Lamivudine (3TC) Approved 
for Combination Use with AZT

The Package Insert

The "package insert" for 3TC -- the document which defines what the FDA will allow the company to say about the drug when marketing it to doctors, and which will be published in the PHYSICIAN'S DESK REFERENCE (probably appearing in the Supplement early next year) -- summarizes the information which the FDA used in granting the approval.

• In laboratory studies, 3TC has been shown to be synergistic with AZT, meaning that the combination works better than would be expected from how well the two drugs work separately.
  
  
• In patients, when 3TC is given alone, resistant virus emerges rapidly, usually within 12 weeks. Resistance to 3TC is believed to be caused by a mutation at position 184 in the gene which codes for the viral enzyme reverse transcriptase. In some patients who had AZT-resistant virus when they started 3TC, sensitivity to AZT was restored after 12 weeks of 3TC treatment.
  
• Combining 3TC with AZT delayed the emergence of 3TC-resistant virus. [Note: As the three items above suggest, it is difficult for HIV to be resistant to both AZT and 3TC at the same time. But it is not impossible; the package insert points out that strains simultaneously resistant to both drugs have been found.]
  
  
• 3TC may be taken with or without food. (When taken with food, absorption is slower; the maximum blood levels are less, but apparently longer lasting, than if the drug is taken while fasting. The total systemic exposure to the drug -- the "AUC", or area under the curve -- is about the same in either case.)
  
  
• 3TC is mostly eliminated unchanged in the urine. In persons with kidney impairment, the dose needs to be decreased because elimination is slower; specific instructions are given in the package insert.
  
  
• A five-day study found that in persons using double- strength TMP/SMX (Bactrim, or Septra) once a day in combination with 3TC, the total blood level of 3TC (the AUC) was increased about 44%. The effect of higher doses of TMP/SMX has not been studied. [This suggests that the dose of 3TC might be reduced for persons using Bactrim or Septra; however, the package insert does not include instructions for doing so.]
  
  
• There is no information in the package insert about interaction of 3TC with other drugs (besides AZT and TMP/SMX) which persons with HIV may be using. And there are no studies of such interactions going on now.
  
  
• No studies have been done to see if the pharmacokinetics (absorption, elimination, etc.) of 3TC vary between races or between sexes, or are different in persons age 65 or older.
  
  
• The recommended dose of 3TC for adults and adolescents (12- 16 years) with average body weight is 150 mg twice daily, in combination with AZT. For adults weighing less than 50 kg (110 lbs), the recommended dose is 2 mg/kg twice daily. For infants and children, different doses and precautions are recommended. The drug is supplied in 150 mg tablets, and also in a strawberry/banana flavored solution for oral administration, containing 10 mg of 3TC per ml.
  
• Animal studies found no evidence of birth defects even at doses far higher than the human dose; however, there was "some evidence of early embryolethality" in rabbits at the human adult dose and higher, but none in rats at up to 130 times the human dose. 3TC "should be used during pregnancy only if the potential benefits outweigh the risks." Since there are no adequate studies of 3TC in pregnant women, an Antiretroviral Pregnancy Registry has been established, and physicians are encouraged to register pregnant patients, so that in case there are any problems with this drug in pregnancy, they can be identified as early as possible.
  
  
• Mothers should discontinue nursing if they are using 3TC.

Adult Studies

There have been four controlled studies of 3TC in combination with AZT in adults. Two of these studies were for persons who had used little or no AZT, and two were for persons who had used AZT extensively. A total of 974 HIV-positive volunteers were enrolled in these studies (not all of them received 3TC). In those who had not used AZT before, the average CD4 increase was about 50. Those who had used AZT had an increase of about 30. These increases were sustained for longer than 24 weeks. [These figures are from a summary published in an FDA Talk Paper on November 7. The full data are more complex, because of differences between the maximum average CD4 cell rise, and the average at week 24, week 52, or other specific times.]

The average decrease in viral load was about 0.9 logs (7.9- fold) in AZT-naive volunteers, and about 0.7 logs (5-fold) in those who were AZT-experienced, when the doses of 3TC and AZT were the same as those now recommended. However, there was much variation from patient to patient; the standard deviation of the decrease was 0.8 logs in each case.

