Statement of
Elias Zerhouni, M.D.
Director, National Institutes of Health

Mr. Chairman and members of the Committee, I am pleased to be here today to provide you with an update on the research activities of the National Institutes of Health (NIH) to address global HIV/AIDS and Severe Acute Respiratory Syndrome (SARS). With the advent of SARS, we once again are reminded of the importance of our mission to develop new and improved treatments, preventions, and diagnostic tools for infectious diseases of significance around the world. Let me also say that our collaborations with the CDC have traditionally been -- and continue to be -- fruitful, and our agencies are working together to address diseases that threaten millions across the globe.

Mr. Chairman, let me present to you Dr. Anthony S. Fauci, the Director of the National Institute of Allergy and Infectious Diseases at NIH, who will testify on behalf of the NIH about our research efforts to combat global HIV/AIDS and SARS.

Statement of
Anthony S. Fauci, M.D.
Director, National Institute of Allergy and Infectious Diseases
National Institutes of Health

Mr. Chairman and members of the Committee, thank you for inviting me here today to discuss two global health threats, HIV/AIDS and Severe Acute Respiratory Syndrome, or SARS. These are just two among many threats we face from emerging and re-emerging infectious diseases-which include the threat of bioterrorism. I will first discuss the international aspects of the NIH research program on HIV/AIDS. I will then outline how NIH has responded to SARS in the six weeks that have passed since this disease was first recognized. I will close with a few thoughts on how the United States can strengthen its ability to react effectively to global emerging or re-emerging disease threats.

Global HIV/AIDS

HIV, the emerging virus that causes AIDS, was identified just 20 years ago. Today, approximately 42 million people worldwide are living with HIV/AIDS. HIV/AIDS is truly a global pandemic with no end in sight. Sub-Saharan Africa is hardest hit, with more than 29 million people infected. South and South-East Asia together account for more than 6 million infected people, with 1.2 million more in Eastern Europe and Central Asia, and 1.9 million in Latin America and the Caribbean. During the past year, approximately 14,000 people worldwide were infected with HIV every day. Over the next seven years, it is projected that approximately 45 million more people will become infected. Without the implementation of effective prevention and treatment measures, it is anticipated that by the year 2020 approximately 70 million people will have died of AIDS.

The global impact of HIV/AIDS demands a global response. The President's overall budget request for AIDS research at NIH for FY 2004 is $2.9 billion, of which $274.7 million will be used for research in countries other than the United States. Of course, the progress NIH makes in the arena of HIV research will benefit the entire world, whether the research is conducted in this country or abroad. However, collaborative research conducted in developing countries seriously afflicted with HIV/AIDS is highly focused on specific health issues that are most critical to the countries in question.

The NIH international HIV/AIDS research portfolio addresses a broad range of HIV-related health issues. NIH currently supports 260 international AIDS research projects in over 80 countries, as well as more than 30 clinical network sites. The NIH international HIV/AIDS research agenda includes the development of vaccines and other prevention strategies, identification of culturally appropriate social and behavioral interventions to stop transmission of HIV, testing of therapeutic approaches for HIV and common co-infections such as tuberculosis and malaria, discovery of new ways to prevent HIV transmission at birth and through breast-feeding, and basic research. All of these international AIDS research projects require the direct involvement of foreign researchers as equal partners in their design, conduct, and analysis. NIH also helps to strengthen research in resource-poor countries by training scientists, clinicians, and health care workers in research techniques, and by enhancing local laboratory, clinical, and data management capabilities. In this regard, in 1999, NIH established two large international networks for clinical HIV research. One of these, the HIV Vaccine Trials Network (HVTN) evaluates vaccines for safety and efficacy, and works to ensure that vaccine candidates are appropriate to the regions where they will be used. This network currently has sites in 13 countries and soon will be expanding. The HIV Prevention Trials Network (HPTN), which currently operates in 14 countries, evaluates the safety and efficacy of other prevention strategies, such as cost-effective drug therapies to reduce mother-to-infant transmission, behavioral interventions to help prevent sexual transmission of HIV, prevention and control of sexually transmitted diseases that increase the probability of HIV transmission, and topical microbicides that provide a chemical barrier to transmission. In addition to these two major international efforts, other NIH-supported clinical HIV research networks also are being expanded internationally, and are working in close collaboration with the HPTN and the HVTN.

