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AIDS: The Research Challenge

This report examines the AIDS research program that NIH, the nation 's foremost biomedical research institution, has developed in response to the epidemic of HIV infection and its most serious clinical manifestation, AIDS. The report focuses on the challenges facing NIH in the present struggle to understand, manage, and control the disease and presents conclusions and recommendations regarding the present status of the program and its future directions. Because the epidemic will continue to grow, NIH is now faced with institutionalizing its many AIDS research activities and melding them into a well-planned, well-managed research program that takes a comprehensive, long-range view of the epidemic. This report addresses the tasks that must be completed to accomplish that mission. First, however, this chapter discusses the reasons why NIH should continue to make AIDS research a high priority and convert it into a long-term program. It also reviews the latest epidemiological trends and discusses the problems for NIH's clinical research effort caused by inadequacies in the nation's health care delivery and financing system. The rest of the report examines program-wide (Chapter 2 and Chapter 4) and specific (Chapter 3) adjustments recommended by the committee for the future of the program, given present scientific opportunities and public health needs.

UNIQUENESS OF THE EPIDEMIC

AIDS is the first major life-threatening infectious disease epidemic faced by the United States in decades. It is also the first such epidemic since the advent of modern biology and the growth of the national biomedical research enterprise. Caused by the human immunodeficiency virus, AIDS is a fatal disease for which there is no known cure or vaccine. Those affected remain infectious for years, during both a symptomatic stage as well as an asymptomatic phase that precedes manifestation of the disease. Because HIV specifically targets and kills certain critical cells of the body's immune system, the immune response of infected individuals eventually fails. They cannot eradicate the virus that infects them, and they become chronically susceptible to life-threatening infections by a myriad of other microbes, generally succumbing eventually to one of these opportunistic invaders or to certain forms of cancer to which they are also especially susceptible.

At the beginning of the epidemic, AIDS was especially prevalent among socially stigmatized members of society–homosexual men and users of intravenous drugs. A decade into the epidemic, the disease is slowly moving into a new subpopulation–inner-city minorities who also live on the margins of mainstream America. Many observers have attributed the slowness of the initial federal



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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH 1 AIDS: The Research Challenge This report examines the AIDS research program that NIH, the nation 's foremost biomedical research institution, has developed in response to the epidemic of HIV infection and its most serious clinical manifestation, AIDS. The report focuses on the challenges facing NIH in the present struggle to understand, manage, and control the disease and presents conclusions and recommendations regarding the present status of the program and its future directions. Because the epidemic will continue to grow, NIH is now faced with institutionalizing its many AIDS research activities and melding them into a well-planned, well-managed research program that takes a comprehensive, long-range view of the epidemic. This report addresses the tasks that must be completed to accomplish that mission. First, however, this chapter discusses the reasons why NIH should continue to make AIDS research a high priority and convert it into a long-term program. It also reviews the latest epidemiological trends and discusses the problems for NIH's clinical research effort caused by inadequacies in the nation's health care delivery and financing system. The rest of the report examines program-wide (Chapter 2 and Chapter 4) and specific (Chapter 3) adjustments recommended by the committee for the future of the program, given present scientific opportunities and public health needs. UNIQUENESS OF THE EPIDEMIC AIDS is the first major life-threatening infectious disease epidemic faced by the United States in decades. It is also the first such epidemic since the advent of modern biology and the growth of the national biomedical research enterprise. Caused by the human immunodeficiency virus, AIDS is a fatal disease for which there is no known cure or vaccine. Those affected remain infectious for years, during both a symptomatic stage as well as an asymptomatic phase that precedes manifestation of the disease. Because HIV specifically targets and kills certain critical cells of the body's immune system, the immune response of infected individuals eventually fails. They cannot eradicate the virus that infects them, and they become chronically susceptible to life-threatening infections by a myriad of other microbes, generally succumbing eventually to one of these opportunistic invaders or to certain forms of cancer to which they are also especially susceptible. At the beginning of the epidemic, AIDS was especially prevalent among socially stigmatized members of society–homosexual men and users of intravenous drugs. A decade into the epidemic, the disease is slowly moving into a new subpopulation–inner-city minorities who also live on the margins of mainstream America. Many observers have attributed the slowness of the initial federal

