AIDS Trestment News
September 4, 1998

Post-Exposure Prevention (PEP); What to Do If the Condom Breaks?

When healthcare workers have serious exposure to HIV (through a needlestick, for example), they are likely to be started on a two- or three-drug regimen within hours (within two hours if possible), and continue taking the drugs for four weeks. The U.S. Centers for Disease Control and Prevention (CDC) has published guidelines recommending this preventive care, since observational studies had suggested (although not proved) that use of AZT alone reduced the risk of HIV infection by about four fifths.

Treatment must start as soon as possible after the incident. Many experts believe that after 72 hours it is too late, since the virus will already be integrated into human cells. In practice it is difficult to get into treatment within 72 hours after an accidental exposure -- especially if those exposed, and friends or associates they turn to for advice, do not know ahead of time that such treatment is available, and do not know how to contact a program or doctor who can provide it.

Fortunately this preventive treatment lasts only for four weeks and then the drugs are stopped. Therefore it does not involve a commitment to long-term antiretroviral use. The PEP programs include counseling to help people reduce the risk of further exposures.

In San Francisco alone, it is estimated that 600 to 800 people become HIV-positive each year. Hopefully, post-exposure prevention can be one part of the efforts to prevent these infections.

In or Near San Francisco

In the San Francisco area (if you live close enough that you can come in for repeated visits), you can join a local research program for non-occupational exposure; it pays for the drugs, tests, and other expenses, and provides counseling and certain other services as needed. You will be encouraged to give your real name, but if that is a problem, the staff will accept whatever name you give. There is no placebo, and you can stay in this program to benefit from the testing, etc., even if you choose not to take the drugs. The drugs are used for four weeks, and then there are occasional visits for followup blood tests. The entire program lasts one year, and includes nine visits to the research clinic.

If you live in or near San Francisco and have been accidentally exposed to HIV, call the research program hotline number, 415-514-4PEP, 24 hours a day (the previous number, 415-502-5PEP, will also work; the new one may be easier to remember). You may need to leave a phone number for a return call, which you will probably receive within half an hour. Or you can drop in at the PEP site, during certain hours, at either of two locations: San Francisco General Hospital Ward 4C, or the City Clinic on 7th Street between Harrison and Folsom. No appointment is needed, but call the number above to check when the clinics are open. Do not wait for open hours; use the telephone hotline so that if you are found to need treatment, it can be started immediately.

Other Locations

If exposed to HIV, you need to locate either a PEP program, or a PEP-knowledgeable physician. Unfortunately there is no national list of programs. A local AIDS service organization may be able to help; you can find one in your area by calling the National AIDS Hotline, 800-342-AIDS, 24 hours a day. (For a Spanish-speaking operator, call 800-344-SIDA, 8 a.m. to 2 a.m. Eastern time; for TTY, call 800-243-7889, 10 a.m. to 10 p.m. Monday through Friday Eastern time.)

Who Is Likely to Need Treatment?

Here are some of the guidelines used by the PEP program in San Francisco to decide who may benefit from drug treatment. Other PEP programs, or private physicians experienced with PEP, are likely to use similar criteria.

There must be a "significant" sexual or injection drug use exposure. "A significant sexual exposure is when a person has receptive or penetrative anal intercourse, receptive or penetrative vaginal intercourse or receptive oral intercourse with ejaculation. Significant sexual exposures are always without a condom (or when the condom breaks) and with someone who is HIV infected. Since it is not always possible to know if the person you are having sex with is HIV infected, PEP should be offered to anyone who has had a significant sexual exposure with a 'high risk' partner. High risk partners are men who have had sex with men, anyone with a history of injection drug use, sex workers, and anonymous partners." (Quoted from Twenty Top Questions and Answers About PEP; to obtain this document, see "For More Information," below.)

What Treatment Is Used?

Most people are treated with AZT plus 3TC for four weeks. The drugs are combined into a single tablet (called Combivir™); the adult dose is one tablet, taken twice a day.

