Myers Squibb, Glaxo, Pfizer, and Johnson and Johnson that are trying to stop South Africa from implementing policies to cut costs for pharmaceuticals in South Africa.

It is shocking that the U.S. government is adapting such an aggressive trade policy on behalf of U.S. pharmaceutical companies, when all of sub-Saharan Africa is confronted with a public health crisis of historical dimensions. The U.S. Surgeon General, Dr. David Satcher, recently wrote in the Journal of the America Medical Association that "HIV/AIDS can be likened to the plague that decimated the population of Europe in the 14th century." Dr. Satcher says that "in many southern African countries, HIV/AIDS has become an unprecedented emergency, with 20% to 26% of people between the ages of 15 and 49 infected." This is a here-and-now emergency. It is not a hypothetical or potential emergency. These people will die without access to pharmaceutical drugs.

Your response to this emergency should be to find ways to save lives. But look what you are doing:

  • You are aggressively seeking the repeal of legislation in South Africa that would permit that country to do what nations in Europe do, use parallel imports to buy drugs at the best world price. South Africa wants to use market forces to cut drug costs. You are pushing to protect pharmaceutical companies from global competition, thereby forcing the South Africa people to pay premiums to buy drugs.

  • You are punishing South Africa for even speaking out in favor of compulsory licensing of HIV/AIDS and other essential medicines. The April 30, 1999 report on South Africa complains that:

    During the past year, South African representatives have led a faction of nations in the World Health Organization (WHO) in calling for a reduction in the level of protection provided for pharmaceuticals in TRIPS.

    In fact, everything South Africa is seeking to do is legal under the WTO/TRIPS agreement, so this and countless other statements by U.S. government officials are bald lies. But regardless, the exercise of free speech in international forums is an astonishing basis for trade sanctions. As an elected official, indeed, as a human, how would you act if 20 percent of all sexually active young people in the United States were infected with a fatal disease, and a foreign country was trying to prevent you from purchasing drugs on the global market to save money, and was preventing you from licensing firms to manufacture life saving medicines? Would you simply show up at the World Health Assembly and docilely applaud the actions of that country? Even if that foreign country was engaged in a relentless public relations campaign to label every legal action as a form of piracy or lawlessness? At what point would you have the guts to tell the world the truth, and to speak out on behalf of millions of infected young men and women?

  • You are punishing South Africa for giving approval to generic versions of Taxol, a cancer drug that was invented by the U.S. government. There are aspects of the U.S. government complaint about Taxol that are absurd, on technical grounds, such as the insistence that South Africa extend longer periods of data exclusivity than are required in the United States. But the larger issue is more basic.

Why on earth should Vice President Al Gore or any other U.S. government employee seek to prevent global competition for Taxol, a life saving cancer drug that was invented and developed by the U.S. National Institutes of Health? Taxol was in NIH sponsored Phase III trials before the Bush Administration gave BMS [Bristol-Myers Squibb] exclusive rights to use NIH research for drug approvals. What is the moral basis for extending the BMS monopoly on Taxol in a country that is so poor?

As the Vice President of the United States you are in a position to do much good or much harm in the world. U.S. voters will soon be asked to determine if you should be the next President of the United States. Please explain why they should choose you.

Sincerely,

*****

Note: As this issue goes to press, there are signs of potential movement in U.S. policy -- although the outcome remains unclear.


For More Information

To help the effort to change government and industry policies on these issues, or for more information, contact the Health GAP Coalition, c/o AIDS Treatment & Data Network, 800-734-7104, or richard@atdn.org. The Health GAP Coalition has a Web site at http://www.healthgap.org



ISSN # 1052-4207

Copyright 1999 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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