Seven years ago, John McCarthy woke up from heart surgery with a smile on his face, drawing a puzzled expression from a doctor who expected to see a man in despair.
"I never thought I'd live long enough to have a heart attack," McCarthy told the physician, a Johns Hopkins psychiatrist.
An alcoholic and drug addict, McCarthy had tested positive for the AIDS virus in the late 1980s - when doctors could offer little effective treatment, and many of his fellow drug users were wasting away and dying.
But now, on the 25th anniversary of the first case reports of AIDS, the 50-year-old McCarthy is one of many success stories, a beneficiary of powerful drug combinations that have made the dream of long-term survival a reality.
McCarthy, a former biker who sports a thick mane of gray hair and a bushy mustache, has lived long enough to kick drugs and booze, record songs with a band, counsel other patients and plan for the future.
"This represents the triumph of therapeutic optimism," said Dr. Glenn J. Treisman, the psychiatrist who visited McCarthy after his operation. "Very difficult patients are not untreatable; they are just difficult to treat."
Pharmaceutical development has slowed considerably since the mid-1990s, when three-drug "cocktails" revolutionized the treatment of HIV/AIDS. Even so, the outlook could grow brighter with a one-pill regimen nearing government approval and new classes of anti-viral drugs expected to reach the market in the next two years.
"People are living quite long, and it's a remarkable success story," said Dr. John Bartlett, the chief of infectious diseases at the Johns Hopkins School of Medicine and one of the nation's foremost AIDS experts. "It's remarkable what we now have to offer, and it's extended beyond that into a global health effort."
Still, the epidemic rages around the world - particularly in regions of Africa and Asia, where advanced treatments are just beginning to reach the poor. All told, almost 40 million people worldwide are infected, with millions of children orphaned and some economies in ruins.
Last week, the Joint United Nations Programme on HIV/AIDS reported that the epidemic is slowing down but still outdistancing efforts of public health organizations. Last year, 4.1 million people became infected and 2.8 million died. All told, 21 million have died since the epidemic began.
"The epidemic continues to outpace us," U.N. Secretary-General Kofi Annan told the U.N. General Assembly on Friday. "There are more new infections than ever before, more deaths than ever before, more women and girls infected than ever before."
Today marks a quarter-century since the Centers for Disease Control and Prevention published a case report of five gay men in Los Angeles who suffered from a rare form of pneumonia that strikes only people with ravaged immune systems. The underlying disease would later become known as acquired immune deficiency syndrome, or AIDS.
First, it killed gay men who spread the virus through unprotected sex, then addicts who passed the needles they used to inject heroin and cocaine. Needle-sharing contributed heavily to the HIV/AIDS problem in Baltimore, which by 2004 had the fifth-highest per-capita infection rate in the nation.
"I know whole blocks in East Baltimore where mothers and fathers and grandchildren all shared needles," McCarthy said.
But the virus did not discriminate. Men passed the virus sexually to women, and women to men. Pregnant women transmitted it to their babies. A generation of hemophiliacs perished after contracting the virus from blood products they depended upon to live.
"It was a strange disease," said Bartlett, recalling his first AIDS patient - a female drug user who had lost 60 pounds and quickly died of the once-rare Pneumocystis carinii pneumonia. "The patients were terribly stigmatized. People didn't like the people who got it, either gay men or injection drug users, or they feared they'd get it by being in the same room or touching the same pencils.
"And everybody died."
A test developed in the mid-1980s by Dr. Robert Gallo, a government scientist who now heads the Institute of Human Virology in Baltimore, enabled laboratories to screen blood donations for the virus. It also enabled patients to find out whether they were infected and enter treatment.
McCarthy tested positive six years before the introduction of triple-drug combinations that suddenly transformed AIDS into a chronic, manageable disease that many people could live with.
An employee at a state psychiatric hospital, McCarthy had seen the withered frames and hopeless expressions of patients who battled HIV/AIDS along with their mental afflictions. He watched doctors examine their swollen lymph nodes, and when his own started to "explode under the armpit, in back of my skull, under my throat, behind the knees," he knew what was wrong.
