As a doctor and a member of the HIV treater community, I am truly privileged to be here; I am really quite honored to be invited by the International Association of Physicians in AIDS Care (IAPAC) to speak on behalf of both my colleagues and, more importantly, on behalf of my patients. I want to point out, because we have some representatives of the pharmaceutical industry here, that my beliefs on this topic have been labeled as "lunatic," have been labeled as "fringe," as "minority." I would challenge you to consider whether these ideas represent the ravings of a lunatic, or if they should represent the mainstream opinion, or do represent the mainstream opinion, of real-world HIV doctors. So on behalf of my patients, again, I thank you for this platform.
I am going to frame our discussions today in a historical view, which is necessary in order to issue a "call to action." This is a discussion that is focused on the domestic problem -- a problem which, frankly, receives very little attention. We talk a lot about global AIDS. We talk a lot about the South African problem, the Botswana problem, the problem in South Asia, and those are undeniably big problems. In all of the challenges of dealing with the global AIDS problem, and, simultaneously, with all these successes that we have seen in care in the developed world, we have allowed ourselves to think that the problem has been licked. The pictures of people climbing mountains, the pictures of Magic Johnson, who looks terrific, who is terrific, mask or hide the magnitude of the problem. The problem is the nearly 1 million people living with HIV/AIDS in North America, that in a sense I represent, at least half of whom do not have publicly insured mechanisms for AIDS drug access.
Before this looks like some sort of tirade against the pharmaceutical industry, I would like to say I am also a member of the research collaborative called the HIV Out-Patient Study (HOPS) cohort. I am proud to share data that reflect how far we have come in such a short period of time. This is from Frank Palella's now very well quoted research, which was published in the New England Journal of Medicine (Slide 1). The research looks at the mortality of patients with HIV in the United States. This is looking at patients with AIDS, actually a cohort of patients who had CD4 counts less than 100 cells/mm3 at any given time. Back in the pre-HAART era, the pre-protease inhibitor (PI) era, or the pre-azidothymidine (AZT) era, the death rate in this population was about 30 per 100 person-years, and a crude statistical version of that statement says that about a third of the cohort was dying every year.
Something magical happened, of course, to end that era. In those days, of course, an HIV diagnosis was equivalent to having AIDS; you were inevitably going to progress to AIDS and were therefore going to die. As everybody said, the expected survival was about three years. So antiretroviral medications in that era in fact had very limited value. There was some debate, of course, over whether they were useful or not, and in that era in the United States, 30 percent of babies born to infected mothers acquired HIV. Young fellows like me, at the time, became experts not in the treatment of HIV per se, but the treatment of multi-drug resistant Mycobacterium avium complex (MAC), multi-drug resistant cytomegalovirus (CMV), and multi-drug resistant candida.
Again, because of the investment of millions and billions of dollars, and the investment of hundreds of thousands of patient lives and hundreds of thousands of investigator hours, the death rate changed dramatically, as shown in Slide 2. This figure shows Frank Palella's most recent figures from the HOPS cohort. The numbers have changed somewhat because we are not looking at just the AIDS patients; we are looking at the entire cohort. This figure shows all patients with HIV in the HOPS cohort. This represents about 7,000 patients in eight cities, in 10 clinics around the country -- an ethnically, demographically, and socioeconomically diverse cross section of the US population. This shows that the death rate has declined. It has plummeted, and it remains down even up to the last quarter of 2003, and the use of highly active antiretroviral therapy (HAART) -- defined as a multi-drug, multi-class regimen -- has increased to a significant proportion of that patient population. Deaths are down.
Slide 3 shows us that the rates of complication also remain down, despite the fact that preventive measures really have not changed dramatically in this era. Medications and the investment of pharmaceutical companies, the investment of patients who volunteer for clinical studies, the investment of advocates who have pushed us all for access to care and cheap medications, have accomplished this for us, and this is a tremendous evolution in the care and the prognosis of this particular treatment population. Another challenge is to realize that these advances have important implications for the entire issue of drug discovery; what we can do if we simply apply force, if we apply will, and if we apply money. It is an incredible revolution. So, medications save lives. Investment in medications saves lives. Investment in drug discovery, investments from advocates have saved lives.
