AIDS Treatment News
1592 Adult Compassionate-Use
As this issue went to press, we received an announcement of the open-label protocol for 1592 for adults (the program for children was previously announced; see AIDS Treatment News /content/art31510.html/content/art31510.html#275). The number of patients who can enroll will be seriously restricted because of limited drug supply, and limited human experience with the drug. Also, the complete list of sites for the adult program is not yet available -- and many of the sites are not ready at this time, because they still need IRB approval. A central IRB is in place for those sites that need one.
To be eligible for the 1592 open-label adult program (Protocol CNAA/B3008), persons must be at least 13 years old, have a CD4 count under 100 and viral load at least 30,000 copies "within 60 days of registration and while on currently acceptable combination regimens," have been treated with at least two nucleoside reverse transcriptase inhibitors and one protease inhibitor, or not be receiving treatment due to intolerance to at least two different regimens, one of which contains a protease inhibitor (and be intolerant to at least one nucleoside reverse transcriptase inhibitor and one protease inhibitor). Also they must not qualify for an enrolling study of 1592.
There are other exclusion criteria, the most important of which seem to be pregnant women or women who are breastfeeding, or "patients with hepatic failure evident by grade 3 or 4 hyperbilirubinemia and AST >5 x upper limits of normal." 1592 should be administered "as part of a combination antiretroviral regimen, including other antiretroviral agents which the patient has never received," but otherwise the patient "should take as few concurrent medications as medically feasible." The antiretrovirals used in the combination may include those from other compassionate use programs, if approved by both Glaxo Wellcome and the other company.
Physicians interested in enrolling patients should call 800/501-4672.
Returning to Work:
Five articles on disability and medical benefits, and planning for returning to work, were published in WORLD (the newsletter of Women Organized to Respond to Life-Threatening Diseases), July 1997. All were written by Thomas P. McCormack, a benefits expert and author of THE AIDS BENEFITS HANDBOOK (Yale University Press, 1990). They examine some of the options for avoiding loss of disability and/or medical benefits as a result of working.
The articles look at:
Federal AIDS Policy Issues Todayby John S. James
While in Washington in July for an FDA advisory committee meeting on viral load, and a National Institutes of Health meeting of the AIDS Clinical Trials Group, we also checked on some of the Federal HIV/AIDS policy issues developing in Congress and in the Clinton Administration -- especially those concerning AIDS treatment. Much is happening; and while timely information about Federal activities usually does reach some of the major AIDS organizations around the country, the background seldom gets through to the general public. By the time an emotional issue becomes a political football and gets media coverage, it is usually too late for the public to be involved except as supporters or opponents of pre-determined positions. Washington would suffer less of its famous isolation from how most people think and live, if non-specialists could learn earlier what was going on, and become involved in what matters to them while there is still flexibility in shaping the objectives, strategies, and decisions.
Today in Washington AIDS funding is doing better than we would have expected -- thanks more to Republicans as well as Democrats in Congress, than to the Clinton Administration. But there are many reasons to be concerned. It is clear that modern treatment is saving many but not all lives, that those with the best access to medical care are most likely to live, and also that treatment is cost-effective, keeping people productive and working instead of disabled and requiring hospitalization or other expensive care. But while many cannot get good care for economic reasons, institutions are often competing not to help solve the access problems, but to avoid being the payer of last resort. And there have been some serious divisions and questionable strategies within AIDS political organizations.
This article attempts to outline some (not all) current Federal AIDS issues, especially those which are treatment and access related, so that our readers can understand what they are. Sometimes there are bitter fights behind the scenes within or between AIDS organizations, and here we have tried to avoid taking sides -- which is made easier by the fact that we are usually too far from these inside-the-Beltway battles to have aligned with a side or developed a firm position. But we could not banish our views entirely, since some of the material would be difficult to communicate or understand without the perspective provided by some viewpoint or other.