The San Francisco program also offers an alternative of ddI and d4T, for those who do not want to take AZT, or when the alternative is indicated by the partner's treatment history.

If it is suspected from clinical history that the patient's partner may have drug-resistant HIV, then a third antiretroviral may be added -- the protease inhibitor nelfinavir.

Besides the antiretrovirals, the program includes counseling on risk reduction, testing for sexually-transmitted diseases and treatment if necessary, hepatitis B and C screening and hepatitis B vaccination or referral, and pregnancy testing. (Pregnant women are allowed to enter the program and use the antiretroviral drugs.)

What Has Been Learned So Far?

At this time about 150 people have been treated; no one has become HIV positive. Since the risk from a single exposure is fairly small, this could have happened by chance.

There has been no serious toxicity of the medications, and over 80% of the volunteers have completed the full four weeks of treatment.

One of the concerns of the program -- that people would take more risks because of it -- is too early to evaluate with the short follow-up so far.

For More Information

Several documents about post-exposure prevention, and the San Francisco program in particular, are available on the Web. The most important are:

• "Twenty Top Questions and Answers about PEP." At http://hivinsite.ucsf.edu/topics, select "Post Exposure Prevention" in the list of topics, then select "PEP: The San Francisco Feasibility Study," then select "Top Twenty Questions..." Many other documents about PEP, and the San Francisco study of non-occupational exposure, are also available on this site.

• "What Is Post-Exposure Prevention (PEP)?" Select this article at http://hivinsite.ucsf.edu/prevention/fact_sheets.

• "San Francisco PEP Update: What Happens," by Bill Snow and Larry Hanbrook, ACT UP/Golden Gate Writers' Pool, published in Bay Area Reporter, April 2, 1998. Go to http://www.actupgg.org, select "Writers' Pool articles," select "1998," then select the article, in the list which is sorted by date. (Note: The organization of this site, and the other sites also, may change in the future.)

• Background on PEP for occupational exposure to HIV and other blood-borne illnesses can be found at http://epi-center.ucsf.edu.

• The government guidelines for occupational exposure (Public Health Service Guidelines for the Management of Health-Care Worker Exposures to HIV and Recommendations for Postexposure Prophylaxsis) can be found at many Web sites; the document has been translated into convenient Web format (to avoid a separate download step) at http://www.healthcg.com/hiv (select "Guidelines"). As of this writing, the current version was published May 15, 1998.

New Drug Pricing Consensus Letter, Sign-Ons Requested

Treatment activists are circulating a letter on new-drug pricing -- especially regarding abacavir (Ziagen™) and efavirenz (Sustiva™), which are likely to be approved soon. This consensus statement, to be signed by organizations and individuals, addresses concerns that the new drugs may be priced significantly higher than others in the same class (nucleoside analogs, and non-nucleoside reverse transcriptase inhibitors, respectively).

The statement notes:

• The longer survival of patients today allows manufacturers to charge lower prices and still have a healthy profit and incentive for further research;

• Abacavir and efavirenz will be used by both treatment naive and treatment experienced patients, making the potential market very large;

• Both the development and production costs of these drugs appear to be much lower than for the protease inhibitors;

• Because patients are using more drugs today, the overall decrease in the cost of HIV therapy could be reversed if prices are set too high;

• State ADAP drug-assistance programs often face bankruptcy before the end of their fiscal year and must stop providing vital drugs; both ADAP and Medicaid programs are under close scrutiny to cut costs; and HMOs are also starting to restrict drugs because of the expense.

• Exploitative pricing will trigger widespread hostility, contentious debate, and closer scrutiny of industry practices in general.

This consensus letter is sponsored by the Fair Price Working Group, which currently includes Martin Delaney of Project Inform, Bill Bahlman of ACT UP/New York, Ron Baker of San Francisco AIDS Foundation, Dave Gilden of GMHC Treatment Issues, Linda Grinberg of the Foundation for AIDS and Immune Research, and John S. James of AIDS Treatment News. To obtain the full statement, or to sign for your organization or as an individual, contact Linda Grinberg by email at linda_grinberg@prodigy.com, by fax at 310-471-4565, or by voicemail at 310-471-4108.