The current armamentarium includes 22 antiretroviral drugs; 19 distinct drugs and three fixed-dose combinations. It is an incredible tour de force, and compliments to everybody who helped us get this far. The lives of my patients and the lives of your patients, the lives of your clients, your communities, and your customers all benefit from this achievement. These numbers just include drugs that have been approved since 1996, the dawn of the HAART era. In the future we will likely see new co-formulated pills, new classes of medications, perhaps CCR5 entry inhibitors, perhaps a GP120 entry inhibitor, perhaps an integrase inhibitor. The point is that drug discovery will continue if we find ways to continue to provide incentive for that.
We are also in an era where we are talking about the potential for novel strategies, and novel strategies are driven in part by toxicity issues, but also in part by cost issues. I think it is important to bear in mind that those will also impact how we approach treatment strategies in the years to come. I would like to bring this back to my hometown (Slide 4). In Denver, we currently have 8,000 patients with HIV, according to data from the Denver Department of Public Health. Data show that we have saved over an estimated 2,000 lives out of the 8,000 patients who are running around in our state right now. In our little town we have also done a pretty good job of preventing mother-to-child transmission of HIV. There have been four babies born with HIV since the beginning of the HAART era, and three of those babies were born to mothers who were diagnosed post-partum. In the case of the one baby who was born to a known patient, that mother was diagnosed in 1996, in the early AZT era.
What we can do if we get this right? We can save lives. We can improve quality of life. We can prevent HIV infections. The stakes are not just profits. The stakes are not whether or not I get reimbursed. The stakes are lives, and that is something that I think we should not forget. When we talk about policy, when we talk about payer mix, when we talk about fractional shares of market, or new prescription drugs; what we are really talking about is whether people live or they die. In the HAART era, HIV does not mean AIDS and it does not mean death. The average survival of a newly diagnosed HIV patient is probably calculated in decades, not years. In fact, when I counsel new patients, I tell them that they are going to live for decades, live to be old men or women, live to see their children graduate from college, talk about retirement plans. Antiretroviral drugs, of course, in this era have significant value, because we can prevent HIV and AIDS not just in the United States, but elsewhere.
Now we are experts not just in treating complications of AIDS. Actually, I have not seen a case of CMV in five years. So now we have become experts in managing antiretroviral therapy. Mortality is down and, in fact, as was presented at the 11th Conference on Retroviruses and Opportunistic Infections (CROI), the causes of death in our HIV population have also shifted from traditional AIDS deaths to non-AIDS causes of mortality -- cardiovascular disease, non-AIDS malignancies, liver disease. In my practice, the leading cause of death now is suicide because of my patients who have had ongoing psychiatric issues, but not Pneumocystis carinii pneumonia, not MAC, not wasting.
The problem, however, is that the new incident cases continue. On this issue, we have not done a very good job at all. In fact, we have done a terrible job as providers, as educators, as industry, in preventing new cases, because the message has been forgotten. We have dropped our guard. We have become complacent with regard to HIV. We have become complacent with regard to prevention, and that means now that more women, more heterosexuals, more people of color, more people who do not speak English are acquiring HIV, and that provides further challenges to us as a treatment community in providing care and access to care. As this demographic changes, it becomes not just an interesting epidemiological point but, in fact, an ethical imperative to address the concerns of the changing demographics of our population. The consequence of this success in therapy, as Patrick [Clay] alluded, is that patients live longer. That is a good thing, because that means we allow people to live life without having HIV as the veneer through which everything else appears. It also comes with some costs. The costs are long-term treatment, long-term engagement with medical care, long-term issues with long-term toxicities, and the long-term financial and physiological costs of having HIV and its therapies.
What we have seen in the last decade, which is about the period I have been providing HIV care, is an unprecedented evolution, and arguably revolution, in the care in the medical industry around HIV. Again, in Colorado we have, roughly speaking, 8,000 infected individuals. About 4,000 of these individuals are on antiretroviral therapy. Our AIDS Drug Assistance Program (ADAP) is bankrupt, with ever-increasing demands, with about a 5 percent growth in ADAP requests per year and flat funding over the last three years. A year ago we had zero patients on our waiting list; we now have 220 patients. Twenty-five percent of the people on the national ADAP waiting list reside in my little state.
There are also challenges ahead. These challenges present ethical, moral, and medical issues for us, such as the ever-increasing prevalence of primary transmitted drug resistance, an increasing prevalence of pre-existing drug resistance, the increasing prevalence of resistance in patients who are already under care. In my state, a decreasing amount of physician reimbursement has led to the closing of three of our large family practices that provide specialty HIV care.