New information that treatment is saving lives.On June 14, the U.S. Centers for Disease Control released updated information showing a 19% decline in AIDS deaths in the U.S. The decline among different groups clearly reflected inequalities in treatment access: a 22% decline in deaths among men vs. 7% among women; and 28% among whites vs. 10% among African Americans and 16% among Latinos. (Where medical care is more widely available -- as in British Columbia, with the Canadian health system -- deaths have dropped 50%. In some leading medical practices in the U.S. and elsewhere, the recent drop may be much larger than 50%. While exact comparisons between different situations may be difficult or impossible, the pattern is clear that access to medical care for HIV disease is now a life-and-death issue.)
We must also remember that the new combination antiretrovirals do not work for everybody, and it is not clear how long they will work when they do. What we know today suggests that usually, the first antiretroviral treatments a person uses may be most likely to work, since it is harder to treat those who have already had extensive antiretroviral treatment which failed. Therefore, it is important to do everything possible to improve the chances that the first treatment will be successful. However, there are many individual cases of persons who have had very good results with new regimens after prior treatment failure.
Also, some antivirals have much less of a problem with viral resistance than others. And there seem to be emerging hints that certain treatments may have some benefit even after they have lost much of their ability to keep a person's virus under control. Much more needs to be learned about how to use even the existing drugs for patients who have had treatment "failure" (that is, failure to keep the viral load suppressed).
And much more attention is needed to developing new approaches -- from new classes of antiretrovirals such as integrase inhibitors, to different kinds of treatments such as immune-based (or even immune-suppressive) therapy, to more attention to occasional accidental hints that some treatment may be working through a completely unknown mechanism. (Today such observations usually are quickly abandoned, since they are considered unreliable if there is no known mechanism. Instead, such accidental discoveries should be perhaps the highest priority for research, because of the possibility of developing new classes of treatments -- which already have shown proof of principle in humans, even before organized research and development begins).
The policy bottom line is that AIDS research remains as necessary as ever for saving lives in the future. Unfortunately a serious problem today is that there are few major new drugs in the pipeline for the next two to three years -- due in large part, we believe, to deficiencies in earlier stages of the drug-development process, not just to the natural difficulty of medical research. This situation needs much more attention from activists and the public, as well as from professional researchers and policy specialists.
Progress in ADAP fundingThe AIDS Drug Assistance Program (ADAP), run by the states with Federal funding from the Ryan White CARE Act and usually state funding as well, is intended to help persons who are uninsured or underinsured. It is a major component of access to care for those who may be employed and who therefore are probably ineligible for Medicaid, but could not afford treatment otherwise (antiretroviral combinations which include protease inhibitors can cost $15,000 a year). ADAP is also paying for drugs for many who are poor enough for Medicaid, but are not judged "disabled."
In the last two years a financial crisis has developed in the ADAP programs of many states, because with better treatments available today, more people are choosing to get treated, and to learn their HIV status so that they can get medical care if necessary. Also, the new drugs are more expensive, and clearly need to be used in combination with other antiretrovirals, further increasing the financial demands on the programs.
During the last year, much work has been done in documenting how ADAP programs are operating in every state,(1) and in projecting future needs based on current data on utilization trends.(2) A conservative estimate is that $132 million in additional Federal funding will be needed for next year (the ADAP fiscal year begins in April). Today, only three states (California, New York and North Carolina) cover all FDA- approved HIV drugs for everyone who needs them, while three (Arkansas, Oregon, and South Dakota) do not cover protease inhibitors at all.(3) (Nevada, also listed in the report as not covering protease inhibitors, has just decided to contribute state funds which will allow the program to do so. California did not cover all of the drugs when the report was written, but now does.)
In the last year, 35 states imposed at least one emergency measure, such as waiting lists, reducing the list of drugs covered, or transferring money from other health programs to pay for the drugs. Recently we heard that about 10 states are heading for a crisis this year, in which treatment will be refused to many who need it and who qualify for the programs set up by those states.
