AIDS at 25: Yesterday and tomorrow
analysis by Bob Roehr
AIDS researchers and advocates still remember the news 25 years ago.
"I was sitting in my office at NIH reading the article on five gay men in Los Angeles who presented with pneumocystis pneumonia, and felt a bit uncomfortable about it," said Dr. Anthony Fauci in recalling the first publication on a disease what would become known as AIDS. It appeared in the then-arcane journal Morbidity and Mortality Weekly Report on June 5, 1981.
Over the ensuing months, as the numbers grew, Fauci became both horrified and fascinated by the emerging infection. By the fall, "I changed the entire direction of my research to study this very unusual disease. Many of my mentors said I was making a career-destroying choice."
They couldn't have been more wrong. The decision put Fauci at the center of what "exploded into one of the most devastating pandemics in the history of civilization," as director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Â
The numbers are staggering: 25 million dead; 40 million people living with the disease; 5 million new infections and 3 million deaths around the world in the last year alone. More than a million Americans are living with the virus.
Frank Oldham, executive director of the National Association of People With AIDS, said that HIV in the U.S. increasingly is a disease of women and people of color. But he pointed out that more than 250,000 gay men of all colors have died of AIDS. "If you had to have a color attached to the epidemic, it is lavender. It's gay men who are white, gay men who Latino, gay men who are Asian, and gay men who are black. The epidemic is still lavender," he said.
HIV integrates itself into the DNA of host cells, creating reservoirs of the virus, "which has made eradication of HIV essentially impossible," said Fauci. Of the more than 60 million who have become infected, "not a single individual, on record, has been able to clear the virus completely, either with drugs or the immune system."
Still, in the U.S., the difference between the first 15 years of the epidemic, when living cadavers shuffled down the streets of gay neighborhoods, and the last 10 years has been like night and day.
Johns Hopkins University HIV researcher John Bartlett said, "The decade of HAART [highly active antiretroviral therapy] has been an extraordinary experience. In 1997 [with the introduction of protease inhibitors] we literally went from a clinic that prepared people to die to a clinic that prepared people to live. The sum total has been 3 million life-years saved. You cannot name another disease in medicine that has had that kind of progress in the last 50 years."
Regimens that originally were dozens of pills a day, often with food restrictions that made scheduling the dosing a compliance nightmare, are approaching the holy grail of a complete regimen in a single pill taken once a day â€“ at least for those on their first therapy who do not have a drug resistant virus.
The therapeutic marvel has begun to reach the developing world. "Now that we have very inexpensive generic drugs, the excuse that the drugs are too expensive is relevant but not prohibitive," said Fauci. "The assumption that you don't have the infrastructure to deliver the drugs, I think, is based on a lot of misperceptions â€“ Africa and Haiti have proven that to be incorrect. It is mostly political will."
Development of a preventive vaccine has been key to the control of most infectious disease over the last century. "With other viruses, 90-plus percent [of those infected] can clear the virus, even smallpox and polio," Fauci said. The trouble with HIV is that "the natural immune response is inadequate."
Fauci called this "one of the most important stumbling blocks" in developing a vaccine. "We are lookin
"We all think we need a vaccine and can't stop trying," said Bartlett. "But we have to move forward as if there is never going to be a vaccine." He pointed to 40,000 new HIV infections a year in the U.S., an estimate that hasn't changed from the early 1990s, when he said, "We haven't learned a thing about prevention, at least nothing that has that same impact" as with treatment.
One hopeful alternative is a microbicide, a gel or similar product that can be applied prior to having sex that reduces the transmission of HIV either by directly killing the virus or by preventing its passage through mucosal tissue to infect T-cells.
Large clinical trials are under way now in the developing world and, if all goes well, a first generation product could be on the market in just a few years. But early versions are not likely to work as well as a condom. And almost all of this work focuses on vaginal sex, it ignores the fact that millions of gay men, and even larger numbers of heterosexuals engage in anal sex.
The anti-HIV drug tenofovir does a brisk business on the street, purchased by those who believe it can help prevent HIV infection. Preliminary trials have been encouraging, but political charges have forced the cancellation of preventive trials overseas that might tell us for sure. Â
And even if it does work, who in the U.S. will pay for a drug costing more than $8,000 a year when condoms would cost 1 percent of that?
As for treatment, Fauci said, "We have more antiviral drugs that are approved by the FDA for HIV/AIDS than the sum total of all of the antivirals for all of the other viral diseases combined."
Bartlett added, "There are 64 drugs in the pipeline for HIV; that is more than for all bacteria combined. We don't need drugs up front, we need new drugs at the end where people fail." New classes of drugs â€“ entry inhibitors, integrase inhibitors, maturation inhibitors â€“ are in promising stages of development.
Tomorrow: Political will
"How are we going to pay for all of this?" asked Bartlett. "The cost of HAART is $12,000 to $14,000 a year. The new drugs are always more expensive than the predecessors. If we decrease mortality and increase the number of people that are living with HIV infection, the total AIDS bill is going to go up, it has to. We are expecting a crisis of how we are going to afford therapy in this country."
AIDS activist Dawn Averitt said, "The reality is that the U.S. bears 42 percent of the development cost of drugs. The companies can't continue to jack up prices because the system is going to buckle. Drugs are not ending up on the formulary and people are not getting access."
Science has responded well to the challenges of HIV in most instances. The principle stumbling blocks, both here and abroad, in the past and in the future, often are leadership and the political will to support prevention activities that work â€“ such as needle exchange and condoms â€“ and pay for expensive treatment that allows people infected with the virus to live long, productive lives.
Complacency with other infectious diseases â€“ syphilis, tuberculosis, malaria, measles â€“ has allowed their resurgence. HIV appears to be replaying the same scenario, only the price paid will be more deadly. The need for AIDS advocacy has not abated.