Mr. Chairman and Members of the Committee, I am pleased to appear before you today to discuss the human immunodeficiency virus (HIV) epidemic, recent developments in HIV research, and the many challenges that remain in the fight against HIV and the acquired immunodeficiency syndrome (AIDS).

The Scope of the Epidemic

AIDS was recognized eighteen years ago this summer, and continues to exact an enormous toll throughout the world, in both human and economic terms. In the United States, the rate of new HIV infections—approximately 40,000 per year—remains unacceptably high, despite an encouraging downturn in new AIDS cases and AIDS-related deaths.

In the developing world, the HIV/AIDS epidemic continues to accelerate, notably in sub-Saharan Africa, southeast Asia and on the Indian sub-continent. There are also signs of expanding epidemics in Russia and other New Independent States of the former Soviet Union. As of the end of 1998, more than 33 million people worldwide were living with HIV/AIDS, according to estimates by the Joint United Nations Programme on HIV/AIDS (UNAIDS). An estimated 5.8 million new HIV infections occurred worldwide during 1998—approximately 16,000 new infections each day. More than 95 percent of these new infections occurred in developing countries. Alarmingly, in 27 developing countries, HIV prevalence more than doubled between 1995 and 1997. In 1998, HIV/AIDS was the fourth leading cause of mortality worldwide, resulting in an estimated 2.3 million deaths.

Beyond the human tragedy of HIV/AIDS, the economic costs of the epidemic are staggering, posing a significant impediment to the growth and stability of many countries where the epidemic is decimating a limited pool of skilled workers and managers as well as young people at the peak of their productive years. According to UNAIDS, life expectancy in the nine countries in Africa with the highest HIV prevalence rates will, for the first time in many years, decline an average of 17 years by 2015 due to HIV/AIDS.

Clearly, HIV remains one of the greatest threats to global health, and requires a sustained commitment by the various partners in AIDS research and prevention: U.S. and foreign government agencies, UNAIDS, non-governmental and philanthropic organizations, academia, industry, and the activist community. This week Vice President Gore reinforced the Administration's commitment to combating AIDS worldwide by announcing a proposal to spend an additional $100 million in FY 2000 on prevention and treatment strategies, community-based care and assistance for children orphaned by AIDS.

Today, I will focus on NIH’s role in the development of treatment and prevention strategies for HIV/AIDS.

Antiretroviral Therapies

As noted above, new AIDS diagnoses and deaths have dropped significantly in the United States in the past two years, and the same is true in other developed countries. These trends are probably due to several factors, particularly the increased use of potent, albeit expensive, combinations of HIV drugs. Sixteen antiretroviral drugs are now licensed in the United States, and several new agents are in various stages of clinical testing. Consensus guidelines have been developed for the use of anti-HIV medications that, when appropriately applied, have greatly improved the prognosis for HIV-infected individuals.

Unfortunately, many HIV-infected individuals have not responded adequately to the medications, cannot tolerate their toxicities, or have difficulty adhering to complex dosing schedules and substantial pill burdens. In addition, the ability of HIV to mutate and become resistant to the current drugs is a persistent threat. Although there is evidence of immune system reconstitution in certain patients who receive combination antiretroviral therapy, the goals of completely "rebuilding" the immune system or eradicating the virus from the body appear unlikely with current approaches to treatment.

For these reasons, the development of the next generation of therapies remains a priority. Currently, all licensed antiretroviral medications are directed at one of two viral enzymes, but many new strategies are being pursued, including drugs that prevent the virus from entering a cell and approaches to boosting an infected person's immune response.

HIV Prevention

In developing countries where per capita health care spending may be only a few dollars per year, use of antiretroviral drugs is, in most cases, not feasible. Most developing nations lack the financial resources and health care delivery infrastructure necessary to support their appropriate use. Therefore, the identification of effective, low-cost tools for preventing HIV infection is crucial to slowing the epidemic.

Researchers have shown that many approaches to HIV prevention can reduce the number of new infections, including: education and behavior modification, the social marketing and provision of condoms, treatment of other sexually transmitted diseases and the use of antiretroviral drugs to prevent the transmission of virus from mother to infant. NIH has been pursuing these approaches to prevention both domestically and internationally through the HIV Network for Prevention Trials (referred to as HIVNET), and will continue to do so through a follow-on initiative, the NIAID Prevention Trial Network.

Prevention of Mother-to-infant transmission

In early 1994, the NIH-funded clinical trial known as ACTG 076 showed that mother-to-infant transmission rates could be reduced by as much as two-thirds by treating HIV-infected pregnant women and their newborn babies with an intensive regimen of AZT (zidovudine). Unfortunately, cost and many logistical issues preclude the widespread application of the ACTG 076 regimen in the developing world.