On July 15 the House of Representatives Labor-HHS Appropriations Subcommittee approved a funding increase for the full $132 million conservatively projected to provide doctor-prescribed treatments for those who are eligible for the ADAP program and likely to use it next year -- despite the fact that the White House had failed to send Congress a request for the money, which Congress had asked for. On July 22, however, a Senate subcommittee approved only $50 million. The difference will probably be resolved in a conference committee -- meaning that a lot of work -- and political unity -- from AIDS organizations will be required.
It is also important to know that states vary greatly in how they fund and run their ADAP programs. While intended as a Federal partnership with the states, about 20 states put in no money of their own, and rely on Federal funds entirely. This is a big part of the reason why some states have much more restrictive programs, or have run out of money and had to impose emergency restrictions.
Another difference between states is that, while ADAP is funded primarily from Title II of the Ryan White CARE Act (which provides money to the states depending on their number of AIDS cases), some states (for example, New York) also use some of their Title I money for ADAP, while others (for example, California) do not (although some cities use Title I money to fund treatment in other ways than by direct transfer to the state ADAP program). Title I is for relief to metropolitan areas heavily impacted by the epidemic; therefore, states with no such cities do not receive Title I.
ADAP and the "FASA" DisputeA political conflict has developed within the ADAP Working Group, one of the organizations which was instrumental in getting favorable consideration from Congress for the ADAP program. The dispute concerns a provision in a law called FASA (the Federal Acquisition Streamlining Act). This provision, which is part of existing U.S. law but has never been used due to industry opposition, would expand a Federal discount pricing schedule currently used by the Veterans Administration, the military, and some other government agencies, so that state governments and some public clinics could use it as well; it would apply to purchases of furniture, equipment, and much else besides drugs. The pharmaceutical industry is strongly opposed -- as are many suppliers who would lose business if state governments and public agencies could buy supplies at the Federal discount instead of buying from them. (This FASA provision should not be confused with the deep discount "PHS pricing" of pharmaceuticals, which is already in use by some but not all ADAP programs.)
The ADAP Working Group is a coalition of AIDS community organizations and pharmaceutical companies. It is funded by membership contributions by all of the organizations, with industry paying higher dues; but the community organizers may have more day-to-day influence on its operation, because the industry people are more constrained by the rules and policies of their companies. On the whole, this structure has worked well, greatly contributing to the success of increasing ADAP funding by bringing together two very different groups which each has its own interest in getting the drugs paid for.
The pharmaceutical industry strongly wants Congress to repeal the FASA provision that would extend discount Federal pricing to state governments and some other public agencies. Many companies will not discuss the issue in the ADAP Working Group, on the grounds that company employees could be violating antitrust laws if there is any discussion of drug prices or pricing programs when representatives from more than one company are in the room; they say these discussions must be with individual companies outside of the Working Group. Most but not all AIDS organization which are involved with this issue strongly support the FASA provision -- or at least want to hold hearings on it before it is repealed -- since it might lead to lower drug prices to ADAP programs, and therefore access to care for more patients (some dispute this, saying that companies will raise prices to compensate for expansion of the Federal price schedule, and that there are other technical reasons the program might not work well). They are also concerned that the White House and some members of Congress are unlikely to support the ADAP Working Group's future requests for money, if the pharmaceutical industry, which receives the money which is spent through ADAP, refuses to help make the Federal funds go as far as possible in a time of budget cuts.
Our main concern is that this dispute has become a partisan one, threatening the unity which is necessary if AIDS organizations are to be effective in supporting treatment access. AIDS should be nonpartisan; but over the years most AIDS political organizations have unfortunately been much closer to one political party, the Democrats. Since the Republicans now control both houses of Congress, their support is critical; we are fortunate that the ADAP Working Group is nonpartisan, that the Log Cabin Republicans (a group focused primarily on gay issues) and others have helped organize the Republican support it needed. But the Log Cabin Republicans also strongly support industry in its efforts to repeal the FASA provision, and this has led to conflict between it and other AIDS organizations in the ADAP Working Group. The conflict could become a serious threat to the effectiveness of AIDS work in Congress, especially since the AIDS community in Washington has too little representation on the Republican side.