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH response to AIDS to the fact that it appeared to be a sexually transmitted disease confined to these socially marginal subpopulations. The marginality of these groups has also affected other aspects of the nation's response. Because many of those currently infected are among the poorest in the nation, with limited access to primary health care, clinical trials to assess drug efficacy are enormously complicated. These circumstances, and the basic unpredictability of the disease's future course, make the AIDS epidemic a challenge of unprecedented magnitude and complexity for both NIH and the nation. The committee's concerns about the inability of the health care delivery and financing system to respond adequately to the epidemic, and its effects on NIH's capacity to conduct research, are addressed later in this chapter. In the midst of such concerns, however, it is wise to remember that some positive notes have been sounded as well. As the disease has become better understood, behavioral changes among some of the groups most at risk have slowed the advance of infection. In addition, new forms of therapy for those affected have begun to alter the course of the disease, making it more of a chronic than an acute condition. Yet these promising changes are making only modest inroads toward changing the epidemic's course. It is clear that initially afflicted groups are still represented among new cases and that the epidemic is spreading into hitherto untouched populations. NIH'S RESPONSE TO THE EMERGING EPIDEMIC In response to the epidemic, NIH has developed an extensive program of AIDS research that involves every institute at the agency and every type of activity traditionally supported by NIH, ranging from basic research to clinical trials to public information campaigns. In fact, the AIDS program constitutes an unprecedented attempt to address a disease with an NIH-wide program rather than through a single institute. If all AIDS research funds at NIH were allocated to a single institute, it would be the third largest in terms of budget and staff. NIH's role in responding to the emerging epidemic was, and continues to be, only one element of the federal government's AIDS activities. CDC, another PHS agency and the government's lead agency for investigating disease outbreaks, carried out a significant part of the government 's early efforts. In 1981 and 1982, CDC officials investigated case reports of Pneumocystis carinii pneumonia (PCP) and Kaposi's sarcoma, two of the diseases now known to be characteristic of AIDS, and the results of those investigations prompted the initiation of epidemiological studies. In contrast to the CDC focus, NIH launched studies probing the biological basis of the disease, began admitting patients to its clinical center, and began developing requests for grant applications to investigate clinical and scientific aspects of AIDS. Since AIDS was first identified, CDC, like NIH, has greatly expanded its HIV/AIDS program and continues to make significant contributions to controlling the epidemic by its surveillance and education initiatives. The other PHS agencies have also become involved. ADAMHA, through its three institutes (the National Institute of Mental Health [NIMH], the National Institute on Drug Abuse [NIDA], and the National Institute of Alcohol Abuse and Alcoholism [NIAAA]), supports a substantial amount of research on HIV infection. NIMH supports research on neuroscience, neuropsychiatric, and behavioral aspects of HIV infection and AIDS; NIDA and NIAAA focus on the connection between drug use and HIV infection, development of more effective pharmacologic agents to treat drug addiction (increasingly a risk factor for HIV infection), and development of effective behavioral interventions to prevent or stop drug abuse.

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH FDA has regulatory responsibility for ensuring the safety and effectiveness of therapeutic agents, vaccines, diagnostic reagents/test kits, blood and blood products, and medical devices related to HIV infection, AIDS, and associated infections. Another PHS agency, the Health Resources and Services Administration (HRSA), supports several service delivery and education programs, including adult and pediatric service delivery demonstrations, regional AIDS education and training centers, an AZT reimbursement program, and AIDS services in community migrant health centers. The Agency for Health Care Policy and Research (formerly the National Center for Health Services Research) gathers and analyzes data on the costs, quality, delivery, availability, and financing of HIV-related services for different risk groups, geographic locations, stages of illness, treatment modalities, and treatment settings. The Indian Health Service (IHS) supports reservation-based prevention programs, HIV testing and counseling through IHS facilities, and monitoring and surveillance in coordination with the CDC and state health officials. The National AIDS Program Office (NAPO), in the Office of the Assistant Secretary for Health, coordinates PHS activities related to HIV infection and AIDS; it also provides leadership in developing PHS policy related to the epidemic, reviews PHS agency budget requirements, and sponsors a wide range of conferences and forums on AIDS issues. The structure of the NIH AIDS research program evolved incrementally as the agency responded to emerging scientific opportunities, and it reflects NIH's role as a biomedical research agency. In the early years of the epidemic, individual intramural scientists and extramural investigators became involved in AIDS research because they were motivated by the scientific challenges of AIDS; an organized response by NIH did not occur, however, until 1985 when the NIH Director' s Office initiated expedited procedures and coordinating activities for AIDS-related research. Several factors impeded NIH from moving quickly during the epidemic 's first few years. Initially, there was uncertainty about where to look for the causes of AIDS until CDC-sponsored epidemiological studies determined in late 1982 that it was most likely an infectious virus. Moreover, the Reagan administration would not allow NIH to request increased funding for AIDS research for several years, during which time the agency had to reprogram resources from ongoing programs. NIH was also hampered by its own standard operating procedures and decentralized organizational structure, which were oriented toward support of long-range basic research rather than swift, coordinated action on a complicated disease that cut across the traditional missions of the 14 major NIH research units that existed in 1981–1982. (That number has grown to 18 with the addition of the arthritis and deafness institutes and the centers for nursing research and human genome research.) By 1985 NIH had deemed its standard practice of waiting for investigators to submit high-quality proposals too slow for the exigencies of the AIDS epidemic. Under substantial congressional pressure to expand AIDS research, NIH quickly increased its intramural efforts. Extra-murally, it expedited grant reviews, used RFAs and contracts to stimulate research in specific areas, funded some applications with relatively low peer-review scores, and employed cooperative agreements and contracts. To manage and coordinate the interdisciplinary, interinstitute program that had begun to evolve, NIH developed a special administrative system for AIDS activities. The NIH AIDS executive committee was established in 1984 (superseding several working groups created in 1982 and 1983); its membership consisted of representatives from each institute, center, and division involved in AIDS efforts. In 1985 NIH designated NIAID the lead institute and named the NIAID

