The nightmares and hallucinations began for Rae Lewis-Thornton two months ago.
"I had a dream someone attacked me in front of a policeman and he didn't come to my rescue," she says. "I never quite had dreams like this before."
Lewis-Thornton, 39, believes her mental problems are due to the new type of drug she is taking to kill the AIDS virus that has infected her immune system since 1986.
The drugs have extended her life as they have for tens of thousands of Americans living with HIV and with AIDS. But 20 years into the epidemic, they remain badly flawed.
The drug is the 20th or so medication she has had to take either daily or for months on end. The pills fight the virus and the opportunistic infections she has suffered, such as pneumonia and severe shingles.
"The longer I have had to take these pills, the harder it is," says Lewis-Thornton, a former political activist who worked on Jesse Jackson's presidential campaign. "It's the least amount of pills I have had to take. But the hallucinations, that's a great price."
Drugs Extend Life, But at a Cost
The drugs are imperfect: Experts say they only extend life, on average, 1.8 years for people with AIDS, and have many severe side effects. Some people live longer, others shorter, on the drugs. About 10 percent of AIDS deaths now are due to protease inhibitor-induced heart disease.
As an effective vaccine is at least 10 years away, drugs currently in development remain the hope for the 320,000 Americans living with AIDS and the other 500,000 who are infected with the virus. It takes about 10 years for HIV-positive people — who may have differing degrees of symptoms — to develop AIDS, characterized by the more severe disorders. These include cancer and infections, which a healthy immune system normally keeps in check.
"The AIDS epidemic shows what can be accomplished in biomedical research when resources are put to a problem" says Dr. Anthony Fauci, the director of the federal National Institute of Allergies and Infectious Diseases.
"With lots of money we have made many extraordinary advances. But we still need better drugs that are less toxic, more potent and more user- friendly."
Changing Treatments Over Time
Lewis-Thornton, who now lectures young people about AIDS for AIDS Action, an advocacy group in Washington D.C., has been living with HIV/AIDS for nearly as long as the epidemic's 20 years. Her treatment reflects how AIDS therapy has changed over the past two decades.
In the beginning, hospitals in New York City and San Francisco — then the epicenters of the epidemic — were overcrowded with AIDS patients. Without drugs, people with AIDS were dying less than a year after developing AIDS-related diseases, Kaposi's sarcoma, a cancer, and pneumocystis pneumonia.
Today, with antivirals and drugs treating the AIDS-related diseases, the hospitals have cleared out. AZT, the first drug to treat AIDS, a so-called reverse transcriptase inhibitor, was approved in 1987. But by 1993, patients were showing resistance to it and research showed that treatment with AZT did not decrease the onset of AIDS. Drugs similar to AZT were soon developed and gave physicians more options against resistance.
Lewis-Thornton took a high dose of AZT in 1989, because at the time it was believed it would kill the virus, even though those levels now are considered toxic. She says she constantly felt nauseated but took antacids to help her cope.
Her T-cell count fell anyway in 1992. T cells allow the body to fight infections. Healthy individuals have around 800 to 1,300 in a microliter, or about a teaspoon of blood. A person with AIDS has T-cell numbers below 200.
With such low levels, doctors diagnosed her as having AIDS, and said she needed additional medication. Her doctor recommended she take ddI, another reverse transcriptase inhibitor; an antibiotic to prevent pneumonia; an antifungal, since she was having chronic yeast infections, and an antidepressant.
"You had to grind ddI up like Alka-Seltzer, and it just tasted awful," says Lewis-Thornton. She took the antidepressant because she says, "it was hard to cope."
By 1993, she had her first bout with pneumocystis pneumonia and had become extremely skinny — wasting syndrome is another symptom of AIDS. Her doctor stopped her AZT and ddI, gave her two new antivirals, an appetite stimulant and continued the antifungals, the antibiotic and the antidepressant.
But in 1996, she had to be hospitalized with pneumocystis pneumonia and she received yet a new antibiotic to fight yet another opportunistic infection called mycobacterium avium complex.