On July 11 a Senate subcommittee voted to repeal the FASA expansion provision. It did not consider a government- proposed compromise to retain the discount pricing for states and public agencies for drugs for life-threatening conditions, since one member of the subcommittee, who had been expected to introduce that compromise, decided not to do so. (The compromise did have one harmful element, in that for two years it would have singled out HIV for the lower prices, as a kind of trial run -- which could have created understandable resentment by other disease advocates, since all life-threatening diseases should have the lower prices equally.)
Comment: What is most likely to happen now is that Congress, apparently paid off by industry, will repeal the FASA provision before the public even knows about it; hearings which were supposed to happen this year did not take place. But if this issue does have a future, we would hope that the AIDS community would keep it out of the ADAP Working Group, which is an effective but fragile coalition of two interests which are irrevocably split on this issue. FASA should be used to help build vitally necessary coalitions with other disease groups, whose interests here are identical to those of the AIDS community -- not to split apart a productive coalition which we already have.
On the larger politics around ADAP, we have asked participants why the Republican-controlled Congress has been much more helpful on ADAP funding than the Democratic Administration. The four answers we have heard are (1) many people in both parties have had personal contact with someone with AIDS, and this is more influential than party affiliation; (2) ADAP is strongly supported by industry, with which Republicans are usually aligned; (3) the ADAP Working Group and the Log Cabin Republicans have done their homework well and kept the issue prominent; and (4) the rules of Congress are such that the (Democratic) Administration would have had to find an "offset" -- take money away from some other program in the Health and Human Services budget, to pay for the ADAP funding increase -- while the (Republican controlled) Congressional subcommittee had somewhat different constraints.
Other AIDS fundingMany other AIDS programs were increased about 5 percent in the House subcommittee; a Senate subcommittee followed the House levels in some cases, and proposed different funding in others. For NIH AIDS research, the House proposed an increase of 4.8% --considerably more than proposed in President Clinton's budget of February 6; we do not have a Senate figure for NIH research. For housing, the president and the House and Senate subcommittees have all agreed on an 8 million dollar increase in HOPWA (Housing Opportunities for People with AIDS), about 4%. For AIDS prevention at the Centers for Disease Control, the House proposed only a 0.8% increase (far below the president's request), while the Senate proposed 4.8%.
The next step for the public to be involved will be talking to their members of Congress during the August recess, which lasts for the entire month; during the recess it will be important to urge Senators to raise the $50 million ADAP increase to the $132 million appropriated by the House, as otherwise as many as 8,000 people may go without the treatment they need. After the full Senate and House have voted, the legislation will go to a Conference Committee to work out differences between the two versions. It is not yet known who will be on the Conference Committee, but they will probably be members of the Senate and House Appropriations Committees. Members of the public should contact their Senators and Representative at that time, to support the highest AIDS funding levels, whether those are from the House or the Senate (see "How to Be Involved," below).
FDA reformSince the Republicans gained control of Congress in January 1995, there have been a number of proposed laws to greatly change how the FDA evaluates new drugs and medical devices (here we will focus on drugs; the devices situation is often different). Supporters usually describe these proposals as ways to make the FDA more efficient and get new drugs to patients faster; opponents are likely to describe them as giveaways to industry which weaken standards and endanger the public health. No law to change the FDA emerged from the last Congress (1995 and 1996); this year, less extreme bills are moving more rapidly, and it is likely that some law will be passed this year or next. (An example of an extreme measure -- which was considered last year but not included in the bills this year -- provided for automatic drug approval in some cases if the FDA missed deadlines written into the bill by Congress.)