Pediatric Use

The package insert contains the following warning:

"Pancreatitis in pediatric patients: In pediatric patients with a history of pancreatitis or other significant risk factors for the development of pancreatitis, the combination of Epivir(TM) and Retrovir(R) (zidovudine) should be used with extreme caution and only if there is no satisfactory alternative therapy. Treatment with Epivir should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur (see Adverse Reactions)."

In two small trials, one studying 3TC alone and one studying it in combination, about 15 percent of pediatric patients developed pancreatitis. No one knows why the risk was so much higher for them than for adults (in whom pancreatitis was observed in only three of 656 volunteers in controlled clinical trials, less than 0.5%); this may have happened because the children were much sicker than the adults when they started treatment.

At the meeting of the Antiviral Drugs Advisory Committee, data were presented showing that there were generally predisposing factors in the infants and children who developed pancreatitis; however, little of this data was included in the package insert. (The package insert did note that high amylase levels, a danger sign for pancreatitis, occurred in 23% of pediatric patients with abnormal baseline amylase values, vs. only 3% for those with normal baselines.) A major pediatric study is now ongoing, so there will be more data eventually on the risks and benefits of pediatric use. Unfortunately this trial is still recruiting, and it is likely to remain blinded for two years after the last patient is enrolled, meaning that there may be no data available for well over two years.

Comment -- Other Issues

Some areas of concern -- and also praise for Glaxo-Wellcome's commitment to testing pediatric use of 3TC more thoroughly than the law requires -- came out at the Antiviral Drugs Advisory Committee meeting but were not explained in the package insert.

Cross Resistance

A theoretical risk in using 3TC, in adults as well as children, is that laboratory studies suggest that it might cause virus to rapidly become resistant to ddI and ddC, as well as to 3TC. This concern arose because most patients who use 3TC (even with AZT) develop a mutation at position 184 of the reverse transcriptase gene which gives the virus high-level resistance to 3TC -- and in laboratory tests, the same mutation developed when viruses were exposed to ddI, and it conferred low-level resistance to ddI. No one knows if this is important in practice, however -- especially because patients who become resistant to ddI after treatment with that drug seldom develop the mutation at position 184, but develop other mutations instead.

The concern is that patients might be able to start treatment with AZT plus ddI, or AZT plus ddC, and then benefit from switching to AZT plus 3TC when the first combination failed -- but that going the other way might not work, because the mutation which caused resistance to 3TC might also cause cross resistance to ddI or ddC. On the other hand, there may be no such problem at all. No one knows, because while many people who have previously used ddI or ddC have used 3TC, few have started with 3TC and then switched to ddI or ddC later; there do not even seem to be anecdotal reports.

Now that the combination of AZT plus 3TC has been approved -- including for first line use -- many people are likely to be starting therapy with it. Fortunately it would be easy to answer the question of whether this theoretical concern has any practical importance. All that would be needed is a small, rapid trial to see if persons who have used 3TC for some time do or do not still show an antiviral response to ddI. Since this trial would look for changes in viral load when ddI was started -- and viral load can change in days or weeks in response to an antiviral drug -- we could have the answer in a few months.

Glaxo has said that it will continue to address the question of cross resistance, and that it is looking at existing laboratory data in the U.S., and will look at data from clinical trials in Europe. Incidentally, there is even a theoretical possibility that the mutation at position 184 might be useful in some cases. Some researchers believe that it makes the reverse transcriptase enzyme work more accurately when it makes copies of the virus, thereby reducing the rate at which new mutations develop.

For some time it has been noted that when 3TC is used alone (which is not recommended), the viral load greatly declines, and then quickly comes back up again as resistance develops -- but usually it does not come all the way back to baseline, despite the fact that the virus then has high-level resistance to 3TC when that is the only antiviral the patient is using. No one knows why this happens; one theory is that the resistant virus cannot mutate as fast as the wild-type virus, and therefore the immune system can keep up with it better. If it turns out to be true that 3TC resistance slows HIV mutation, then it might make many kinds of antivirals work better, not only those targeted against the reverse transcriptase gene. As of today all this is only theory, however.

Controversy on Indications

There was controversy at the Antiviral Drugs Advisory Committee meeting about the recommendation to approve 3TC without restricting the indication to certain CD4 count ranges. A position paper by Michael Ravitch of the Treatment Action Group (TAG), dated November 6 and distributed that day at the hearing, supported the approval of 3TC, but also said that "the FDA should not allow Glaxo to promote the AZT/3TC combination among patients with over 300 CD4+ cells unless the company initiates studies with clinical endpoints in this population... Approval of the requested indication for 3TC would set a terrible precedent. If Glaxo wants an indication for the >300 CD4+ cells population, they should present a plan for a clinical endpoint study in that group."

TAG's major concern seemed to be that two large clinical trials showed no survival benefit from starting AZT early, compared to starting AZT later --even though the CD4 count seemed to show that those receiving the early treatment were doing better. Should AZT plus 3TC be approved regardless of T-cell range, when there may never be a trial to prove that it increases survival if started in early disease? Most activists argued against restricting the CD4 count range, however. For example, Project Inform's November 6 statement noted that the AZT plus 3TC combination had been found superior to AZT in every population tested, and that,

"While it might be ultimately desirable to see the drug tested in every imaginable subset of the HIV-infected population, there is no reason to require this prior to making the drug fully available and we believe it may even be unethical to do so. With the number of new drugs likely to become available over the next six to twelve months, it will simply be impossible to test for the clinical effects of each drug at each and every arbitrary stage of HIV disease."

Project Inform's statement also argued that restrictive indications would have little effect on the rich and well- insured, but would guarantee the continued dominance of AZT monotherapy in poorer populations, despite its obvious inferiority. It said that decisions about when to begin treatment (with any drug) should be guided by the consensus conferences periodically called for this purpose -- and that these conferences, not the sponsors' advertising, have been the principal determinants of drug use in the past. [The next consensus conference on HIV treatment is planned for early next year.]

Both Ravitch and Delaney spoke at the hearing, which included a public comment period. This writer also spoke; like Delaney, we urged the Committee not to restrict the CD4 range. We also said that standards for accelerated approval could be maintained primarily by the professional consensus of physicians and researchers; only when companies flout the professional consensus need the FDA step in to punish them (by restricting indications, or otherwise). That has not happened here, since many researchers and physicians believe that a clinical trial to prove superiority by clinical endpoints (mainly death and AIDS progression) is probably not feasible in early HIV disease.

[It would take a long time to obtain any endpoints from persons with early HIV disease -- and much longer to obtain enough endpoints for statistical proof. And if the two or more treatments being compared were approximately equal, it would probably be impossible to ever show superiority, which the proposed trials would be attempting to do; but if the treatment arms were significantly different, people would become aware of the difference, and the trial would have to keep many people on a treatment widely believed to be inferior,for a time long enough for many of them to suffer serious harm.]

Praise on Pediatric Testing

There has long been a major problem in getting drugs tested and approved for infants and children. About 80 percent of drugs now approved have no data to support special prescribing instructions for pediatric use, meaning that physicians often have to guess at what dose to use. (Infants and young children have differences in metabolism from adults, so adjusting the dose only for body size is often inadequate.)

To help make new drugs for serious and life-threatening conditions more available for children, the FDA finalized a new rule this year to allow a drug to be approved for children based on trials in adults, when there is pharmacokinetic and other information supporting pediatric use, and the drug and the disease are similar enough in adults and children to permit the adult data to be extrapolated. In developing 3TC, Glaxo-Wellcome went beyond what the new rule requires, and is conducting a major efficacy trial in children. It is fortunate that they have done pediatric studies -- which were not legally required -- because otherwise the pancreatitis problem would probably not be known to this day, and the drug would have been approved with no warning to physicians, which could have caused many preventable deaths.

Arthur Ammann, M.D., of the Pediatric AIDS Foundation, supported the accelerated approval of 3TC for pediatric use, and commended Glaxo-Wellcome for developing this drug almost simultaneously for children as for adults. He reviewed the pediatric data before the meeting, and noted the pancreatitis problem, but also noted the benefits of increased body weight, increased CD4, and decreased viral load in children -- despite the fact that they had more advanced disease when they began treatment than persons in adult trials.

"My final comments are a plea," Dr. Ammann concluded. "The early formulation of promising new drugs for serious and life-threatening diseases in children requires the performance of safety and pharmacokinetic studies from birth to adult life. They must become an industry standard. This company has set an example with 3TC. Tragically there will be a new class of drugs, protease inhibitors, which are likely o receive approval for adults without supporting data for use in infants. The urging of the pediatric community alone is insufficient to correct this inequity. As new drugs are reviewed for approval during all stages of development, questions must be asked by the Agency, and the Advisory Committees, as to why data for certain members of the HIV/AIDS community are lacking."

Expanded Access, Price, and Funding

About 35,000 people have received 3TC without charge in Glaxo Wellcome's expanded access program. (There were associated charges, however, such as for CD4 tests, which sometimes had to be paid by patients, as insurance companies were likely to reject payment on the grounds that the drug was experimental.) Now that 3TC is approved it will have to be paid for, although it will now be easier to get private or public insurance coverage for the cost. The price of 3TC to wholesalers is $3.11 per 150 mg tablet, making the annual cost of the drug $2,270 plus the wholesalers' and retailers' markups. This of course is in addition to the cost of the AZT.

For help with reimbursement, patients and physicians can call Glaxo Wellcome's reimbursement assistance line, 800/513-3028, from 8:30 a.m. to 7:00 p.m. Eastern time. There is a patient assistance program for persons with no other way to pay for the drug, but the company requests that one use the assistance line to check out other options first. Persons currently in the expanded access program have been about a one-month grace period to make arrangements to pay for the drug; the company has programs in place with the intention that no one will be dropped.

While traditional insurance has usually reimbursed for treatments which are FDA approved, managed-care plans often have formularies, lists of drugs which are regularly reimbursed. Not all FDA-approved drugs are included. Public-assistance programs are likely to have more severe limitations. The increasing number of expensive drugs, plus Congressional cuts in support for Medicaid and other programs, are rapidly leading to a crisis in drug reimbursement. Unless companies can restrain prices, and also improve the value of their products by providing better data on how to use them, their drugs will not be widely used in the future.

PMPA in Perspective

• Some people have tended to dismiss the finding that this drug can protect monkeys after exposure, since PMPA is chemically very close to PMEA, which is well known and already in clinical trials. We believe such quick judgment is a mistake. Even though the chemical change is small, PMPA is a new chemical entity. Even a small chemical change can have a huge impact on the safety, efficacy, and clinical potential of a new drug.
  
  
• PMPA, PMEA, another derivative of PMEA called bis-POM PMEA, as well as some other antivirals now being developed for human use, are members of a new class of drugs called nucleotide analogs (as opposed to nucleoside analogs such as AZT and ddI). Like nucleoside analogs, nucleotide analogs stop HIV replication by providing false building blocks which are incorporated into new viral particles when they are formed. But nucleotide analogs do not need the chemical processing inside the cell which nucleoside analogs do; therefore, they are potentially able to work in all cells, not only cells which can provide the processing which nucleoside analogs require.
  
  
• Nucleotide analogs are being developed by Gilead Sciences, Inc., of Foster City, California, not only for use in treating HIV, but also for treating CMV and other viruses. At this time it appears that the first nucleotide analog likely to reach widespread human use for treating HIV may be bis-POM PMEA --because it seems to have a better therapeutic window between active and toxic doses than PMEA itself, it can be taken orally, and it is already in human trials. No one knows how bis-POM PMEA will compare with PMPA.
  