Hepatitis C: New Treatment Overview

by Jeffery Stoia

Hepatitis C -- called the silent epidemic -- affects 4 million Americans and as many as 40% of persons with HIV disease. It is the number one reason for liver transplants in the U.S. Only one out of four people with the disease know they have it.

Until June of this year, only one drug, ineffective and expensive, had been approved by the FDA to treat hepatitis C (HCV). That was alpha interferon. At best it was said to produce a long-term remission rate of 5% in relapsed hepatitis C patients. Side effects included fatigue, joint pains, fever, anxiety, and severe depression. According to the HCV Global Foundation, interferon was considered for people with HCV and HIV co-infection only if their HIV was well controlled.

On June 3, 1998 the picture changed when the FDA approved a second therapy. This was Schering-Plough Corporation's REBETRON™, which combines in a single "bundled" package alpha interferon for injection, and oral doses of ribavirin.

Ribavirin, a synthetic nucleoside, has been approved throughout the world as a broad-spectrum antiviral but has been stalled in the U.S. because of questions concerning its potential usefulness in treating HIV. Its chief side effect is anemia. (Ribavirin is now also called REBETOL®, which is a brand name of Schering-Plough, which recently acquired worldwide rights to the drug from its developer, ICN Pharmaceuticals.)

In approving the new combination therapy, the FDA labeled it as indicated only for patients who had "relapsed" following interferon alone. (This may change soon; Schering-Plough has submitted a supplemental new drug application to the FDA for the treatment of naive patients, and the new application is currently under priority review.) For relapsed patients, the cure rate climbed sharply with the combination ("cure" defined as undetectable HCV virus, even after therapy has ended). In two major clinical studies, patients given interferon plus placebo had a cure rate of 5%, while those given interferon plus ribavirin achieved a rate of 46%. The usual length of the two-drug treatment is six months.

Meanwhile, Schering-Plough, which markets the bundled drugs, was sharply criticized from several quarters. Some saw Amgen's brand of interferon as more effective than Schering's, but hard to prescribe because of the way the two drugs were packaged and sold together. Some pointed to the unfair monopolistic advantage Schering-Plough had received with the FDA decision. Others objected to patient restrictions and to drug "bundling" in a single package which sells for as much as $1440 a month, nearly double the cost of interferon treatment alone. One protester wrote, "This is as absurd as the notion that aspirin would need separate approvals when used in conjunction with each possible kind of antibiotic on the market."

Robert Consalvo, on behalf of the drug company, pointed out that in controlled clinical studies, the combination of INTRON® A (Schering-Plough's alpha interferon) and ribavirin demonstrated a significant improvement over standard monotherapy -- and that Schering is supplying the product free to many research volunteers. "Both alpha interferon and ribavirin have known side effects," he added, "but no synergistic toxicity was seen in clinical studies with REBETRON."

HCV is a blood-borne virus. Testing is all-important, and patients usually need to take the initiative to be tested. The virus tends to progress slowly and insidiously over 20 to 30 years, so that until they reach an advanced, chronic stage, as many as 75% of infected people are totally asymptomatic. People at risk of acquiring HCV include drug users, hemodialysis patients, those with tattoos, those with multiple sex partners, and anyone who had a blood transfusion before 1990. Some people may contract the virus through unprotected sex. People with HIV and other immunodeficiencies are considered a major risk group.

AmFAR (the American Foundation for AIDS Research) is conducting the first study of ribavirin plus alpha interferon for treating hepatitis C in persons who also have HIV. Two hundred volunteers will be enrolled in 14 U.S. cities. (For more information about this study, see AIDS Treatment News #295, May 15, 1998.)

[Jeffery Stoia is a medical writer and editor who also volunteers for AIDS service organizations in San Francisco.]