Complicating the legislation around FDA reform is one issue on which everyone agrees -- the renewal of the Prescription Drug User Fee Act of 1992 (PDUFA), which allows the government to bill pharmaceutical companies for evaluating their drugs, and use the money to hire extra reviewers and make other improvements so that the evaluations can be faster. Companies are happy to pay, because the money they save by a faster review is far greater than the fees. Patient advocates are also supportive, because the drugs can be evaluated faster without any lowering of standards. However, PDUFA must be reauthorized by the end of September, or reviewers may soon have to be laid off -- which could seriously delay new AIDS drugs like 1592 and DMP 266 when they go for FDA review.
The problem now is that the PDUFA renewal legislation has other provisions attached, to change the operation of the FDA. Some of these provisions have wide agreement and are not an issue; but others have been added to the bill although consensus has not been reached.
What are some of the FDA reform provisions now in dispute? A June 11 letter from Health and Human Services Secretary Donna Shalala to Senator James Jeffords of Vermont (who is Chairman of the Committee on Labor and Human Resources) discussed the areas of agreement and disagreement in S. 830, the Food and Drug Administration Modernization and Accountability Act of 1997. She noted that the bill then contained "approximately 20 provisions that represent significant consensus reforms. Among the provisions that we all agree on are those that set forth the Agency's mission, codify reforms to the regulation of biotechnology products, provide expedited authority for the adoption of third party performance standards for device review and for the classification of devices, and streamline submission requirements for manufacturing changes and marketing applications for drugs and biologics."
But the letter also listed five non-consensus provisions: "(1) lowering the review standard for marketing approval; (2) allowing distribution of experimental therapies without adequate safeguards to assure patient safety or completion of research on efficacy; (3) allowing health claims for foods and economic claims for drugs and biologic products without adequate scientific proof; (4) requiring third party review even for devices that require clinical data; and (5) burdening the Agency with extensive new regulatory requirements that will detract resources from critical Agency functions without commensurate enhancement of the public health."
A major FDA reform issue -- not addressed in the non- consensus item list above because it was not yet in the bill -- concerns whether pharmaceutical companies should be allowed to promote to doctors uses of approved drugs which are based on scientific studies, but have not been approved by the FDA. We consider this a difficult issue, because it is impossible to know in advance whether or not the benefit will outweigh the harm. Most AIDS organizations which have a position on the matter have come from the consumer-protection camp, and therefore oppose letting companies promote such "off label" uses of their products.
Those opposed to off-label promotion argue that the system should be and has been changed to make it easier for a company which has a legitimate new use for its product to bring the data to the FDA and get the drug officially approved for that use. Otherwise, drug sales persons could use scientific studies that might not have been well reviewed and may be erroneous, to increase their income and advance their career by selling drugs which do more harm to the patient than good. Also, companies may have little incentive to do the research to thoroughly test the new use, if they could promote it anyway. And the current proposals do not address reimbursement problems, which will often leave patients to pay by themselves for the drug their doctor prescribed, if their health plan says it is not convinced by the available evidence.
On the other hand, drug companies usually know more about their drugs than anyone else; and there are probably many cases where they know about uses which would be very important to some people, but under the current system never come to widespread attention. Overworked doctors keep giving standard remedies, and when these do not work the patients are out of luck. Professional medical associations have unfortunately not filled this breach, and they do not seem ready to do so; perhaps the problem is that medicine is (and generally should be) a conservative profession, and while doctors do write many prescriptions off-label, it might not be a good career move to actively seek out, develop, and promote new opportunities for doing so. Meanwhile pharmaceutical companies are far less likely to do anything with potential off-label uses, if it means spending considerable money up front for research and a new FDA review with no assurance of gain, than if it means giving some reprints to their sales force and seeing their sales and profits rise immediately. Potential beneficial new uses that go nowhere must be recognized as a major though largely unknown cost of the current system.