Protease Inhibitors: A Major Advance
The year 1998 was a turning point. Lewis-Thornton had suffered two more bouts with pneumonia needing hospitalization and was very thin. But a new class of drug, the so-called protease inhibitors, approved in 1996, made a big difference.
"I got better," says Lewis-Thornton. "I gained weight. My T-cell numbers increased. My viral lode became non-detectable. My energy was improved. I could go shopping and cook when before I only had enough strength to do either one."
She was able to stop taking half her drugs, keeping to three antivirals, including the protease inhibitor, and one antibiotic.
While Lewis-Thornton now lives with the side effects of the current drugs she takes, her experience highlights the problems with treatment regimens for AIDS patients.
Half the people who try the medications do not respond to them and the side effects, such increased cholesterol levels and diabetes, may be so severe that the risk of taking the drug outweighs their benefits.
Lewis-Thornton experienced the protease inhibitor side effect that causes the redistribution of fat on the body. She gained enough weight to become a size 6, but the drug increased her girth on the upper part of her body to a size 12.
Taking the drugs also is not trivial. Some people take a dozen pills at different times during the day. Forgetting a pill can be lethal. During the time of a missed dose, a mutant virus can grow within a person's body that no longer responds to the medication.
Some current formulations of AIDS medications include more than one drug, making it easier for patients to take.
New Drugs in Development
While the reverse transcriptase and protease inhibitors affect two different aspects of the life cycle of the virus, new drugs in development take aim at other weak spots.
Reverse transcriptase inhibitors, for example, prevent the virus from making DNA out of the viral RNA. Protease inhibitors block the enzyme in the virus from breaking apart long strands of viral proteins to make smaller active HIV proteins that comprise the viral particle.
A new type of drug tries to stop the virus from fusing with the protein on the surface of T-cells, one of the earliest steps in the infection process.
Another aims to stop the viral enzyme integrase, which allows the virus to incorporate itself into the chromosomes of cells and perpetuate its presence in the infected person.
"If we have enough targets, we may be able to completely cripple the virus," says Kevin Robert Frost, vice president of clinical research and prevention programs at the American Foundation for AIDS Research, started in 1985.
"And if we have a broad enough armamentarium, over time, even if resistance develops there will be some virus still sensitive to a drug on the shelf that hasn't already been used."
The Pharmaceutical Research and Manufacturers of America says a little more than 100 new drugs are in testing either against the virus that causes AIDS or its resulting opportunistic infections. Currently 64 drugs have been approved, with either direct antiviral or other capabilities.
Most experts do not look to vaccines as the hope to stop AIDS in the near term. They say an effective vaccine might be another decade away.
Recent results in monkeys with a vaccine approach called "prime boost" — involving naked DNA containing HIV genes and a booster shot of another virus genetically engineered with HIV genes — have been promising, says Mark Harrington, of the Treatment Action Group, an organization that lobbies for more AIDS research and treatments.
The animals were not protected from getting infected, but they did not get as ill, he says. It could take another 10 years before this vaccine goes through the process of clinical trials to reach humans, if it even works, he says.
In 1996, early results from the protease inhibitors made the AIDS community believe that if patients took the drugs earlier, they might be able to eradicate the virus from their system. The federal government endorsed this approach in its treatment guidelines for the disease.
But in February, the federal government changed its policy regarding early treatment with protease inhibitors. It is now recommended that people wait until they become sicker before taking these drugs.
Less ill people can delay their potential exposure to side effects since to stay healthy people will probably need to take the drugs for the rest of their lives.
Lewis-Thornton is concerned that some people have become complacent about AIDS, believing that drugs are making it a manageable disease. She has been able to survive with AIDS but knows many people who have died. A total of more than 438,000 people in the United States have died from AIDS.
"People are naïve to think that AIDS cannot happen to you and that if it does, it's no big deal," says Lewis-Thornton. "HIV treatment requires a lot of work. I tell young people it is a burden they really don't want to have. If I didn't have HIV my life would have been completely different."