  
• It may be hard to tell quickly how well nucleotide analogs are working. For reasons which are unknown, viral load usually shows only modest reductions --comparable to that from AZT -- even when other information suggests that these drugs may be working better than the viral load changes imply. (We would suggest using symptom-reduction trials to study this kind of drug -- small, rapid human trials to see if an anti-HIV drug can help people recover from ongoing AIDS-related symptoms which have been resistant to conventional treatments. For more information, see "Confirmatory" Trials: Symptom Reduction As Efficacy Measure, AIDS Treatment News # 229.)
  
  
• PMPA illustrates some of the problems of delay in AIDS drug development. The newly-published results on protecting monkeys with PMPA were mostly available about a year ago (untreated monkeys were clearly infected at three weeks after exposure to the virus, but the paper reports results for up to 56 weeks after exposure). During this year few people knew about PMPA, which was previously mentioned in only two published AIDS-related articles, both highly technical; many who might have been involved in advancing this line of work were not. (We do not blame Gilead Sciences for the delay, as it was not their study, but a government study -- and Gilead's plate is full with at least six different treatments it is now developing for HIV and related conditions, as well as other treatments for other diseases. The paper was submitted to SCIENCE in April 1995, and accepted in September.) PMPA is now undergoing standard animal toxicology testing, in preparation for human trials as a potential treatment. The first human test, however, will only use a single dose, to determine whether the drug can be absorbed orally (it was injected in the monkey-protection study). If the drug is not orally available, development will probably wait until an oral version can be designed. For years there has been a myth that an injected HIV treatment would not be acceptable in the marketplace; and there is also a regulatory disincentive to proceed immediately with a treatment that must be injected, as the company will later have to start over again if it wants an oral version. These delays do not appear to be anyone's fault. But they do show that we have a problem which needs to be addressed. It is not being addressed today.

References

1. Tsai CC, Follis KE, Sabo A, and others. Prevention of SIV Infection in Macaques by (R)-9-(2- Phosphonylmethoxypropyl)adenine. SCIENCE. November 17, 1995; volume 270, pages 1197-1199.

DOXIL Approved for KS

Background: Liposomes

Liposomes are microscopic globules of fat which can be used to carry certain drugs, achieving a different targeting of the therapy than if the free drug is used. DOXIL, for example, has a half-life in the blood of about 50 hours, compared to about 10 minutes for ordinary doxorubicin. DOXIL tends to concentrate in KS lesions and in cancer tumors more than ordinary doxorubicin; why it does this is unknown, but it may be because lesions and tumors tend to have poor blood vessels. According to this theory, DOXIL remains in the bloodstream for a long time, allowing the liposomes to leak into the lesions.

Sequus Pharmaceuticals uses a special proprietary technology, called Stealth(R) liposomes, in which the liposomes are coated with a chemical to help prevent them from being recognized as a foreign particle in the body and eliminated.

Comments

• AIDSLINE currently has 12 abstracts which mention DOXIL. The evaluations in these abstracts are consistently positive.
  
  
• We have heard good anecdotal reports on DOXIL for several years; this drug seems to be well accepted by physicians and patients, although it is still chemotherapy with serious side effects. But anecdotal information is unreliable, because good news often travels farther than mediocre or bad news, leading to the repeated cycles of "miracle drug" reports followed by disappointment.
  
  
• There has been confusion about the name of the product. Originally the name was DOXIL, while the drug was in early development in the United States. But this name is also used for other purposes in other countries, and to avoid lawsuits, the name was changed to DOX-SL. But then the FDA became concerned that the "SL" in the name could lead to mistakes in which medical personnel thought the drug was for sublingual use (under the tongue) -- mistakes which would result in injury. Therefore the name is now DOXIL within the United States, and will be DOX-SL in other countries.
  
  
• Another drug which is a potential competitor to DOXIL is DaunoXome(R) (liposomal daunorubicin citrate), being developed by NeXstar Pharmaceuticals, Inc. in Boulder, Colorado. DaunoXome has received an "approvable" letter from the FDA as first-line therapy for advanced, HIV-associated KS, but has not yet been finally approved for marketing.
  
