AT MILE 20 OF THE New York marathon, Jim Howley started to feel sore, afraid he would have to walk the last six miles. His legs were gone, his energy spent. He was freezing. He decided to push it anyway, running as hard as he could for as long as he lasted. He made it to the end, finishing in just over 4i hours. But after the race, he was worried. ""I thought maybe I was doing permanent damage.'' That Friday, Nov. 8, he went to a lab for blood testing. ""I was scared to death. I thought they'd call me with real bad news.'' The news was good. His level of T-4 cells--the immune cells killed by the AIDS virus--was still relatively high. And he had no measurable trace of the virus in his blood.
In his Santa Barbara, Calif., home, Howley, 35, is still sunburned from an Ironman triathlon in Hawaii. He first tested positive for HIV 13 years ago, and was diagnosed with full-blown AIDS in 1989. His doctor gave him about a year and a half to live. Rather than give in to despair, he threw himself into exercise, determined to fend off the disease. But his T-cell count kept dropping. By last year, it had fallen to 3 (a healthy person has about 500 to 1,500). He was losing weight rapidly and his hair had started to fall out. He developed cytomegalovirus (CMV) retinitis, a potentially fatal opportunistic virus that left him partially blind in his right eye, then Kaposi's sarcoma, the deadly AIDS-related skin cancer marked by raw lesions. ""On paper, I was a corpse.''
In September 1995, Howley started on a new combination of drugs, including two that had just been rushed onto the market, Norvir and saquinavir. They belong to a barely tested class of AIDS medications called protease inhibitors, which attack the virus's capacity to replicate (page 68). His T-cells crept up from 3 to 5 to 7, a slight increase every month. Early this year they reached 69, then a month later, 260. Suddenly he was faced with an alien prospect: living. After so long, this, too, is a challenge. ""Now I'm going to have the same problems other people have,'' he says. ""For a while there I was released of all that. I didn't have to worry about the future. I didn't have to worry about retirement, getting older, looking bad. Now it's all come back,'' he says. ""But it's great.''
SINCE 1983, A DIAGNOSIS OF HIV-positive has been an automatic death sentence, one that has transformed communities, binding some together in solidarity and tearing others apart in fear. It now hangs over a million men, women and children in America, an additional 21 million worldwide. But in the last year, a handful of drugs have dramatically changed that prognosis. For years, people with AIDS had only one drug option, AZT; now there are nine, which can work in more than 100 different combinations, or ""cocktails.'' Already 60,000 Americans are taking the most popular protease inhibitor, Crixivan. ""For 14 years, everyone in this country has been conditioned to the idea that once you're infected with HIV, you're gonna die,'' says Stella Fitzgibbons, an AIDS doctor whose brother-in-law is having mixed results on the new drugs. ""The idea that these people will be able to stay with us and lead productive lives is really quite amazing. It's like a revolution.''
This is not the end of the plague. Not everyone can take the new medications, and no one knows how long the positive effects will last. Because the drugs are so expensive, costing up to $25,000 a year, they won't help the developing world, which now accounts for more than 90 percent of all adult AIDS or HIV cases. Even in this country, the poor and uninsured are often left out, coldly splitting the AIDS population into haves and have-nots. But despite these drawbacks, this year's breakthroughs do mark the end of our long-established way of thinking about the virus. Doctors are starting to consider HIV a chronic, manageable disease rather than a death sentence. Huge swaths of the American psyche in the age of AIDS--how we view sex, trust, responsibility--will have to change.
With the promise of the new drugs, new questions arise: How does a population psychologically braced to die suddenly get on with the business of living? If people start to see AIDS as no longer deadly, how do you get them to practice safe sex? When the wealthy feel secure, will the cause lose its celebrity and urgency? In an era of budget cuts, will the government still afford compassion toward those not helped by the drug? Finally, AIDS radically reshaped the gay community, brought it out of the closet; without the crisis, how will the community sustain itself?
For Chuck Johnson, 38, a San Francisco manager, the disease posed a somewhat simpler question. Last fall, he says, ""I didn't feel there was much reason to keep going.'' He had to feed himself through an IV in his arm because he couldn't tolerate food. His weight fell from 155 pounds to 125; his body was racked by esophageal CMV. A virus similar to warts covered his face. ""I didn't look very pretty,'' says Johnson. ""It wasn't my idea of life.'' His partner, Tom Lloyd, who is also HIV-positive, says he ""sat with him and watched him cry.'' In his sickness, Johnson pondered what he really wanted from life. Among more existential possibilities, a tangible answer presented itself: he wanted an Isuzu Rodeo, fully loaded. He cashed in half his life-insurance policy and paid cash for the car. His doctor had to sign a paper saying he would probably die within six months. The insurance company didn't ask for a second opinion.
Then Johnson began taking a cocktail of Crixivan, AZT and 3TC--22 pills a day, dispensed in a tackle box. Within a few weeks he started feeling better. His first reaction: ""I was angry.'' Prepared to die, he found it difficult to make the shift to life. ""What the f--k am I supposed to do now?'' He was angry at people who hadn't been through his ordeal, angry that they couldn't understand what it was like. He felt keenly the loss of a friend who had died last January, too soon to have tried the cocktail. And he had a hotshot car on his hands.
His financial dilemma is not uncommon. Jon Argenziano, who helps run the AIDS Action Committee support group in Boston, says some members have made remarkable recoveries only to realize, ""I thought I was going to be dead next year and I [owe] $25,000 on my credit cards. I've wiped out all my resources.'' Johnson sold the Isuzu, leased a more modest model and started exercising again. Although many AIDS patients fear that recovery will mean losing disability payments, Johnson isn't worried--yet. He's thinking about getting an M.B.A. and working for a nonprofit group. His viral load--the amount of the AIDS virus in his body--is lower than Lloyd's. They remain optimistic but wary. ""It's hopeful and it's cautious and it's wonderful and it's awful and it's empowering and it's diminishing,'' says Johnson. ""It's all of that at the same time.''
Stories like Johnson's and Howley's--and there are many--have become talismanic for AIDS patients and doctors. ""I go to work feeling like there's something I can do for my patients,'' says Dr. Harvey Makadon, a Boston AIDS specialist. ""I did not feel as clear about that a year ago.'' The success paradigm even has a name: the Lazarus effect. More drugs keep coming, more options, more time, more hope. It is a circle of life: all you have to do is stay alive until the next drug comes out, and the next, and the next.
But many people do not respond to the new drugs, or cannot tolerate them. Patients with long exposure to AZT seem to show small or short-lived improvement on the cocktail. And like AZT, the new chemicals can be extremely toxic. Cynara Chatman-Dillon, 43, a management consultant in Oakland, Calif., describes her four months on Crixivan: ""It felt like I was dying.'' She was violently nauseated and couldn't walk. Her viral load was dropping--""I was just thrilled''--but she would scream if anyone touched her. ""When I woke up finally in the fetal position with every muscle in my body on fire, I said, "That's it.' Talk about quality of life. There was none.'' She has now been off the cocktail for two months. Her viral load is rising and her T-cells are down to 90. Like many women of color, she is wary of the medical establishment because the drugs have been tested largely on white men. So Chatman-Dillon is looking for a woman doctor. And she's hoping for a new cocktail, hoping that her experience with Crixivan didn't leave her with ""cross-resistance'' to the other protease inhibitors.
EVEN SUCCESSFUL PATIENTS have reason to be watchful. The Lazarus effect may not last. Under pressure from AIDS activists, the Food and Drug Administration (FDA) hastened approval of the new drugs without long-term testing. Dr. Jerome Groopman, chief of experimental medicine at Beth Israel Deaconess Medical Center in Boston, is optimistic about protease inhibitors. He has overseen unimaginable recoveries, including that of David Sanford, an editor at The Wall Street Journal, who wrote movingly about his rebirth. But over the last two to four months, Groopman says, some patients have been ""showing signs of the benefits wearing off.'' This effect, too, has earned a name: crashing. Most people who have crashed were in the advanced stages of the disease before treatment, or had long histories with AZT. But since the drugs have been available for only a year, there is no telling how many will crash, or when.
In his Washington, D.C., support group, Gary Rose, 45, an AIDS treatment and research coordinator, has seen men career through all stages of hope and despair. First there arose ""this unspoken conflict between the people the drugs were working for and those who they're not working for.'' One man who had been very sick got much better, buoying the hopes of others. Now, Rose says, ""his viral load has shot back up again and no one knows why. Seeing that Lazarus experience starting to fail has made everyone very jumpy. The fear is that some of us have almost no immune system left, so we may not have enough immune system for these medications to latch onto.'' Rose, who tested positive in 1985, says he has become afraid to dream. ""I spent a long time divesting myself of all my dreams. What if everything falls through again? How can I go through all that again?''
William Krantz would like the opportunity just to take that chance. Krantz, 30, a cook and waiter in Indianapolis, tested positive for HIV in July 1995, and his T-cell count is falling. He is uninsured. His take-home pay--$11,000 a year at most--is nowhere near enough to pay for treatment. If he were indigent or disabled, he might be able to get the drugs through Medicaid, which covers half of the nation's AIDS patients. But for people like him, working people with limited resources, coverage is spotty. Some manage to enroll in trial programs with the drug companies or medical schools. Others get drugs through the state and the federally funded ADAP (AIDS Drug Assistance Program). But Indiana is one of 35 states whose ADAP, as of September, did not cover protease inhibitors.