As another example of our global outreach, NIAID in 2001 launched an innovative program called the Comprehensive International Program of Research on AIDS (CIPRA) to help investigators in developing countries carry out comprehensive, long-term HIV/AIDS research tailored to the needs of the local population. In order to be eligible, researchers must conduct the work in a country with a per capita income less than $5,000. CIPRA is specifically structured to allow applicants to build comprehensive, multidisciplinary projects from the ground up. The program initially helps these scientists to plan a research program, establish collaborations, and build administrative and research infrastructure. As their research capacity grows, they can seek additional CIPRA funding. CIPRA now has three multidisciplinary research projects - one in Beijing, China, and two in South Africa. Planning and organizational grants have been awarded in Trinidad and Tobago, Peru, Zambia, Russia, and Vietnam, among other countries.

The single most important tool that is needed to fight this epidemic is an effective vaccine. One of the most serious obstacles that vaccine developers face is the ability of HIV to rapidly mutate, which leads to a great deal of heterogeneity in the virus. Thus, a vaccine that might work in a part of the world where one form of the virus predominates would not necessarily work in another region. NIAID recently has developed a candidate HIV vaccine that addresses this problem directly. The candidate is designed to induce antibodies that can bind to proteins from the three most prevalent HIV subtypes, or "clades." It is hoped that this new vaccine candidate will provide broad protection against all three of these subtypes, which together are responsible for approximately 90 percent of HIV infections worldwide. A pilot safety trial of this vaccine already is under way, and expanded tests conducted through NIAID's HVTN are planned for several U.S. sites, as well as sites in Haiti and South Africa. Many other vaccine candidates are in various stages of clinical development.

In addition to vaccines, we are pursuing many other strategies to prevent HIV transmission. Some of these have begun to produce results. For example, a pivotal NIH-supported study conducted in Uganda demonstrated that a single dose of the drug nevirapine given to an HIV-infected woman at the onset of labor, combined with a single dose for the infant just after birth, was 50 percent more effective in preventing transmission to the baby than was a short course of the drug AZT. Research is now underway to determine if the use of nevirapine or other drugs can prevent transmission through breastfeeding, a major mode of mother-to-infant transmission. Other HIV prevention strategies include development of effective chemical and physical barrier methods, research on the use of these methods among different populations, and a study of how antiretroviral therapy might prevent transmission by reducing how much virus a patient sheds in their genital track or in breast milk.

In the United States and other western countries, potent combinations of anti-HIV drugs (highly active antiretroviral therapy, or "HAART") have dramatically reduced the numbers of new AIDS cases and deaths due to HIV/AIDS. Meanwhile, the toll of AIDS has accelerated elsewhere in the world, especially in poor countries where expensive HAART regimens are beyond the reach of all but a privileged few. Fortunately, this disparity in access to life-saving medications may be changing. Building on the research infrastructure that NIH has helped establish in Africa and elsewhere in the developing world, we are actively working with our international colleagues to link the provision of anti-HIV therapies to efforts in prevention research, with the goal of facilitating a comprehensive approach to the AIDS pandemic in poor countries. Implementation of this strategy will be considerably enhanced by the recently announced President's Emergency Plan for AIDS Relief, which will create an opportunity for us to address important operational research questions within the context of the treatment, prevention and care components of the President's Plan.

The President's Plan complements ands calls for significant contributions to the Global Fund to Fight AIDS, Tuberculosis and Malaria, whose board is chaired by HHS Secretary Tommy Thompson. The United States was instrumental in the establishment of the Global Fund, was the first country to make a contribution, and leads the world in funds pledged to date.