So, what does the future hold? This is the "call to action" part. My view of the future is that HIV and AIDS will ravage the developing world. If you want to visit South Africa and you want to go on safari, do it soon, because the face of southern Africa, the face of East Africa, and the face of Asia will change irreversibly in the decade to come unless we get off our butts. In fact, the differences between the haves and the have-nots will only increase in the decade to come. In the developed world, there will be more patients living with HIV, and the increasing frequency of either transmitted or existing drug resistance, and, therefore, there will be increasing and significant need for medical and medication support. Unless we get off our butts, these problems will not improve.
There are a couple of potential views on the future of medications. I think medications will become less expensive, certainly AZT is going off patent, which will help in that regard. We are already seeing a dramatic trend toward easier-to-take medications. I think new medications have made a significant change in my patients' ability to adhere to their regimens, and thus increased their quality of life, and I think that investment was worth the time and effort, though maybe I am biased. However -- this is the big "however" -- I think recent price changes really challenge our resources and challenge the way that we must think about how we deliver care not only to this population, but also to other patient populations. I do think we have a dramatic problem with our public policy at times, and sometimes that public policy is downright irrational. Because of these issues, I think it becomes an ethical imperative for us as physicians, whether we work in industry or the public sector, to consider the ethical principles involved in these kinds of issues. I have been called a lunatic because I think that there are ethical principles that should guide opinion around these points.
I do believe that we will see some of these new drug classes actually make it to the market, and these will offer unprecedented hope for patients who right now do not have hope. I think back to the 1997-1998 era, to patients who had multi-drug resistant virus and are now dead; only wishing that they could have seen a glimmer of hope for some of these new medications. Once again, I value and welcome the support from the pharmaceutical industry in bringing these new drugs forward.
I have alluded to this before, but I think that there will be new strategies to administer therapy that will decrease total drug exposure and decrease total drug cost. Again, this poses some difficult questions for the pharmaceutical industry in terms of creating an incentive for profit, but it also provides us a way of providing care and access to care to people who might not otherwise be able to afford it. Unfortunately, there will be no cure in my lifetime, and my fatalistic prediction is that there will be neither a therapeutic nor a preventive vaccine in the next two decades. We have to stop hoping for these kinds of handouts and start making some choices, or at least have a voice around these choices.
This "call to action" is based on the principle of an ethical imperative to save peoples' lives. Prevention strategies have to improve. This means that the Bush Administration has to forget about the idea that condoms increase abortions, and think about the ethical imperative that has been demonstrated in country after country -- that condoms and latex save lives. Latex prevents HIV, and this runs counter to the Bush Administration's healthcare policy. This runs counter to the Vatican's policy. That must change, and doctors have to stop being quiet and acquiescent on that point. This has been a discussion that might otherwise seem to have an anti-pharmaceutical industry slant, but continued investment and continued profit for the pharmaceutical sector is the key to further drug discovery, and that must be fostered in a way that is productive.
As physicians, we must begin to consider the mechanisms for overcoming barriers to access to care. This is the key issue. In fact, access to care does not just mean medications, it does not just mean condoms, it does not just mean latex, but it also means appreciating the very complicated issues of the political, cultural, and economic climate in which all of this is delivered. Our failure to appreciate that during the 13th International AIDS Conference in Durban, South Africa, contributed to the continued intransigence of the South African government, preventing access to care. If we get it right, we can do something that is really unprecedented, which is that we can save lives around the world. We might be able to change the way that governments and cultures around the world interact with one another. But doing that is going to require unprecedented collaboration between all sectors -- between government and nongovernmental organizations, between community and industry, and between patients and doctors.
I think we are standing at the precipice where we might be able to do that. Ironically enough, this possibility may have been triggered by Abbott Laboratories' decision to increase the price of ritonavir (RTV). In a sense, we owe Abbott Laboratories a little scintilla of gratitude for catalyzing that discussion.