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH director the NIH AIDS coordinator. It also established the AIDS Program Advisory Committee of outside experts in 1987 to advise the director on AIDS issues. In 1988 NIH created the Office of AIDS Research, located in the Office of the Director, to coordinate intramural and extramural AIDS research, centralize AIDS-related policy and operating functions, and represent the director on matters related to AIDS. At the same time, the NIAID director became associate director for AIDS research throughout the agency. The committee concludes that NIH faced an unprecedented challenge in responding to the epidemic of HIV infection and AIDS, the first pandemic of a new deadly infectious disease to occur in the era of modern biology. Once the magnitude of the epidemic became clear– especially once HIV was identified as the causal agent–NIH was given the mandate and resources to develop a large, multifaceted AIDS research program to understand HIV's pathogenesis, discover and test therapies, and develop prevention strategies and a vaccine. AIDS research supported and conducted by NIH has led to rapid increases in basic knowledge about several aspects of the disease: HIV and its replication, the molecular and behavioral aspects of transmission, the human immune response to HIV infection, and the clinical course of AIDS. Recent projections indicate that the epidemic is still growing and spreading and that its scientific challenges may be changing. Initial scientific inquiries focused on the discovery of the etiologic agent and on understanding the natural history and epidemiology of HIV infection. Once HIV had been identified, however, new scientific opportunities abounded and continue to arise. The major research challenges now are to develop methods to slow and halt transmission of the virus and improve the effectiveness of therapies for those infected. The most promising approaches to controlling transmission are through behavioral change and development of a vaccine. The challenges in developing better therapies focus on the development of pharmacological agents for HIV and for prevention and control of opportunistic infections. Another substantial challenge is the development of more effective ways of providing care for infected individuals. To achieve these goals, much must be learned about the virus itself and its effect on its human host. Major scientific questions remain to be answered in many fields, including immunology, virology, biochemistry, epidemiology, and behavior. Some partially effective therapies have been discovered and developed, and recent advances in vaccine research have convinced many scientists that an effective vaccine may someday be available. Meanwhile, however, the epidemic continues to grow and spread into new areas and populations. HIV infection is a lethal infectious disease that warrants a well-planned, well-organized long-term research program leading to the control and eventual eradication of the disease. The committee concludes that NIH should continue to give AIDS research high priority because HIV infection and AIDS constitute a major public health threat and because they provide substantial opportunities for greater scientific understanding of the human immune system and of other viral diseases that affect mankind. The size and long-term nature of the threat call for an institutionalized response. Recommendation 1.1: NIH should complete its building of the AIDS research program as a comprehensive, long-term effort. The shaping and implementation of such a program will require a series of steps that are described in the remainder of this report.

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH These steps should have several positive results: strengthened management structures and processes for planning, coordinating, evaluating, and reallocating AIDS research activities supported by the various research components of NIH and for ensuring their quality and cost-effectiveness; fuller development of some promising research areas; an increased overall level of support for AIDS research; and increased personnel and facilities resources to enable NIH to conduct and manage an effective, efficient AIDS research program. DEMOGRAPHICS AND PROJECTIONS OF THE EPIDEMIC AIDS was first recognized as a syndrome in 1981 (CDC, 1981; Gottleib et al., 1981), and HIV was identified as the etiologic agent in 1983 (Barre-Sinoussi et al., 1983; Gallo et al., 1984). The World Health Organization (WHO) estimates currently that 8 to 10 million people worldwide are infected with HIV (WHO, 1990a) and that more than 283,000 persons have developed AIDS (WHO, 1990b). WHO also predicts that, by the year 2000, 15 to 20 million persons will have been infected with HIV and that approximately nine times as many adults will develop AIDS during the 1990s as during the 1980s. HIV is transmitted through sexual contact, infected blood or blood products, contaminated needles or syringes, and transplanted tissue or organs from an infected donor, as well as from mother to fetus. HIV is a retrovirus that inserts its genetic material into various types of human cells, which then produce copies of the virus. It invades and eventually destroys T4 lymphocytes, white blood cells that are part of the body's immune system. As infected persons' T4 cells are depleted, they develop AIDS; that is, they develop clinical symptoms and usually die from one of a number of opportunistic infections or cancers that are able to establish themselves because of the body's weakened immune system. The epidemic of HIV infection and AIDS is still growing and has been steadily rising in the national rankings of causes of death. In 1989 the PHS estimated that between 800,000 and 1.2 million persons were infected with HIV in the United States and that although projections indicate that the overall rate of increase has slowed, the incidence of HIV infection is still increasing (CDC, 1990a). As of August 31, 1990, reported AIDS cases totaled 146,746 (CDC, 1990b:Table 1), and CDC estimated that between 390,000 and 480,000 new cases of AIDS would be reported between 1989 and 1993 (CDC, 1990a:Table 2). Also as of the end of August 1990, deaths in the United States from AIDS totaled 89,761 (CDC, 1990b:Table 8). As the annual deaths from AIDS increased from 6,540 in 1985 to 15,026 in 1987, its ranking among causes of death for adults moved from 19th to 15th (National Center for Health Statistics, 1990b:Table 24). The disease will continue to move up in the rankings as the annual number of deaths from AIDS increases from about 32,000 in 1989 to between 53,000 and 76,000 in 1993 (CDC, 1990a:Table 2; Figure 1.11). AIDS' impact ranks higher in terms of years of potential life lost (YPLL) before age 65 because HIV infection and AIDS disproportionately affect the younger segments of the population. More than two-thirds of AIDS patients are less than 40 years of age at the time of diagnosis. In 1988 AIDS ranked sixth in YPLL before age 65 (CDC, 1989b). If actual deaths from AIDS reach 1   Tables and figures appear at the end of the text of each chapter.