For More Information

• At this time the most current and in-depth medical information on the use of the newly approved combination treatment is the transcript of the discussion of the FDA's Antiviral Drugs Advisory Committee meeting of May 4, 1998. This transcript, about 90 pages single spaced, is available on the FDA's Web site, http://www.fda.gov. Select "Dockets," then "FDA Advisory Committees Menu," then "Center for Drug Evaluation and Research (CDER)," then "Antiviral Drugs Advisory Committee ." The hearings are listed by date, and can be downloaded in either pdf or rtf file format. (The rtf -- rich text format -- is much more compact and downloads faster, but you may need to turn off automatic line numbers in your word processor, to prevent overprinting.)

• A major article on the controversy about the bundling of the two drugs -- forcing patients to pay for Schering-Plough's interferon in order to buy ribavirin in the U.S. -- is scheduled to be published in the San Francisco Bay Times, September 3, 1998. You can obtain a copy by sending a self-addressed stamped envelope to: San Francisco Bay Times, 525 Bryant St., San Francisco, 94107; request the hepatitis C article by Bruce Mirken.

• A number of articles are on the Web site of The American Liver Foundation, http://sadieo.ucsf.edu/alf/alffinal.

  
  

HIV and Hepatitis Physician Education

San Francisco Sept. 12

"HIV & Hepatitis: Complexities of Co-infection," a continuing medical education program primarily for physicians, will be presented Saturday September 12 from 8:30 a.m. to 12:30 p.m., at the California Pacific Medical Center Davies Campus (auditorium, level B). There is no charge to attend, but advance registration is requested.

The learning objectives are: "Describe the prevalence of co-infection with HIV and hepatitis; Describe the natural history of co-infection with HIV and hepatitis; Describe currently available data on treatment options for hepatitis B and C; Describe the impact of co-existing hepatitis on response to highly active antiretroviral therapy."

This program, which includes four lectures and a panel discussion, is presented by the Community Consortium and the California Pacific Medical Center, with unrestricted educational grants from Glaxo Wellcome Company and Roche Laboratories, Inc. To register, or for more information, contact the Community Consortium, fax 415-476-6948, phone 415-502-0657.

IHV 1998 Annual Meeting ("Gallo Lab Meeting")

Program, Many Talks on Web

Many of the world's leading researchers in the virology and immunology of HIV disease present new information at the annual meeting of the Institute for Human Virology; the 1998 meeting occurred August 23-29 in Baltimore. The complete list of speakers and their topics -- about 200 scientific presentations -- is available at http://www.ihv.org. About 1,000 people attended.

Many of the talks will be available through audio and slides at http://www.helix.com, an educational site for health care professionals developed by Glaxo Wellcome; there will be a link from the IHV site. Unfortunately some presentations could not be included, because researchers are concerned that certain medical journals will not publish new data if it is released first on the Web.

Abstracts of the talks are not on the Web, but will be published in the next Journal of Human Virology, which should be available in late September.

Fomivirsen Approved for CMV Retinitis: First Antisense Drug

On August 27 the U.S. Food and Drug Administration approved the first drug using antisense technology -- fomivirsen (Vitravene™) for patients "who are intolerant of or have a contraindication to other treatments for CMV retinitis or who were insufficiently responsive to previous treatments for CMV retinitis." This drug is injected directly into the eye, and is given monthly, except that the first two doses are two weeks apart. The drug was developed by Isis Pharmaceuticals, in cooperation with CIBA Vision, a unit of Novartis AG.

Antisense drugs work by blocking a specific gene from producing the protein it codes for. This kind of drug has great potential importance because it can be targeted against only a single gene -- either in a virus or other disease-causing organism, or an abnormal human gene. This highly specific action should improve efficacy and reduce side effects. The development of antisense drugs has been slower than some had expected, however, because of technological difficulties such as designing compounds which can readily enter cells.