The development of research infrastructure in the resource-poor countries with whom we collaborate is critical to the NIH mission in NIH international HIV/AIDS research. Specific international needs include the establishment of representative and stable groups of volunteers for safety and efficacy studies, as well as increasing the number of workers trained in basic, clinical and behavioral research, data management, and clinical bioethics. NIH international programs, such as the Fogarty International Center's AIDS International Training and Research Program, provide traineeships at U.S. academic and medical schools. In-country training also is provided in many host nations through these programs. A new initiative recently was launched to provide foreign researchers who have been trained in the U.S. with pilot funds upon their return to their own country in order to ensure their continued capability to conduct AIDS research and continue collaborations with their U.S. counterparts. Another new initiative is the targeting of training in the area of clinical operational health services research on AIDS and tuberculosis. All of these examples underscore our belief that the best way to meet the global pandemic of HIV/AIDS is through global outreach and collaboration.

SARS

The world currently is facing a new, evolving and potentially very serious infectious disease threat -- the Severe Acute Respiratory Syndrome or SARS. Only six weeks have passed since SARS was first recognized but it already has become a worldwide health emergency, with quarantines, travel disruptions, widespread fear, and the threat of serious economic damage. As of April 5, 2003, the World Health Organization (WHO) had reported more than 2,400 SARS cases in 18 countries, including 89 deaths. In the United States, 115 suspected cases in 28 states had been reported to the Centers for Disease Control and Prevention (CDC) as of that date. Since the epidemic is still evolving, it is impossible at this time to predict its ultimate outcome this year or its potential in future years. However, an effective response to this threat must involve both public heath measures and biomedical research.

As a result of the work of the CDC and WHO, as well as NIH and other organizations around the world, scientific progress on SARS has been swift and impressive. Research led by CDC strongly implicates as the cause of SARS a new coronavirus that may have recently crossed species from an animal to humans. The suspect virus has been grown in the laboratory in cell culture, its genetic sequence has been determined, and that sequence has been used to help develop a specific diagnostic test.

NIAID is the NIH institute with primary responsibility for research on emerging infectious diseases. In the short time since SARS came to the attention of the world, NIAID has made significant contributions by mobilizing the same talents, strategic processes, and knowledge base used in NIAID biodefense efforts. It is clear that naturally emerging infectious diseases can be no less a threat to global health than the deliberately released microbes of a bioterror attack. NIAID efforts related to SARS include the following:

Surveillance and epidemiology. NIAID supports a research team in Hong Kong dedicated to the surveillance of emerging infectious, especially influenza viruses. This group also has identified a coronavirus in association with SARS and has been complementary to the CDC's efforts. In addition, at the request of WHO, NIAID assigned a staff epidemiologist to provide epidemiological and logistical assistance in Geneva during the early stages of the SARS epidemic.

Vaccine Research. NIAID's intramural research laboratories, including the Vaccine Research Center, are already working to develop a vaccine to prevent the disease. Of note, researchers in the NIAID Laboratory of Infectious Diseases are now actively growing the SARS coronavirus in tissue culture for the purpose of developing a vaccine. Furthermore, NIAID is collaborating with CDC, FDA, the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), and other agencies to develop strategies for SARS coronavirus vaccine development. NIAID also is consulting with companies and other organizations that have reagents, cell lines, animal models, and other technologies relevant to vaccine development.

Therapeutics Research. NIAID responded rapidly to a request from CDC to evaluate candidate antiviral therapeutic agents through a collaborative antiviral drug-screening project at USAMRIID. NIAID also has initiated discussions with pharmaceutical companies on candidate antiviral drugs, and is reviewing a proposal for a clinical trial of antiviral therapy to be conducted by members of the Institute's Collaborative Antiviral Study Group and the NIH Clinical Center. Furthermore, NIAID-supported researchers at Utah State University will evaluate the efficacy of existing antiviral drugs against SARS using a cell-culture system and similar coronaviruses that infect the human respiratory tract, but do not cause disease.