It is an ethical principle based on ethical imperative. I was very fortunate a week ago to get my 10 minutes of audience with Archbishop Desmond Tutu when he was coming through Colorado lecturing on AIDS, drug pricing, and access to care. He articulated something that I would like to use as a framework for thinking about how to move forward, and I am afraid I will completely destroy his words. But he talks about taking care of family. Family is not just your genetic family or your first-degree relatives. Family is the entire planet. It is the entire community. I used to do a lot of volunteer relief work in Guatemala, and we talked about comunidad, which does not just mean community, it encompasses a very large sense of caring both for people you know and people you do not know. I would like to pause at the idea that we must consider the possibility of comunidad and family in our communities. HIV communities are defined broadly as industry, the government, the research community, the medical community, the patient community, and the activist community. The question really is, "If you view the other members of that community as your family, are the strategies that you are developing consistent with how you would take care of your grandmother?" If the answer is yes, then you are proceeding on an ethically sound principle. If the answer is no, the next question is whether you should reconsider that policy.
HIV patients are not patients who have allergic rhinitis, and while the pharmacoeconomic principles that guide drug discovery often are used to explain pricing strategies and discovery principles and other treatment niches, I do not think those principles necessarily apply. HIV is a life-threatening disease. HIV therapies in a diverse formulary for HIV medication save lives and clearly improve quality of life. So the models have to be rethought. We need to challenge the way that we think about this, and I challenge the pharmaceutical industry to rethink, consider what we are doing here. Can we do something which is proactive and creative, and which can actually change the entire healthcare industry for the better?
I believe very strongly, although it is debated, that access to life-saving care is not just a good idea, not just something that makes money, it is actually a human right. That may seem a radical idea, but in fact it is not. Unless the idea is established in our principles that access to care is a human right, guys such as me get labeled lunatics. I happen to think that it is not a lunatic idea that access to care is a human right, and I would like to think that physicians who believe so are not lunatics and are not representative of the fringe minority. That said, access to profit is probably also a right. If you subscribe to capitalism as the engine by which we get new medications, the engine that stimulates discovery, then that is an important right. But that right has to be balanced against the other right, and those are the difficult waters that we have to traverse in order to come up with the policy that actually makes good common sense, that will actually save lives and prevent patients in ever-increasing numbers from being on waiting lists for life-saving medications in my state and, indeed, in this country.
In an incredible statement, a Senator from my state who happens to be on the Appropriations Committee says that HIV patients in the state of Colorado are already getting more assistance than they deserve. It is an amazing fact that people who argue for access to care as a human right get labeled lunatics, get labeled as being too personally involved in the care of their communities. This is not acceptable, nor is complacency. Complacency only leads to further prolongation of this problem, and the complacency of physicians will only lead to further problems with access to care, and to increases in the cost of care. It will jeopardize the possibility for future drug discovery, and most importantly, will jeopardize lives. We have already seen patients on waiting lists in two states die while waiting for access to life-saving care, a situation that is frankly unbelievable in this country.
Doctors have to be more involved and cannot just sit on their butts looking for a handout. We are operating in the threshold of the period where we must begin to consider the ethical imperatives and the ethical principles by which we look at this disease and the communities we serve. I believe this very strongly, and I think it is a very positive step for IAPAC and for the other care provider organizations to discuss the fact that physicians and other healthcare providers have the moral obligation to become involved in this issue. Silence is complacency. Silence is an acquiescence to the status quo, and if you like the status quo then silence is fine.
I happen to think that the 220 or 250 patients in my state who are on waiting lists to receive life-saving medications do not think that the status quo is fine. I would encourage all of us to consider those ethical principles. This is an ethical imperative and silence is not acceptable.
Finally, I would like to tell you about my dear and longest-living patient, Donny. I met Donny in 1995; if you remember the timeline, this was right at the dawn of the PI era. He had progressive multifocal leukoencephalopathy when I first met him. He had a CD4 count of 30 cells/mm3. He had a son who was my daughter's age. In fact, we are the same age. Donny now has a CD4 count of 700 cells/mm3. He is on a drug holiday. He is a success, by the way, of full-dose RTV therapy. He was one of the first patients in the AIDS Clinical Trials Group (ACTG) 315 study, and he is one of the many faces of HIV representing both the successes of therapy and the challenges for all of us, because he has been homeless for most of this time. I used to meet him under a bridge to do his pill counts, to make sure that he was taking his medications. Once again, we talk about public policy, we talk about involvement, we talk about ethical principles, but ultimately it all boils right down to the fact that we are talking about peoples' lives; Donny's life and many other patients' lives, and their families and the communities that are affected by what we do or fail to do.
Benjamin Young is a Clinical Instructor in the Department of Medicine at the University of Colorado Health Sciences Center.
Back to the May 2004 Supplement issue of IAPAC Monthly.