To surmount these barriers, NIH and CDC-supported researchers have been collaborating with the health ministries and scientists of several developing countries on research to identify simpler, less costly ways to prevent mother-to-infant transmission of HIV.

Several recently reported studies, including two in Thailand and the Ivory Coast (both supported by CDC), have shown that shorter regimens of AZT can also be beneficial, reducing transmission by between 37 and 51 percent. Despite these promising advances, widespread implementation of these proven regimens in most developing countries has not occurred because of their expense and their dependence on an infrastructure of good prenatal care.

Last week NIAID and the Health Ministry of Uganda reported on the exciting results of a study in Uganda that could have profound implications for the epidemic in children worldwide. This study showed that just two doses of the antiretroviral drug nevirapine—one dose administered to the mother at the onset of labor and one to her baby shortly after birth—reduced the risk of maternal-infant transmission of HIV by nearly 50 percent when compared with a similar brief course of AZT. What makes this finding so significant for the worldwide epidemic is that nevirapine is extremely inexpensive and easy to administer; the regimen costs approximately $4 and is 70 times cheaper than the prveiously studied regimens of short course AZT.

Topical Microbicides

Other methods of preventing HIV transmission also may have an important impact on slowing the epidemic. For example, researchers are developing and testing topical microbicides, substances that a woman could use in her vagina before sex to prevent the transmission of HIV and other sexually transmitted diseases. These interventions may help empower women to protect themselves in situations where they are unable to avoid sex with partners who may be HIV-infected or to persuade their partners to use a condom. Several studies have been conducted or are underway in Africa using a variety of products.

HIV Vaccine Development

The development of a safe and effective vaccine for HIV infection remains the ultimate goal of AIDS research, and a key step toward bringing the HIV epidemic under control around the world. To hasten HIV vaccine discovery, many public and private agencies have dramatically increased the resources devoted to HIV vaccine research. For example, at NIH, HIV vaccine funding increased by 93 percent between FY 1995 and FY 1999.

As part of this expanded effort, NIH has awarded numerous grants to foster innovative research on HIV vaccines, and is invigorating and reorganizing its vaccine clinical trials effort. In addition, NIH has established the Dale and Betty Bumpers Vaccine Research Center within the NIH intramural research program to stimulate multidisciplinary vaccine research.

Since 1988 more than 3000 healthy volunteers have enrolled in 52 (50 phase I and two phase II) NIAID-supported studies involving 27 vaccines. Recent studies supported by NIH in collaboration with several vaccine manufacturers have assessed so-called "vectored vaccines": harmless viruses (e.g. canarypox) that are genetically altered to make HIV proteins. Results have been encouraging: in phase I and phase II studies, this combination approach has appeared safe and evoked several types of immune responses that may have a role in protection from HIV.

Additional phase II trials of the combination vaccine concept will open later this year in Brazil, Haiti, and Trinidad and Tobago. These studies, as well as additional data that emerge from basic research, will provide the information to determine which products will advance into larger-scale testing. An exciting development for AIDS vaccine research was the initiation of the first AIDS vaccine study in Africa this spring. This NIH-supported phase I study, which is being conducted in Uganda, is designed to help determine whether it will be possible to design vaccines that work against more than one strain of HIV.

Meanwhile, a large-scale study of a vaccine based on the surface proteins of two HIV strains was recently undertaken in the United States by a private company—VAXGEN. An additional phase III study is being conducted by VAXGEN in collaboration with CDC in Thailand. NIH will collaborate with the company in evaluating the immunological responses to the vaccine.

Research Training

Training is a critical component of an international AIDS research and prevention program. Currently, the Fogarty International Center is working with several NIH Institutes to build HIV/AIDS research training and capacity in developing countries. Over the past decade, the AIDS International Training and Research Program, an arm of NIH’s vaccine research effort, has trained in the U.S. over 1,500 scientists from nearly 100 nations. This capacity-building effort has expanded research capabilities in a number of developing counties and has facilitated many NIH international HIV/AIDS research initiatives.

Conclusion

Two years ago, President Clinton set a national goal of having an effective HIV vaccine within 10 years. We are well positioned in our attempt to meet this goal with the extraordinary basic and applied research that is now under way. As we work to contain the global HIV/AIDS epidemic, it is essential that public and private sector partners strengthen their commitment to working together to speed HIV vaccine development, refine prevention efforts, and develop new treatments for those infected with the virus. Thank you for the opportunity to address this subcommittee.