Clinical Research. In collaboration with the CDC, NIAID is prepared to accept patients with SARS for evaluation and treatment at the NIH Clinical Center. Moreover, NIAID-funded extramural research laboratories, such as the Respiratory Pathogens Research Unit at the Baylor College of Medicine in Houston, have molecular and cell-based diagnostic tests for known coronaviruses. The already planned expansion of these laboratories in 2003 will increase our capacity to address emerging acute viral diseases, such as SARS. NIAID also will support clinical trials of candidate vaccines and drugs that are active against coronaviruses as they become available.

Basic Research. NIAID has a long-standing interest and involvement in basic research on coronaviruses (see above) and currently funds 18 projects in this area; we plan to expand this effort in response to the recent outbreak. Also, the study of SARS patients, as well as patient laboratory specimens in NIAID laboratories, will be important in illuminating the natural history of the SARS agent, its potential animal reservoir, its pathogenic mechanisms and its basic biology. These studies will in turn help to identify targets for antiviral drugs, diagnostic tests, and vaccines.

Other Activities. NIAID, together with the NIH Clinical Center staff, are collaborating with CDC on technical approaches to confirming the identity of the new virus, as well as the clinical management and care of SARS patients.

Building Response Capability

SARS is only the latest in a long series of emerging and re-emerging infectious diseases to confront us. We can be quite certain it will not be the last. In order to meet these challenges successfully in the future, we need a vigorous research program in infectious diseases supported by a robust national research infrastructure-including strong scientific expertise. Because basic research findings contribute to the development of better tools to identify and interdict microbial threats, we need our research program to be well integrated with public health surveillance and response systems. In order to accomplish these ends, NIAID works constantly to strengthen our basic and applied research programs on the many host, pathogen, and environmental factors that influence disease emergence, while supporting the development of diagnostics, vaccines, and therapies necessary to detect and control diseases as they appear.

It is important to make two specific points concerning how we are strengthening our ability to respond to emerging infectious disease threats. First, these threats are global, and modern air travel has effectively made the world considerably smaller than it once was. It is therefore essential that we work collaboratively with scientists in other countries, particularly in developing countries where the burden of emerging infectious diseases has an extraordinary impact. NIAID funds research on emerging and global infectious disease threats in 120 countries around the world, and works through the NIH Fogarty International Center to carry out training and research programs to enhance the skills of scientists in developing countries. NIH's support for this kind of international effort is a productive investment that will greatly improve our chances of meeting emerging threats quickly.

Second, to carry out our research agenda we must have adequate research resources, including research laboratory capacity. Accordingly, Congress has appropriated approximately $834 million over the past two years to help address these needs. Research on many diseases must be conducted in specialized containment facilities to obviate the threat to laboratory personnel and nearby communities, and to allow work with animal models and clinical research. NIAID has established a comprehensive plan for building the needed facilities. This plan calls for a national network consisting of several Regional Centers of Excellence for Biodefense and Emerging Diseases Research, one to two National Biocontainment Laboratories with BSL-4 capability, and a number of Regional Biocontainment Laboratories, rated at the BSL-3 level. In his January 7th Budget Amendment in FY 2003, the President proposed that funding for these extramural biosafety labs be accelerated from FY 2004 to FY 2003. In its FY 2003 appropriation action, the Congress concurred, providing $372 million for this purpose.

NIAID also plans to expand BSL-3 and BSL-4 capacity within its own facilities, both on the NIH campus in Bethesda and at the Rocky Mountain Laboratory facility in Montana. Together, these facilities will provide state-of-the-art laboratory space to support biodefense and emerging disease research, and will allow for a greater "surge" research capacity in the event of a threat.

Conclusion

After the emergence of SARS, HIV/AIDS, West Nile Virus, drug resistant bacteria and other infectious disease threats -- including bioterrorism -- it is clear that emerging or re-emerging infectious diseases pose serious threats to global public health and security. At NIAID, we accept the challenges that countering these threats pose, and are committed to basic and applied research to strengthen the nation's ability to cope with both known infectious diseases and those that will inevitably emerge in the future.

Thank you for the opportunity to testify. I would be happy to answer any questions you may have.