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH CDCs midrange estimates, the YPLL before age 65 could reach fifth place in 1991 and third place in 1993 (Table 1.1). The composition of the AIDS population is changing both by geographic area and risk group. Although AIDS is still most prevalent among homosexual and bisexual men and in large metropolitan areas, the epidemic is spreading rapidly among users of intravenous drugs and their sexual partners, minority individuals whose behaviors place them at risk, women, and children. The epidemic is also spreading beyond the urban centers where HIV first made an impact and into less populated areas of the country. For example, prior to 1985, well over half of all reported AIDS cases were in the “first wave ” metropolises of New York, San Francisco, Miami, and Newark. More recent data show increased numbers of AIDS cases in the central region of the country. As of 1988 the percentage of total cases for first-wave cities had dropped to 36 percent; new cases in the rest of the United States rose from 22.1 percent to 37.8 percent of all cases. In addition, 15 other standard metropolitan statistical areas (SMSA) increased their representation from 19.3 to 26.2 percent of all cases (CDC, 1989a). Certain minorities are disproportionately represented among AIDS cases, in part because of higher prevalence among certain groups of illicit drug users and subsequent transmission of the virus to their sexual partners and children (Curran et al., 1988). The pattern of distribution of sexually acquired AIDS parallels the distribution of other sexually transmitted diseases, which are also more frequent among black and Hispanic inner-city populations (Holmes et al., 1990). Blacks constitute 12 percent and Hispanics 7 percent of the U.S. population, but they account for 28 and nearly 16 percent, respectively, of all AIDS cases (CDC, 1990b). Age-adjusted death rates (deaths per 100,000 persons in the resident population) for AIDS in 1988 were 25.4 for black males and 8.3 for white males (the overall age-adjusted rate for deaths from AIDS was 5.5 deaths per 100,000). In 1988 the death rate for black women (10.3 per 100,000) was nine times the rate for white women (1.2 per 100,000; Chu et al., 1990). Intravenous (IV) drug users are increasingly represented among reported AIDS cases. Since 1981 the percentage of AIDS cases ascribed to the use of IV drugs has risen from 11 percent in 1981 to 23.2 percent at the end of 1989 (Table 1.2). CDC estimates that more than one-quarter of all AIDS cases are associated with IV drug abuse (PHS, 1988:66). The PHS also estimates that in communities with large illicit-drug-using populations, such as New York City, the prevalence of HIV infection is between 30 and 40 percent among IV drug users aged 15 through 24 (PHS, 1990a:479). According to CDC estimates, there are 1.1 to 1.3 million IV drug users in this country, all of whom are potentially at risk for HIV infection, as are their sexual partners and children (PHS, 1988:66). Women and children are beginning to account for more and more cases of AIDS and HIV infection. Although the number of women with AIDS (13,807 cases reported through August 1990) is relatively small in relation to the total number of cases, the incidence rate among women has been steadily increasing, from 7 percent of reported cases during 1985 to 11 percent during 1989 (3,931 of 35,238 cases reported; PHS, 1990b). Between 1985 and 1988 the death rate from HIV/AIDS for U.S. women between 15 and 44 years of age quadrupled (from 0.6 to 2.5 per 100,000), and by 1987 HIV/AIDS had become one of the 10 leading causes of death for that age group (Chu et al., 1990). CDC estimates that, of the approximately 1 million Americans who are currently infected, about 100,000 are women, most of whom (79 percent) are in their peak childbearing years–between 13 and 39 (U.S. DHHS, 1988:7,13). As a result, HIV disease is also rising rapidly as a leading cause of death among children in the United States. As of September 1990, CDC reported 2,525 diagnosed cases of AIDS among children and 1,328 deaths (CDC, 1990b). By 1987 AIDS was the ninth leading cause of death among children 1 to 4 years of age