"First I went crazy," said McCarthy, who lives in a Glen Burnie apartment crammed with tropical fish tanks and musical equipment. "My substance abuse and alcohol use increased. It was a death sentence. I felt it was better to die of a drug overdose than have this on your death certificate."
The waiting room at the Johns Hopkins Moore Clinic was a dimly lit place filled with dying people, he said. But there, a miracle occurred.
Treisman and others in the mental health service treated his depression and helped him shake his addictions. By the time the new drugs came along, McCarthy had gained enough control of his life to manage the complicated dosage schedules and deal with the side effects that the HIV/AIDS regimens entailed.
At first, he was taking several different pills three times a day. One of them caused hallucinogenic dreams, and others triggered stomach and intestinal distress. But the side effects were tolerable, McCarthy said, as long as he took his medications on schedule and stayed away from fatty foods. His immune system, which had sunk to a level just above the threshold for full-blown AIDS, steadily improved.
By that time, scientists knew they had to fight the virus on different fronts. If they prescribed only one anti-viral medication, as they did before 1996, the virus would rapidly evolve, changing its genetic makeup to evade treatment. Then patients had to switch to another drug, and another, often with poor results.
But McCarthy and other patients on three-drug combinations saw their viral load - the concentration of HIV in their bloodstream - plummet to undetectable levels. This gave their immune systems a chance to rebound. They gained weight and rejoined the living.
Today, doctors are seeing patients who have lived with the virus for 10, 15, even 20 years. Some eventually die of AIDS-related infections, but many die of illnesses not directly related to the virus.
"A lot are dying of liver disease due to recurrent hepatitis or alcoholism," said Bartlett. "A lot are dying of the things they used to die of because they are injection drug users," such as overdoses.
Dr. Albert Wu, a Hopkins internist, said some patients live long enough to develop diseases of aging, such as heart attack or stroke.
Today, doctors look forward to a new wave of drugs, now in clinical trials, that will add weapons to their arsenal. Some are called entry inhibitors because they block the virus from getting inside the white blood cells they seek to infect. Others are called integrase inhibitors because they block an enzyme that the virus uses to splice itself into a patient's DNA.
Dr. Patrick McLeroth, clinical director at the Chase Brexton Clinic in Mount Vernon, said the new drugs may be most useful for patients who have shifted from one regimen to another and are running out of options.
"There's nothing to say that they couldn't be used for someone who hasn't been on medications," he said. "But for now, they're probably for patients in deep salvage, patients who have failed multiple regimens."
Although drug companies haven't unveiled a new class of medications since protease inhibitors in 1996, treatment has become simpler. Whereas patients once had to take medications virtually around the clock, some now manage on just two tablets, taken once a day.
Drug developers achieved this by combining two drugs in one pill. They have also found ways to work with the body's metabolism to keep levels of their drugs in the bloodstream high without frequent dosing, he said.
Therapy could become even simpler if the Food and Drug Administration, as expected, approves a single-pill regimen developed by Gilead Sciences and Bristol-Myers Squibb.
The pill, which combines three medications, isn't more powerful than what's now available, doctors say. "But I think it does mean a lot symbolically," Bartlett said. "It means we've gotten to the ultimate simplicity."
For many AIDS researchers, the greatest disappointment has been the failure to develop an effective vaccine. Lacking that, many believe that the greatest challenge of the next decade will be providing treatments and spreading medical know-how in sub-Saharan Africa, India, China and other poor regions of the world.
"That will be the biggest story, period," said Gallo of the Institue of Human Virology, which is involved in several African nations. "At least in some African countries, we see it working and working well."
The key, he said, is not just pouring money into medications but training doctors and nurses in the nuances of treatment. "But this is lifelong therapy, whether you're in Africa or the U.S. or Europe," Gallo said. "It's constant."
Dr. Thomas Quinn, an infectious-disease specialist at the Johns Hopkins School of Medicine, said doctors have discovered that they don't need the 24 drugs available in the United States to treat suffering patients in Africa. Because most went untreated until recently, they didn't have the chance to develop the drug resistance common to patients who have tried multiple therapies in the U.S.
"We started out with a treatment-naive population, so you don't have resistance," Quinn said. "You can now start with one good drug regimen, and as long as [patients] are adherent, you can hold back the resistance threat."