Sustaining the Investment in AIDS Research

By any criteria, AIDS must be considered the great plague of the 20th century. The epidemic's spread around the globe has been rapid. The disease has already caused more than 11.7 million deaths worldwide since its appearance in the late 1970s. With an estimated 30.6 million current infections, and new infections occurring at the rate of more than 250,000 monthly, the potential magnitude of the HIV/AIDS pandemic is truly profound. In response, the National Institutes of Health (NIH) has developed a comprehensive biomedical and behavioral research program to better understand the basic biology of HIV, develop effective therapies to treat it, and design interventions to prevent transmission. For FY 1999, the U.S. Congress appropriated $1.8 billion to the NIH for the AIDS research program, which will ensure continued progress in these areas. A dramatic development in AIDS research and care during the past two years has been the introduction of highly active antiretroviral therapy (HAART), combinations of drugs that include protease inhibitors. For many HIV-infected individuals, these treatment regimens have reduced viral burdens to undetectable levels, arrested the progression to AIDS, and significantly reduced AIDS-related death rates in the United States and other industrialized nations. But this remarkable success has also been misinterpreted by some observers to mean that we have turned the corner on this epidemic and, therefore, that the need is less urgent for a strong, sustained investment in AIDS research. The commitment to AIDS funding also has been challenged by a number of disease-oriented groups, some of whom suggest that the determination of research funding should be based on a "dollars-per-death" ratio; the implication is that AIDS research is disproportionately well funded compared to research in heart disease, cancer, and other diseases that account for greater overall mortality in the United States. In this brief piece, I will highlight just a few of the reasons why it is essential to sustain and increase the investment in AIDS research until effective ways are found for preventing and treating this disease on a global scale, and why comparisons to other diseases are inappropriate. There are three critical and related reasons to continue and expand our AIDS research investment: need, the multiplier effect, and scientific opportunity. While the overall death rate due to AIDS has declined in the United States, HIV incidence rates have not changed. Moreover, new HIV infections and AIDS-related deaths continue to increase dramatically in many subpopulations, particularly women and minorities. Throughout the developing world, including sub-Saharan Africa, the Indian subcontinent, and southeast Asia, the epidemic continues to rage. New epidemics are emerging and rates of HIV and AIDS increasing in some parts of the world, such as Eastern Europe and China (see story, page 1). The need to address continuing HIV incidence is salient. In the United States (as here), the epidemic actually consists of many sub-epidemics. AIDS continues to affect those most disenfranchised in our society--the poor, the homeless, and those with addictive or mental disorders. AIDS cases are rising among women, racial/ethnic minorities, heterosexuals, adolescents, drug users, and people over 50 years of age. AIDS remains a leading cause of death among all Americans 18 to 44 years old, and the leading cause of death among African American males 25 to 44 years old. The U.S. HIV/AIDS epidemic is not isolated. The transmissibility of HIV--between individuals and across borders and populations--is what most defines the global pandemic and makes it imperative that the United States help address prevention and treatment needs worldwide. The transmissible nature of HIV also makes it radically different from nontransmissible diseases such as heart disease and cancer. Because HIV is an infectious disease, any intervention that reduces the probability of transmission--breaking a link in the epidemic chain--has an effect that extends far beyond the treated or protected individual to an infinite series of potential infections that are averted. Preventing one infection is therefore preventing the potential for many other infections. The possibility for dramatic reductions in new infections--and ultimate control of the pandemic--exists for HIV/AIDS in a way that will never be possible for noninfectious diseases. This possibility is illustrated in the graph published here, which compares two infectious diseases--tuberculosis and poliomyelitis--with heart disease and cancer. It is clear that the annual death rate for cancer and heart disease did not change dramatically from 1950 to 1990 in spite of a long-term research investment that has produced marked advances in prevention, early diagnosis, and therapy. In contrast, tuberculosis deaths declined during the same period as a result of reduced transmission due to improved living conditions and the introduction of effective treatments. Polio, another infectious disease, was brought under control--and has been eliminated in 145 countries--by preventive vaccines. An intensive investment in biomedical and behavioral AIDS research could have the same dramatic effect on HIV infection and AIDS. Investment in HIV/AIDS research to date has yielded a rich lode of knowledge, materials, and methods that have set the stage for a wide variety of new