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH and the seventh for young people between the ages of 15 and 24; it is expected to be one of the top five leading causes of death among children by 1990 or 1991 (U.S. DHHS, 1988:7). Approximately 83 percent of all AIDS cases in children under 13 are perinatally acquired (CDC, 1990b:Table 4). Among the AIDS cases in adolescents and young adults aged 13 to 24 reported between 1981 and 1988, the most common mode of transmission among males was homosexual/bi-sexual contact (65.8 percent); the most common mode among females was heterosexual contact (41.6 percent; U.S. DHHS, 1988:Chart 15). HIV infection and AIDS disproportionately affect those who are disenfranchised not only from the health care system but from society as well. All projections indicate that the trends noted above will continue. Therefore, unlike other diseases such as heart disease and cancer, which also pose a significant yet historically stabilized burden of disease, the burden of disease created by the HIV epidemic is still climbing with no end yet in sight. HEALTH CARE FINANCING As noted earlier, the shift in demographics in the HIV/AIDS epidemic also represents a shift toward populations who have poor access to the health care delivery system and thus already carry a disproportionately heavy burden of ill health and disease–to which AIDS is being added. The committee is very concerned that inadequacies in the financing of health care in the United States threaten the research program at NIH, in particular, the conduct of clinical trials for AIDS therapies, as discussed later in this section. Although the state of the nation 's health care delivery system was not within its direct charge, during the course of the study the committee found it impossible not to confront the serious deficits of this system and their deleterious effects on NIH's research efforts. The provision and financing of care for persons with HIV infection are major problems that must be addressed not by NIH but by higher levels of the federal health policymaking establishment. HCFA has estimated that 25 percent of AIDS costs are funded through Medicaid and that 40 percent of all patients with AIDS are served under Medicaid (Winkenwerder et al., 1989:1600). In general, AIDS patients are less likely than the general population to have their health care financed by Medicare or private insurance and more likely to rely on Medicaid or to be uninsured (Figure 1.2). Indeed, recent evidence shows that the proportion of AIDS patients who are covered by private health insurance has declined over time and that payment responsibilities are shifting increasingly to the public sector, primarily to Medicaid (Arno, 1987; Green and Arno, 1990). Several factors account for this trend: (1) the changing demographic face of the epidemic, in which increasing proportions of AIDS cases are occurring among populations (e.g., IV drug abusers, minorities) who are less likely than earlier groups with high incidence (i.e., gay men) to be covered by private insurance and more likely to be covered by Medicaid; (2) the increasing proportion of people with AIDS who have lost their private insurance and have become eligible for Medicaid; and (3) the growing number of private insurers that avoid AIDS cases by selective underwriting of policies (Baily, 1989). Previous Institute of Medicine (IOM)/National Academy of Sciences (NAS) committees (IOM/NAS, 1986, 1988a), an IOM/NAS white paper (IOM/NAS, 1988b), the National Commission on AIDS (1989, 1990), the Congressional Research Service (1989), and health policy researchers (Baily, 1989; Green and Arno, 1990; Makadon et al., 1990; Thorpe, 1990) have all noted that problems with the health care system–particularly the problem of access to care–have especially negative effects on persons with HIV infection. In the United States, health care is financed through a mix of private initiatives and public programs, with most persons gaining access to the

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH medical care system through health insurance (Congressional Research Service, 1988). Approximately 64 percent of the population have employment-related coverage; only about 10 percent rely solely on public coverage (Short et al., 1988). This patchwork arrangement leaves between 31.1 and 37 million Americans with no health insurance (Moyer, 1989). The uninsured are not, however, a representative cross-section of the United States; they are more likely than the insured population to have low incomes, to work part-time or in a small firm, to be under the age of 30, and to be black or Hispanic (Congressional Research Service, 1988). There is, therefore, an overlap between the uninsured population and the groups expected to have increased future incidence of HIV infection (Baily, 1989). The committee believes that facilitating economic and geographic access to health care falls beyond NIH's purview. Agencies and programs outside NIH have the lead responsibility for (1) establishing health care reimbursement policies, (2) financing health care, and (3) providing geographic access to health care. For example, policies established by the Health Care Financing Administration for Medicare and Medicaid affect virtually all elements of the health care system but fall far short of a comprehensive national program for ensuring the delivery and financing of care for poor and minority patients with HIV infection or AIDS. The problem of access to care is beyond the scope of this study. The committee nevertheless concludes that the growing number of AIDS patients, their increasing length of survival after diagnosis, the efficacy of early intervention, and the costs of current and future therapies have implications for the health care system that require urgent attention. The lack of insurance coverage and access to primary health care experienced by many of the populations most at risk for HIV/AIDS seriously impedes NIH's ability to conduct quality clinical research. On one level, it is much more difficult to recruit patients for participation in clinical trials when those patients do not normally receive health care from the hospitals conducting the trials; as a result, certain patient groups are excluded from trials because they lack health insurance or access to a tertiary care center. On a second level, once a patient who lacks health insurance or a primary care provider is recruited for a trial, he or she places great demands on the clinical trials staff for social work services and health care that are often not directly related to the trial protocol. These patients can pose financial burdens either by limiting the overall number of patients a trial site can manage (owing to demands on staff time), or by increasing the level of the hospital's uncompensated care. The NIH clinical research budget of $164 million is only a fraction of what would be needed for comprehensive AIDS care for the more than 60,000 people with AIDS and the estimated 800,000 to 1.2 million persons infected with HIV. The committee believes that NIH's mandate is to facilitate the discovery and clinical evaluation of therapeutic, diagnostic, and preventive agents and not to assure health care. Another serious financial burden facing NIH clinical research centers is the lack of third-party reimbursement for inpatient care for persons participating in clinical trials. Public and private insurers, including Medicare and Medicaid, exclude payment for state-of-the-art care associated with a trial, even when such care is customary and within the normal scope of care that would be provided if the patient were not participating in the trial (Fauci, 1990; McGuire, 1990; Sande, 1990). This practice is based on a traditional policy under which payers do not cover the costs associated with experimental treatments. The issues surrounding third-party reimbursement for necessary and appropriate patient care costs associated with approved clinical trial protocols have been studied by a previous IOM panel, the Committee to Study Resources for Clinical Investigation, and by the National Committee to Review Current Procedures for Approval of New Drugs for Cancer and AIDS (also known as the Lasagna committee). The IOM committee concluded that “it is wholly inappropriate for third-

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH party payers to deny reimbursement for all appropriate and necessary patient care costs (not marginal costs owing to investigational intervention) that would have been incurred in any case simply because a patient is on an investigational protocol” (IOM/NAS, 1988c:7). The committee thus recommended that third-party payers, both governmental and nongovernmental, pay the necessary and appropriate patient care costs for beneficiaries enrolled in approved clinical investigation protocols; they also recommended that the marginal costs related to the clinical investigation be borne by the agency sponsoring the research (IOM/NAS, 1988c:7 –8). The Lasagna committee looked at the approval process for new drugs for life-threatening diseases for which existing therapies are inadequate, including AIDS, and concluded that the medical care costs associated with such research should be covered by Medicare, Medicaid, and private insurers (NCI, 1990:14–15). The Lasagna committee also recommended that investigational drugs, marketed drugs prescribed for unlabeled indications, and ancillary medical care costs be covered by insurers if they were approved by expert government agencies for therapeutic use (such as NCI approval of Group C cancer drugs and FDA approval of drugs under treatment INDs) or included in authoritative medical compendia (such as the three intended for use under the Medicare Catastrophic Coverage Act of 1988; NCI, 1990:13). This committee concurs with these recommendations–that third-party payers should cover the costs of medical care of beneficiaries in approved AIDS clinical trial protocols, costs that would be incurred whether or not the patient were in a clinical trial, and that they should pay for promising investigational drugs for HIV infection and associated infections and cancer. NIH should support the additional costs related to the conduct of the clinical research. Adoption of these recommendations will require a clarification in current Medicare regulations of the definition of medically necessary care. The committee believes these steps are necessary to remove financial barriers to participation in investigational protocols and thus speed advances in AIDS therapeutics. They will also serve to extend and improve the quality of life of those infected by HIV. Recommendation 1.2: The Health Care Financing Administration should make its reimbursement policies consistent with NIH assessments of promising treatments so that when treatments have moved beyond phase 1 testing, their associated medical care costs (and the costs of the treatment if the sponsor is unable to provide it free of charge) are covered for Medicare and Medicaid beneficiaries. Changing HCFA policies to cover treatment and other medical care costs associated with research is only part of the solution to the problem of caring for HIV-infected persons. A more comprehensive approach to financing such care will be needed to eliminate barriers to participation in HIV/AIDS clinical research and to ensure that the improved therapies that emerge from federally supported research are available to those who need them. An earlier IOM/NAS white paper, HIV Infection and AIDS (1988b), based on the work of the IOM/NAS AIDS Activities Oversight Committee, recommended that the Secretary of Health and Human Services “take the lead in developing a comprehensive national plan for delivering and financing care for needy HIV-infected and AIDS patients.” In the meantime, steps should be taken to provide financing for persons who participate in NIH research, either through one of the existing federal health financing programs, such as Medicare or Medicaid, or through a special categorical grant program. Additional actions by NIH to increase participation in clinical research by women, children, minorities, and persons using IV drugs are described in the section on clinical trials in Chapter 3.

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH Recommendation 1.3: The administration and Congress should immediately address and resolve financial barriers to the receipt of appropriate medical care by persons with HIV infection.

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH FIGURE 1.1 Projected annual number of AIDS cases, deaths attributable to AIDS, and living persons with AIDS, United States, 1989–1993. Projections were adjusted by CDC for unreported diagnoses of AIDS by adding 18 percent to projections obtained for reported cases. SOURCE: CDC, 1990a. FIGURE 1.2 Distribution of payers for AIDS and non-AIDS medical care, 1989. SOURCE: Thorpe, 1990:Figure 4.

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH TABLE 1.1 Estimates of Years Potential Life Lost (YPLL) Before Age 65 for HIV/AIDS Year YPLL YPLL Estimate (Lower) YPLL Estimate (Upper) 1987a 363,494     1988a 472,800     1989b 562,602     1989c   848,000 930,000 1990c   1,012,000 1,149,000 1991c   1,176,000 1,423,000 1992c   1,341,000 1,751,000 1993c   1,450,000 2,079,000 NOTE: Footnotes give sources of the mortality data used to compute YPLL estimates. aCDC, 1990c. bNational Center for Health Statistics, 1990a:Table 10. cCDC, 1990a:Table 2. SOURCE: The table was prepared by James W. Buehler, Chief, SpecialProjects Section, Surveillance Branch, Division of HIV/AIDS, Centersfor Disease Control, September 27, 1990.