Fomivirsen was considered on July 22 by an FDA advisory committee (the Ophthalmic Drugs Subcommittee of the Dermatologic and Ophthalmic Drugs Advisory Committee). The subcommittee voted 5-2 for approval, with all the clinicians voting to approve the drug; but there was much concern about the small number of patients in the trials, especially the pivotal study for "first line" use, which compared 18 patients randomly assigned to immediate treatment vs. 10 assigned to deferred treatment. The reason for these small numbers is that the availability of protease inhibitors greatly reduced the incidence of new CMV retinitis, making it very difficult to enroll volunteers into the trial. This small number of patients is probably the reason that the FDA did not grant the additional "first line" approval (for patients previously untreated for CMV retinitis) that the company had requested. There were more volunteers in the studies of fomivirsen for patients who had failed previous treatment for CMV retinitis.

An application to market fomivirsen in Europe is currently being reviewed.

Some information is available at http://www.fomivirsen.com and at http://www.cibavision.com. Also, the transcript of the FDA advisory committee hearing (on 7/22/98) will probably be placed on http://www.fda.gov, but it is not there as this article goes to press.

Prison Issues: National Conference, Web Sites

A major national conference on prison issues (medical and other), including over 150 workshops on varied topics, will take place September 25-27 at the University of California at Berkeley. "Critical Resistance: Beyond the Prison Industrial Complex," is sponsored by many prison, academic, and legal organizations, including California Coalition for Women Prisoners, California Prison Focus, and the Prison Activist Resource Center.

Major topics include prison as industry, law and policy, research and activism, alternatives for addressing problems such as drugs and homelessness, human rights and conditions of confinement, education in prison and otherwise, and media representations & popular culture. HIV and healthcare workshops include disabled prisoners, women's health, medical neglect in prison, alternatives to incarceration for the disabled, terminally ill and elderly, responding to the infectious disease epidemic within the prison industrial complex, and health and human rights in prison. For more information, contact Critical Resistance, P.O. Box 339, Berkeley, CA 94701, 510-643-2094, email critresist@aol.com, Web http://www.prisonactivist.org/critical/index.html.

Prison-related Web sites include:

• http://www.prisonactivist.org, Prison Activist Resource Center, includes prison issues, prison news, a current list of over 150 prison issues and reform organizations, and almost 50 prison-related Web links.

• http://www.igc.org/justice, JusticeWeb, includes about 180 articles on medical care in prisons, and about 50 on HIV, as of our search on September 1. Click "Search," then enter 'HIV', 'medical', or other keyword you are searching for (without the single quotes), and click "Search."

• http://www.wco.com/~aerick/link.htm#hlt, Prison Law Links, includes over 200 Web links on: Health and Well-Being, Prison Information and Resources, Activism, Corrections, Correctional Officers, Education, International, Journals and Magazines, Law and Prisons, and poetry, art, and other prison-related sites.

[California note: The Caravan for Prisoners' Human Rights, a protest by many organizations on October 17, will carpool from San Francisco and other cities to Chowchilla women's prison for a noon rally, and then from there to Corcoran prison for a 2:30 p.m. rally. Major focus will include substandard medical care, worsening conditions for California prisoners, and denial of access to news media. For carpool and other information, call the HIV in Prison Committee of California Prison Focus, 510-533-2590.]

Help Wanted: Executive Director, Project Inform

Project Inform, the largest U.S. AIDS treatment information and advocacy organization, is seeking an executive director. This position will be available on January 1, 1999, and is located in San Francisco. The current executive director, Annette Brands, is leaving on February 28, 1999.

Qualifications are "three to five years of successful management experience in either the not-for-profit or for-profit environment. Excellent personnel management/people skills, organizational management, fund development, and leadership skills. Demonstrated success in program development and public relations. Effective team building and innovative management skills. Possess exceptional communication skills and external relations capabilities. Previous experience working effectively with a board of directors.

"Knowledge of HIV/AIDS issues and experience either personally, professionally, or through volunteer activities. A commitment to the mission of Project Inform and to fight to end the AIDS epidemic."

For more information, obtain the four-page Executive Search Announcement from www.projinf.org.

ISSN # 1052-4207

Copyright 1998 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.