advances and interventions to benefit HIV-infected individuals, those at risk of infection, and, in fact, those who suffer from a number of other life-threatening illnesses. Treatment. Groundbreaking research in basic biology has led to a revolution in drug design and diagnostic methodologies that are benefiting the fight not only against AIDS, but also against other diseases. In the case of AIDS, this basic research has been the foundation for the development of medications that are extending the quantity and quality of life for many HIV-infected individuals. Nevertheless, a number of problems remain. Chief among these is that even when viral burden is greatly reduced, the virus has not been completely eliminated from the body and may still be transmissible. Other treatment issues requiring further research include: long-term benefits of HAART; immune function restoration; drug side effects; development of drug resistance; adherence to complex medical regimens; and differential access to life-extending therapies. Prevention. Important advances have also been made in diagnosis and prevention of perinatal HIV infection. A NIH-funded clinical trial (ACTG 076) showed that therapeutic intervention protocols can reduce perinatal transmission by approximately 70 percent in countries where AZT is affordable.1 In addition, a recent trial of a modified, much less expensive protocol for potential use in developing countries demonstrated the ability to reduce transmission by 50 percent.2 To reduce transmission further, additional research is necessary, including studies to better understand the timing, mechanisms, and risk factors of perinatal transmission; whether specific strains are more likely transmitted; the potential benefit of Cesarean section; and development of newer therapeutic regimens and immunotherapy. The virtual elimination of perinatal transmission in our nation and the world is a goal that must be vigorously pursued. Heterosexual transmission has been the chief route of HIV infection in most of the world and accounts for an increasing proportion of new infections in the United States, particularly among women and racial/ethnic minorities. It is critical to develop new interventions that will have the greatest impact on these groups--for example, effective and acceptable female-controlled methods to block transmission of HIV, such as microbicides. We also are in great need of interventions that address the co-occurrence of HIV and other STDs, hepatitis, drug abuse, and mental illness, and that account for the role of culture, family, and other social factors in the transmission and prevention of these disorders, especially in minority communities. While the AIDS epidemic in the United States has stabilized among white gay men overall, it is increasing among younger men who have sex with men, including men of color. It is crucial to develop interventions to address the specific behavioral and psychosocial risk factors prevalent among communities of young gay men. Drug users and their sex partners are the fastest growing segment of AIDS cases in this and many other countries. High priority must be given to research to understand the phenomenon of addiction itself, as well as the complex interaction of alcohol, drug use, and poor impulse control. Scientifically based interventions have been demonstrated to alter sexual and drug-using behavior and reduce the risk of transmission among a number of population groups. But we are still far from realizing the full potential of such prevention research on a global scale. Neal Nathanson is Director of the Office of AIDS Research at the National Institutes of Health and Emeritus Professor of Microbiology at the University of Pennsylvania. This commentary reflects the contributions of Judy Auerbach, Fulvia Veronese, Wendy Wertheimer, and Jack Whitescarver of the Office of AIDS Research. Vaccines. The remarkable advances in HIV therapies and behavioral interventions notwithstanding, it is generally believed that true, global control of the AIDS pandemic will require a safe and effective vaccine. Development of an AIDS vaccine presents a daunting scientific challenge, much more difficult than the formulation of effective vaccines for acute viral diseases such as measles, poliomyelitis, and smallpox. It is important to acknowledge that even when an effective AIDS vaccine is developed and delivered to people around the world, it will always be imperative to employ it with other approaches to prevention and treatment, if we are ever to control HIV/AIDS in the long run. The continuing incursion of HIV infection and AIDS in populations and communities throughout the United States and the world, the uniqueness of HIV/AIDS as an infectious, debilitating disease, and the opportunity for ongoing advances in science to more effectively address the pandemic means that an intensive, sustained commitment to HIV/AIDS research now and in the foreseeable future is required. E.M. Connor et al., "Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment," New England Journal of Medicine, 331:1173-80, 1994; see also Hot Papers comments by E.M. Connor, The Scientist, 10[16]:15, Aug. 19, 1996. S. Taneepanichskul et al., "Effect of zidovudine treatment in late pregnancy on HIV-1 in utero transmission," Australian & New Zealand Journal of Obstetrics & Gynaecology, 37:329-31,1997.

Sustaining the Investment in AIDS Research

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