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH TABLE 1.2 Distribution of Reported Cases (percentage) by Year of Diagnosis and Exposure Category   Adults Pediatric     Year of Diagnosis Male Homo-Bisexual IVDUa Male Homosex. +IVDU Hemo-philiac Hetero-sexual Pattern IIb Transfusion Otherc Hemo-philiac Risky Motherd Transfusion Otherc Total N 1981 64.9 11.0 7.1 0.5 0.5 6.0 0.5 4.5 0.0 4.5 0.0 0.5 100 382 1982 60.7 16.9 9.4 0.6 1.1 5.1 0.8 2.9 0.2 1.7 0.4 0.3 100 1,076 1983 61.4 17.8 9.4 0.5 1.0 3.5 1.5 2.3 0.1 2.0 0.3 0.0 100 2,933 1984 64.3 16.7 8.7 0.9 1.5 2.2 1.7 2.1 0.1 1.5 0.3 0.0 100 5,926 1985 64.1 17.5 7.5 1.0 2.0 1.6 2.5 1.8 0.1 1.5 0.4 0.0 100 11,038 1986 62.9 18.2 7.8 0.9 2.5 1.4 2.7 2.1 0.1 1.3 0.2 0.0 100 17,777 1987 60.5 20.1 6.8 1.0 3.2 1.2 2.9 2.7 0.1 1.3 0.1 0.1 100 25,987 1988 56.9 22.8 6.3 1.0 4.1 1.1 2.5 3.7 0.1 1.3 0.1 0.1 100 29,761 1989e 55.3 23.2 5.8 0.7 5.0 1.2 1.9 5.3 0.1 1.2 0.1 0.1 100 22,901 Total 59.5 20.6 6.9 0.9 3.4 1.4 2.4 3.3 0.1 1.4 0.2 0.1 100 117,781 aIVDU: intravenous drug user. bThe cases assigned to this category involve individuals from those countries in central, eastern, and southern Africa and some Caribbean countries in which the majority of AIDS cases have been ascribed to heterosexual transmission, the male-to-female case ratio is approximately 1:1, perinatal transmission is more common than in other areas, and intravenous drug use and homosexual transmission occur at a very low level. cThis category includes cases currently under investigation for which no history of exposure has yet been reported and cases for which no exposure mode could ever be determined. dMother with, or at risk for, HIV infection. eThe 1989 figures include only those cases reported through December 31, 1989. All data shown in this table are subject to delays in reporting. Therefore, counts of cases diagnosed in a particular year may understate the number that will ultimately be reported. This type of understatement is particularly likely for cases diagnosed in 1988 and 1989. SOURCE: National Research Council, 1990: Table 1.1. Computed from CDC's AIDS Public Information Data Set for AIDS cases reported throughDecember 1989.