Note: As this issue went to press, BIOCENTURY newsletter reported on July 28 that a compromise has been reached to allow a company to disseminate peer-reviewed literature, provided that it certifies that it will apply for supplemental FDA approval for that use of the drug, or submits a plan to do so. The approval could be revoked if the company fails to follow through. Also, the FDA could insert a statement into the literature package distributed by the company.
MedicaidWe cannot cover Medicaid issues here in detail, but want our readers to realize their importance. Medicaid is by far the largest source of public funding for AIDS care. According to a briefing paper from the Gay Men's Health Crisis in New York, it accounts for about two thirds of the total -- compared to only 15% from the Ryan White CARE Act, 13% from Medicare, and less than 2% from other programs.
Many states are now experimenting with restructuring Medicaid (called Medi-Cal in California) in various ways. Some of these changes could improve the program -- but other changes could strip away protections and make it impossible for persons with serious illnesses and low income to obtain adequate care. The central concerns for activists in Medicaid relate to the state-by-state specifics of program changes, which are usually implemented under Federal waivers which release states from certain legal requirements, with the intent of allowing the states flexibility so that they can develop more efficient programs. It is critically important that Federal oversight of these state experiments be maintained.
A very important proposal, suggested by the AIDS Action Council and supported by Vice President Al Gore, would be to change the Medicaid rules so that people do not need to become disabled by HIV disease before they can receive treatment for it. (Today, only a few people with HIV qualify for Medicaid without disability, through other programs.) Such an approach might save as much as it costs, or even more, by keeping people healthy and avoiding expensive remedial care; however, it is difficult to predict government funding implications. The U.S. Department of Health and Human Services is currently doing a feasibility study requested by Vice President Gore.
The "HIV Prevention Act of 1997"We have not reviewed this legislation in detail. According to an analysis by the Gay Men's Health Crisis, it would require states to implement and pay for many testing and reporting changes which have long been rejected by public health authorities. States which did not pass the laws required would be punished by losing Medicaid funds. Unfortunately this bill is supported by the American Medical Association.
Needle exchangeOn this notorious issue it is entirely clear that needle exchange programs can reduce HIV infections, without increasing drug abuse. The lack of adequate needle exchange programs has led to thousands of unnecessary HIV infections, according to a study by University of California researchers published in June 1996. Needle exchange has been supported by study after study, and the American Medical Association, the U.S. Conference of Mayors, and many others have called for lifting the current Federal funding ban. A 1996 public opinion survey found two- to-one public support for distributing clean needles to slow the spread of HIV. What is holding back wide use of this public-health tool is politics resulting from the war on drugs.
Needle exchange is not a solution by itself, but a component which can work with other programs, including medical and social services for injection drug users, and drug-treatment services upon request. It can bring into prevention and treatment many people who would not be reached in other ways.
Another approach to reducing HIV infection is decriminalization of needle possession. Many states already allow hypodermic needles to be sold in pharmacies without a prescription -- and Connecticut just changed its law to do likewise. If drug users could carry one needle for their own use, without fear of prosecution for doing so, then they could avoid the need to use whatever needle was available at the place they get the drug. Drug paraphernalia laws probably also need to be changed for this to work; the American Medical Association "strongly (encourages) state medical associations to initiate state legislation modifying drug paraphernalia laws so that injection drug users can legally purchase and possess syringes."
A demonstration calling for lifting the ban on Federal funding for needle exchange has been called for September 17, at the Department of Health and Human Services in Washington D.C. For more information, see http://www.safeworks.org/savelivesnow/.
International AIDS issues.At this time U.S. funding for international health and development work is being increased, and AIDS is sharing in that. There have been large decreases in recent years, however; the hope is that this year's Congressional action could bring the AIDS total as high as $121 million, which is where it was in 1993.
How to Be InvolvedIf you want to work on Federal issues, you can sign up with one or more organizations which will send you background information, and action alerts when it is important to contact your representatives. Some of these organizations are: