About the Director

Worldwide, more than 29 million people have been infected with the human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). This figure is projected to reach at least 40 million cases by the year 2000; an estimated 7,500 adults and 1,000 children worldwide become infected with the virus each day. The epidemic continues to accelerate rapidly in certain parts of the world, notably in sub-Saharan Africa, India and southeast Asia. Globally, at least 8.4 million individuals with HIV/AIDS have died, including more than 380,000 people in the United States.

Despite the mounting toll of HIV in this country and abroad, recent developments have provided some measure of optimism. In the United States, AIDS deaths dropped 23 percent from 1995 to 1996, and new AIDS diagnoses declined by 6 percent. These trends are probably due to several factors, including the increased use of combination therapy with potent antiretroviral drugs; improved prevention and treatment of the infections associated with HIV disease; the growing experience and skill of the medical community in caring for HIV-infected people; improved access to care for those infected with HIV; and the success of prevention efforts.

Significant progress also has been made in understanding the fundamental mechanisms of the HIV disease process, allowing us to formulate new strategies for treating HIV-infected people.

However, the fight against HIV/AIDS is far from over. While the overall number of new AIDS cases in the United States dropped between 1995 and 1996, heterosexual cases rose by 8 percent. Thousands of Americans will die from AIDS this year, and many more, especially disenfranchised people in our inner-cities, will be newly infected. Elsewhere in the world, particularly in developing countries where access to AIDS drugs may be virtually non-existent, the epidemic continues to accelerate. Research into a vaccine and other means of preventing HIV infection is crucial to slowing the epidemic in these settings as well as in our own country.

Progress in Antiretroviral Therapy

Ten years ago, we had only one option for treating HIV -- single-drug therapy with AZT -- which had a modest and short-lived benefit for patients with advanced HIV disease. Approximately 3 years ago, two-drug therapy was shown to benefit HIV-infected patients with moderate immunodeficiency. Today, treatment combinations which include a class of medications that inhibit the HIV protease enzyme ("protease inhibitors") can control the replication of HIV in many patients to a degree and for a duration not previously possible. The development of protease inhibitors is a classic example of basic research findings being translated into practical applications that benefit patients. Fundamental research into the structure and function of HIV protease allowed scientists to develop highly specific agents that block the enzyme, and hence the replication cycle of the virus.

Currently, eleven different antiretroviral drugs to treat HIV infection, including four protease inhibitors, are licensed in the United States. Expert panels convened in 1996 and 1997 by the Department of Health and Human Services, the National Institutes of Health (NIH), and other organizations have analyzed the many recent advances in antiretroviral therapy and developed specific treatment recommendations for HIV-infected adults and children. In 1997, the central principle of antiretroviral therapy is to reduce the amount of HIV in the body to the lowest possible level for as long as possible, with the goal of forestalling disease progression. In the past two years, a number of clinical trials have demonstrated that triple-drug combinations that include protease inhibitors can reduce plasma levels of HIV to undetectable levels in many HIV-infected individuals. Several different drug combinations have been shown to provide either virologic or clinical benefit to patients, albeit in the relatively short-term. Unfortunately, many patients have not benefited from the currently available drugs, or have been unable to tolerate their side effects. We are hopeful that patients who have done well on triple-drug therapy will continue to do so, but cannot say with certainty whether the benefits of these drug combinations will be sustained, or if cumulative toxicities and the development of resistance will limit the long-term utility of these regimens.

Therefore, the development of the next generation of therapies remains a priority. Together with our partners in academia and industry, the NIH is pursuing many treatment strategies that target other phases of the viral life cycle, such as the initial binding of th virus to its target cell and the process whereby viral genes integrate themselves into the DNA of an infected person's cells. Such research also helps patients with other conditions. For example, lamivudine (3TC), developed as an AIDS drug, has been shown to potently suppress hepatitis B virus replication in patients chronically infected with that virus.

Researchers also are exploring ways to boost an HIV-infected person's immune system. As an example of this, NIH researchers have used the immune system molecule interleukin-2 as a therapy to substantially increase CD4+ T cell levels; this effect has been observed for more than four years in some patients. The principles established by this research may also prove relevant to other diseases characterized by decreased T cell function, and to certain kinds of cancers.

As we approach the 21st century, realistic goals for HIV therapy include:

• Potent new combinations of non-toxic anti-HIV drugs that can be administered early in the course of HIV infection to significantly prolong the period in which a person remains free of serious symptoms;
• Orally administered preventive drugs and treatments for all commonly encountered opportunistic infections;
• Safe and effective therapies that boost the immune system.

Progress in AIDS Vaccine Development

Despite important advances in HIV therapeutics, it remains critical to vigorously pursue the development of a safe and effective HIV vaccine, as President Clinton has articulated. At the NIH, we have formulated a balanced strategy for HIV vaccine development. Basic research is helping to answer important questions about HIV and the immune responses that might protect an individual from HIV infection or prevent the progression of disease. To speed the pace of discovery, the NIAID recently awarded 58 grants to foster innovative research on HIV vaccines. Parallel with these efforts, we continue to test candidate vaccine products in small-scale clinical trials. Our early efforts with single product regimens have given way to more complex strategies. One such approach involves priming the immune system with a harmless virus genetically engineered to make HIV proteins, and then boosting the immune response with a purified HIV protein. A Phase II trial employing this approach recently opened and will enroll 420 volunteers in 12 U.S. cities.

The NIH has also begun development of a Vaccine Research Center (VRC) within the NIH intramural research program, co-sponsored by NIAID and the National Cancer Institute, to stimulate multidisciplinary research into basic and clinical immunology and virology, and ultimately vaccine design and production. A national search is underway to recruit the first director of the VRC.

Concomitant with efforts in vaccine development, the NIH and our sister agencies are pursuing other approaches to HIV prevention, such as education and behavior modification, the development of topical microbicides to protect women from HIV and other sexually transmitted diseases, and new ways to prevent maternal-fetal HIV transmission.

Recent progress in HIV research has been extraordinary, yet much remains to be accomplished. I am confident that continued support of basic and applied research will lead to an even greater understanding of HIV pathogenesis, as well as to the development of improved therapies and an HIV vaccine.