  
• Why is DOXIL only approved for patients who have failed or are intolerant to other chemotherapy -- when all the published information is on first-line use, and DaunoXome will be approved for such use? Sequus applied for the failure-or-intolerant indication, apparently because it could get an approval faster. It believes that third-party payers will reimburse first-line use, in view of the strength of the supporting data. And now that there are more data, the company will go back to the FDA to update the indication to include first-line use.

DOXIL Available in Government Trial

An important government study is now recruiting 120 volunteers with advanced KS to compare DOXIL alone vs. DOXIL plus BV (bleomycin and vincristine). Everyone in this trial will get DOXIL; half of the participants will get the other drugs too. Both treatment will be given every two weeks, for a maximum of 25 treatments. There is no charge for participants.

This trial is taking place in the following cities: Albany (2 sites); Birmingham; Boston (2 sites); Buffalo; Chicago (2 sites); Denver (2 sites); Honolulu; Los Angeles (2 sites); Miami; New York City; San Francisco (2 sites); St. Louis.

For more information about this study, which is called ACTG 286, "Comparison Study of Liposomal Doxorubicin with or without Bleomycin and Vincristine for the Treatment of Advanced AIDS-Associated Kaposi's Sarcoma," call the AIDS Clinical Trials Information Service, 800/TRIALS-A.

New Double Vs. Triple 
Antiviral Combination Study, CD4 200-500, 
No Prior Treatment

1. AZT plus ddI,
2. AZT plus ddI plus 3TC, and
3. AZT plus ddI plus nevirapine (an experimental non-nucleoside reverse transcriptase inhibitor).

The study will compare the effects of these different regimens on viral load, CD4 count, and perhaps other "markers" of disease progression. This trial, known as protocol ICC-002, is sponsored by the Inter-Company Collaboration for AIDS Drug Development, a consortium of most of the large companies developing AIDS drug. For more information, or to find the location and contact information for a site near you, patients or physicians can call 800/925-AIDS, from 9 a.m. to 5 p.m. Eastern time.

Internet Censorship: 
Congress Moves Toward Final Decision

1. A broad effort to censor the Internet and online services by barring any material not suitable for small children, or
   
   
2. Giving parents the means to bar access to material they find offensive while preserving freedom of expression for adults.

Recently, some religious right organizations have begun urging the committee to adopt even more restrictive language than the original Exon proposal. As we go to press it remains unclear exactly when the committee will take up this issue, but it is expected to be quite soon. A broad coalition of organizations is encouraging everyone concerned with freedom of speech to contact the committee members and encourage them to oppose all proposals that would censor online communication. Opposition to

Internet censorship has come not only from civil liberties, arts, and libertarian organizations, and from the computer industry, but also from a number of conservatives, including Speaker of the House Newt Gingrich (Republican, Georgia). Many are concerned that online communication will never reach its potential if a lesser standard of free speech applies than for printed publications -- if, for example, literary classics readily available in public libraries could be a felony if placed online.

If you live in any of the states below, your call to your Senator --or to your Representative, if you live in the Representative's district -- is especially important. The Washington D.C. office of any Senator or Representative can be reached through the Capitol Switchboard, 202/224-3121; just ask for the Senator or Representative. The following Senators and Representatives are on the Conference Committee which will decide the issue; we have highlighted the state abbreviations so you can scan quickly for your state. Ask your Senator or Representative to oppose government censorship of the Internet, and leave control of children's access in the hands of parents, where it belongs. Also, call others who live in the following states and ask them to call.

(The information below is from November 20 and November 2 action alerts of the Voters Telecommunication Watch; for more information, see below.) Senators on the Conference Committee which will decide on the Exon Amendment and Internet censorship:

Name, Address, Party and Phone

Arkansas Rep. B. Lambert-Lincoln (D-AR)
501-972-4600

Alaska Sen. Ted Stevens (R-AK)
907-456-0261

Arizona Sen. John McCain (R-AZ)
602-952-2410

California Rep. Carlos Moorhead (R-CA)
818-247-8445

Rep. Elton Gallegly (R-CA)
805-485-2300

Rep. Howard Berman (D-CA)
818-891-0543

Rep. Anna Eshoo (D-CA)
415-323-2984

Colorado Rep. Pat Schroeder (D-CO)
303-866-1230

Rep. Daniel Schaefer (R-CO)
303-762-8890

Florida Rep. Cliff Stearns (R-FL)
904-351-8011

Georgia Rep. Bob Barr (R-GA)
404-429-1776

Rep. Newt Gingrich (R-GA)
404-565-6398

Hawaii Sen. Daniel Inouye (D-HI)
808-541-2542

Illiois Rep. Bobby Rush (D-IL)
312-224-6500

Rep. Dennis Hastert (R-IL)
708-406-1114

Rep. Henry Hyde (R-IL)
708-832-5950

Rep. Michael Flanagan (R-IL)
312-276-6000

Indiana Rep. Steve Buyer (R-IN)
219-583-9819

Kansas Sen. Bob Dole (R-KS)
913-295-2745

Kentucky Sen. Wendell Ford (D-KY)
502-685-5158

Massachusetts Rep. Edward Markey (D-MA)
617-396-2900

Michigan Rep. John Dingell (D-MI)
313-846-1276

Rep. John Conyers (D-MI)
313-961-5670

Mississippi Sen. Trent Lott (R-MS)
601-762-5400

Montana Sen. Conrad Burns (R-MT)
406-252-0550

Nebraska Sen. Jim Exon (D-NE)
402-437-5591

New York Rep. Bill Paxon (R-NY)
716-634-2324

Rep. Daniel Frisa (R-NY)
516-872-9550

Ohio Rep. Michael Oxley (R-OH)
419-423-3210

Rep. Martin Hoke (R-OH)
216-356-2010

Rep. Sherrod Brown (D-OH)
216-934-5100

South Carolina Sen. Ernest Hollings (D-SC)
803-727-4525

South Dakota Sen. Larry Pressler (R-SD)
605-226-7471

Tennessee Rep. Bart Gordon (D-TN)
615-896-1986

Texas Rep. Jack Fields (R-TX)
713-540-8000

Rep. Joe Barton (R-TX)
817-543-1000

Rep. John Bryant (D-TX)
901-382-5811

Rep. Sheila Jackson Lee (D-TX)
713-655-0050

Virginia Rep. Thomas Bliley (R-VA)
804-771-2809

Rep. Rick Boucher (D-VA)
703-628-1145

Rep. Robert Scott (D-VA)
804-380-1000

Rep. Robert Goodlatte (R-VA)
703-857-2672

Washington Rep. Rick White (R-VA)
206-640-0233

Sen. Slade Gordon (R-VA)
206-553-0350

Wisconsin Rep. Scott Klug (R-WI)
608-257-9200

West Virginia Sen. J.D. Rockefeller (D-WV)
303-347-5372

The Voters Telecommunication Watch asked voters in other states to call Representative Newt Gingrich (R-GA), and Senate Robert Dole (R-KS).

For more information, or to learn how else you can help, the VTW action alerts include the following email addresses:

World Wide Web Sites:

• http://www.vtw.org/exon/
  
  
• http://epic.org/
  
  
• http://www.eff.org/pub/Alerts/
  
  
• http://www.cdt.org/cda.html

FTP Archives:

• ftp://ftp.cdt.org/pub/cdt/policy/freespeech/00-INDEX.FREESPEECH
  
• ftp://ftp.eff.org/pub/Alerts/

Gopher Archives:

• gopher://gopher.panix.com/11/vtw/exon
• gopher://gopher.eff.org/11/Alerts

Email:

• vtw@vtw.org (put "send alert" in the subject line for the latest alert, or "send cdafaq" for the CDA FAQ)
  
  
• cda-info@cdt.org (General CDA information)
  
  
• cda-stat@cdt.org (Current status of the CDA)

[Note: Excellent analysis of problems with the telecommunications bill as a whole -- not only the censorship provisions -- can be found at the World Wide Web sites of the Computer Professionals for Social Responsibility, http://www.cpsr.org/nii/cyber-rights/telecom.html, and of the Center for Media Education, http://www.access.digex.net/~cme/bill.html .]