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH REFERENCES Arno, P. S. 1987. The economic impact of AIDS. J. Am. Med. Assoc. 258:1377–1397. Baily, M. A. 1989. Private insurance as a source of financing for HIV-related care. Testimony before the National Commission on AIDS, Washington, D.C. November 3. Barre-Sinoussi, F., J. C. Chermann, F. Ray, M. T. Nugeyre, S. Chamaret, J. Gruest, C. Dauget, C. Axler-Blin, F. Vezinet-Brun, C. Rouzioux, W. Rozenbaum, and L. Montagnier. 1983. Isolation of a T-lymphotrophic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–871. CDC (Centers for Disease Control). 1981. Kaposi's sarcoma and Pneumocystis pneumonia among homosexual men–New York City and California. Morbid. Mortal. Wkly. Rep. 30:305–308. CDC. 1989a. AIDS Weekly Surveillance Report, January 20, 1989. Atlanta, Ga.: CDC. CDC. 1989b. Fact Book FY 1989. Atlanta, Ga.: CDC. CDC. 1990a. Estimates of HIV prevalence and projected AIDS cases: Summary of a workshop, October 31–November 1, 1989. Morbid. Mortal. Wkly. Rep. 39:110–119. CDC. 1990b. HIV/AIDS Surveillance, September 1990. Atlanta, Ga.: CDC. CDC. 1990c. Years of potential life lost before ages 65 and 85–United States, 1987 and 1988. Morbid. Mortal. Wkly. Rep. 39:20–22. Chu, S. Y., J. W. Buehler, and R. L. Berkelman. 1990. Impact of the human immunodeficiency virus epidemic on mortality in women of reproductive age, United States. J. Am. Med. Assoc. 264:225–229. Congressional Research Service. 1988. Health Insurance and the Uninsured: Background Data and Analysis. CRS Report No. 88-537 EPW. June 9. Washington, D.C.: Congressional Research Service, Library of Congress. Congressional Research Service. 1989. Acquired Immunodeficiency Syndrome (AIDS): Health Care Financing and Services. Issue Brief 87219. Updated August 16, 1989. Washington, D.C: Congressional Research Service, Library of Congress. Curran, J. W., H. W. Jaffe, A M. Hardy, W. M. Morgan, R. M. Selik, and T. M. Dondero. 1988. Epidemiology of HIV infection and AIDS in the United States. Science 239:610–616. Fauci, A. 1990. Testimony before the Human Resources and Intergovernmental Relations Subcommittee of the Committee on Government Operations, House of Representatives, Congress of the United States. August 1. Gallo, R. C., S. Z. Salahuddin, M. Popovic, G. M. Shearer, M. Kaplan, B. F. Haynes, T. J. Palker, R. Redfield, J. Oleske, B. Safai, G. White, P. Foster, and P. D. Markham. 1984. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science 224:500–503. Gottleib, M. S., R. Schroff, H. M. Schanker, J. D. Weisman, P. T. Phan, R. A Wolf, and A. S. Saxon. 1981. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: Evidence for a new acquired cellular immunodeficiency. N. Engl. J. Med. 305:1425–1431. Green, J., and P. S. Arno. 1990. The “Medicaidization” of AIDS: Trends in the financing of HIV-related medical care. J. Am. Med. Assoc. 264:1261–1266. Holmes, K. K., J. M. Karon, and J. Kreiss. 1990. The increasing frequency of heterosexually acquired AIDS in the United States, 1983–88. Am. J. Public Health 80:858–863. IOM/NAS (Institute of Medicine/National Academy of Sciences). 1986. Confronting AIDS: Directions for Public Health, Health Care, and Research. Washington, D.C.: National Academy Press. IOM/NAS. 1988a. Confronting AIDS: Update 1988. Washington, D.C.: National Academy Press. IOM/NAS. 1988b. HIV Infection and AIDS: Recommendations for President-elect George Bush. Washington, D.C.: National Academy Press. IOM/NAS. 1988c. Resources for Clinical Investigation. Washington, D.C.: National Academy Press. Makadon, H. J., G. R. Seage, K. E. Thorpe, and H. V. Fineberg. 1990. Paying the medical cost of the HIV epidemic: A review of the policy options. JAIDS 3:123–133. McGuire, J. 1990. Testimony before the Human Resources and Intergovernmental Relations Subcommittee of the Committee on Government Operations, House of Representatives, Congress of the United States. August 1. Moyer, M. E. 1989. A revised look at the number of uninsured Americans. Health Affairs 8:102–110. National Center for Health Statistics. 1990a. Annual summary of of births, marriages, divorces, and deaths: United States, 1989. Monthly Vital Statistics Rep. 38:1–30. National Center for Health Statistics. 1990b. Health, United States, 1989. March. DHHS Pub. No. (PHS) 90-1232. Hyattsville, Md.: National Center for Health Statistics. National Commission on Acquired Immune Deficiency Syndrome. 1989. Report Number One. December 5. Washington, D.C.: National Commission on Acquired Immune Deficiency Syndrome. National Commission on Acquired Immune Deficiency Syndrome. 1990. Report Number Three. August 21. Washington, D.C.: National Commission on Acquired Immune Deficiency Syndrome. National Research Council. 1990. Table 1.1 in AIDS: The Second Decade. Washington, D.C.: National Academy Press. NCI (National Cancer Institute). 1990. Final Report of the National Committee to Review Current Procedures for Approval of New Drugs for Cancer and AIDS. August 15. Washington, D.C.: President's Cancer Panel, National Cancer Institute. PHS (Public Health Service). 1988. Report of the Second Public Health Service AIDS Prevention and Control Conference. Public Health Reports 103(Suppl. 1, Rev.).

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THE AIDS RESEARCH PROGRAM OF THE NATIONAL INSTITUTES OF HEALTH PHS. 1990a. Healthy People 2000: National Health Promotion and Disease Prevention Objectives (conference ed.). September. Washington, D.C.: Office of Disease Prevention and Health Promotion. PHS. 1990b. The Role of the Public Health Service in Combatting the HIV/AIDS Epidemic (August 31 Draft). Washington, D.C.: National AIDS Program Office. Sande, M. 1990. Remarks at NIAID Advisory Council meeting. May 21. Short, P. F., A. Monheit, and K. Beauregard. 1988. Uninsured Americans: A 1987 Profile. Rockville, Md.: National Medical Expenditure Survey, National Center for Health Services Research and Health Care Technology Assessment. Thorpe, K. E. 1990. Medicaid Expenditures on AIDS: Future Trends and Policy Issues. Prepared statement for hearings of the House Subcommittee on Health and the Environment, Committee on Energy and Commerce. February 27. Mimeo. U.S. DHHS (U.S. Department of Health and Human Services). 1988. Final Report: Secretary's Work Group on Pediatric Infection and Disease. November 18. NIH Pub. No. 89-3063. Washington, D.C.: Department of Health and Human Services. WHO (World Health Organization). 1990a. Global Programme on AIDS Update: AIDS Cases Reported to the Surveillance, Forecasting and Impact Assessment Unit. September. Geneva, Switzerland: Global Programme on AIDS. WHO. 1990b. WHO Revises Global Estimates of HIV Infection (press release). July 31. Geneva, Switzerland: Global Programme on AIDS. Winkenwerder, W., A. R. Kessler, and R. M. Stolec. 1989. Federal spending for illness caused by the human immunodeficiency virus. N. Engl. J. Med. 320:1598–1603.

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