WASHINGTON, DC—The news about the number of AIDS cases is bad and getting worse, said Anthony S. Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases (NIAID), speaking to a science writers association here last month.
“In the United States, 980,000 people are living with AIDS. In the world, 42 million people have the disease—29.4 million in sub-Saharan Africa alone.”
According to calculations by the Centers for Disease Control and Prevention and NIAID, the next significant outbreaks will occur in Nigeria, Ethiopia, Russia, India, and China, he said. “In the next decade, 40 million more people will have AIDS, and by 2020, 70 million more people will die of it.”
In the United States, the numbers are smaller but no less depressing for what they represent. “We see 40,000 new infections every year, half of which are in people under age 25.”
Dr. Fauci said this “new generation” of HIV-infected individuals represents both a demographic shift and a “sense of complacency” among young male homosexuals who believe they are impervious to the ravages of the disease because of the new and highly effective drugs that are keeping their older associates alive and relatively healthy. They therefore have become somewhat lax about practicing safe sex.
Between 1999 and 2001, AIDS increased by 14% in gay men and 10% in heterosexuals, he said. The incidence is now 50% black, 29% white, and 19% Hispanic. Much of this new pattern is fueled by drug abuse, said Dr. Fauci.
Treatment Effective but Not Ultimate Answer
Highly active antiretroviral therapy (HAART)—protease inhibitors, reverse transcriptase inhibitors, and the new drug enfuvirtide (Fuzeon), approved in March—has proved to be extremely effective treatment for AIDS and is responsible for years of increased life and good health. Since 2001, when HAART was introduced, it has dramatically decreased the AIDS death rate. However, it is not without problems, Dr. Fauci related.
- The frequency and complexity of the various drugs that comprise HAART can be daunting (some patients take up to 36 pills a day), although some of the regimens have been simplified in recent years.
- The drugs are not without toxicity—for example, abnormal body fat distribution resulting in unsightly lumps and wasting of facial fat causing sunken cheeks, a telltale and embarrassing sign of HAART.
- The therapy has not been able to completely suppress viral replication, nor can it totally eliminate the persistence of viral reservoirs.
- Some patients eventually become resistant to HAART.
- The cost of the drugs is high, which means that the uninsured and others may be left in the cold.
Dr. Fauci enumerated the challenges that lie ahead in treating AIDS:
- Further simplifying the dose schedule.
- Improving tolerability by reducing toxicity.
- Penetrating the remaining viral reservoirs.
- Developing new drugs that target other stages of viral development.
Regarding the last, there is something promising on the horizon, Dr. Fauci said. In late March, NIAID released the news that Michael F. Summers, PhD, a Howard Hughes Medical Institute investigator and Professor of Biochemistry at the University of Maryland, Baltimore County, and his colleagues have discovered compounds that, in vitro at least, interfere with the assembly of HIV. This could lead to a new class of drugs called assembly inhibitors.
These compounds bind to HIV-1 capsid proteins and prevent them from assembling into the HIV capsid, the inner structure of the virus that houses viral RNA, enzymes, and other key viral components.
Although these compounds do not stop new viruses from assembling, they cause them to form with defective capsids, which cannot then infect new cells.
According to Dr. Summers, the combination of drugs that comprise HAART can interact with other drugs and weaken the effect of the “cocktail,” thus allowing resistant strains of HIV to emerge. Adding a new class of antiretroviral drugs, such as assembly inhibitors, to the mix may help solve the problem, although he says there is a long way to go before clinical trials can be initiated.
Treatment in Developing Countries
Political pressure to provide HIV/AIDS treatment in developing countries has gained intensity in recent years, Dr. Fauci said.
Since 95% of all AIDS exists in such places, there is no reason not to establish treatment programs there—despite lack of a health care infrastructure that those in developed countries are accustomed to and believe necessary.
“In the late 1990s, the price of AIDS drugs began to drop from many thousands of dollars per year per patient to only several hundred,” Dr. Fauci said. “Also, to withhold treatment from people in these countries could be construed as racist.”
However, one cannot simply drop off carloads of pills in Kenya or Tanzania and put the matter out of mind. There must to be a way to distribute the medicine, monitor patients' progress, and deal with toxicities.
“AIDS treatment has to be integrated with other health problems, and we need to train existing health care workers, recruit others, and perhaps in the future establish a research infrastructure,” he said.
The emergency plan announced by President Bush in this year's State of the Union speech will provide $15 billion over five years to accomplish these goals. The plan will target 14 underdeveloped countries, prevent seven million new infections, treat two million infected people, and care for 10 million people and their families who are affected by the disease.
Progress on the Vaccine Front
Despite the $500 million spent each year on AIDS vaccine research, there is unfortunately little encouraging news, Dr. Fauci said. But the effort continues and has resulted in a number of possibly effective vaccine strategies:
- Subunit vaccine, a structural piece of HIV produced by genetic engineering.
- Live vector vaccine, modified so it cannot cause disease.
- Vaccine combination—for example, a recombinant vector vaccine to induce cellular immune response followed by booster shots of a subunit vaccine to stimulate antibody production.
- Peptide vaccine, chemically synthesized pieces of HIV proteins.
- Virus-like particle vaccine that has some but not all HIV proteins.
- DNA vaccine which involves direct injection of genes coding for HIV proteins.
- Whole-killed virus vaccine.
- Live-attenuated virus vaccine from which one or more disease-causing genes have been removed.
“Vaccines for the communicable diseases we are all familiar with—measles, diphtheria, tetanus, and the like—are not like an AIDS vaccine, and one of the major reasons is the degree of exposure,” he said. “After all, how many times in your life are you exposed to diphtheria? Once or twice—or more likely, none.”
“But a sexually active person is exposed to HIV over and over again, and the greater the exposure to the disease, the less likely the vaccine will work.”
He named several other challenges: (1) Because HIV mutates and recombines, a vaccine needs to protect against the many strains of the virus; (2) HIV affects helper T-cells, and it is difficult to design a vaccine that must activate the very cells infected by the virus; (3) HIV can be transmitted as both free virus and infected cells, which may mean that more than one aspect of the immune system has to be stimulated; and (4) No one yet knows what constitutes an effective immune response to HIV, and there is as yet no ideal animal model.