To a great extent, the drugs emerged faster than the systems to pay for them. In the last month the federal government poured an emergency $167 million into the strained ADAP system. The hardest-hit states--New York and California--offer the best access to the drugs. Other states have set up lotteries to dispense the drugs to a lucky few, a grim way to parcel out possible life or death. Missouri, for example, will choose 75 people from among 2,639 needing assistance.
In Indiana, Krantz has been on a waiting list since last December just to get AZT. Already he has $1,000 in medical bills he can't pay. He does not even know how fast his disease is progressing because he can't afford a viral-load test, which costs an additional $250. When he hears the Lazarus stories, their promise comes laced with anguish. ""I feel that I should be on any number of protease inhibitors right now, but I can't get them. It's so frustrating.''
Cases like Krantz's are especially haunting as HIV has changed its path. Though often associated with gay white men, the virus now hits hardest in poor and minority communities. The infection rate among African-Americans is five times higher than among whites. Conditions are even more acute in prisons. ""This is the epidemic,'' says Richard Marlink, executive director of the Harvard AIDS Institute. ""The average person infected with HIV is of color.'' For many, the new drugs are out of reach, a tragedy reminiscent of malaria and tuberculosis--we have a cure, but millions die anyway because they can't afford it. ""In our own communities,'' says Marlink, ""the have-nots are just like people in developing countries. It's a dangerous public-health message to represent these drugs as the first step in the end of the epidemic.''
In many cases, money alone is not the issue. Combination therapies require incredibly demanding regimens--sometimes as many as 30 or 40 pills a day, distributed over a strict timetable. Some drugs have to be taken with food, others on an empty stomach. And if patients fall off the regimen, they risk cultivating a strain of the virus that's resistant to one or more of the drugs. For drug injectors, or for people with unstable housing or food supply, this hurdle can be insurmountable. ""One of the drugs, ritonavir, requires refrigeration,'' says Victoria Sharp, codirector of the AIDS program at Beth Israel Medical Center in New York. ""Well, we have patients who don't have refrigerators. Another one requires you to maintain a low-fat diet and eat at particular times. Some patients access their meals through soup kitchens, so they have no control over dietary fat or timing.''
New York's Dr. Doug Dietrich is an HIV specialist who helped write AIDS guidelines for Blue Cross/Blue Shield, insurers for one in four Americans. He speaks in the bland, pragmatic language of his trade. In discussing access to the new cocktails, he talks of ""screening for compliance,'' an innocuous locution for a form of actuarial Darwinism. ""If you give protease inhibitors to people who are not compliant, they're really a waste,'' he says. ""It's tantamount to flushing them down the toilet.'' S. J. Avery, executive director of Bronx AIDS Services, calls the resulting process, with equal blandness, ""deselection.'' What it means is that she fears her clients, hardest hit by the virus, may be deselected for treatment because they fit the stereotype of patients who cannot adhere to the regimen. To add insult, some fear being scapegoated as potential breeders of a drug-resistant supervirus.
Also, as AIDS shifts to poor communities, it plays to the phenomenon known as compassion fatigue. At the AIDS support group PAWS/LA, for example, individual donations are down 25 percent in the last year. ""As more people feel the crisis is over,'' says Joel Kimmel, director of development, ""the people who gave $5 and $10 checks are moving on to other causes--the environment, cancer--and the larger institutions are going back to schools, the opera.'' Jim Graham, who runs the Whitman-Walker Clinic in Washington, D.C., which relied on $10 million in donations for 1996, fears that 3 to 10 percent of donors will ""flake off. In a world of competing woes, many just want to wash their hands of [AIDS] rapidly and treat it the way we treat something like heart disease. By that I mean, heart disease is important, but it doesn't have an emergency sense about it.'' Marlink of Harvard is more blunt. The message that middle-class white males are doing better, he says, ""makes it that much harder to raise interest, funds and collaboration. It's harder to get national funding around specific populations that don't reflect the average elder, white senator.''
An even bigger danger is complacency. Americans have greatly struggled with safer sex and safer injection practices. However well known the risks, the reality is that sometimes getting a clean needle or a condom is too much trouble. The new drugs make it even harder to stay safe. Chris Dechant, who hosts a syndicated gay radio show out of Chicago, says he has already seen a new sexual carelessness. Dechant, 36, is HIV-positive; a close friend on the cocktail is dying. ""I've heard this out on the street: "Why worry about it? Why use a condom? Isn't it like herpes? I can take a pill and get rid of it'.'' In theory, a person taking the cocktail can infect partners with drug-resistant strains of the virus. This has already happened with AZT. About 20 percent of Americans with AIDS today are resistant to the drug because they got the disease from someone taking it.
For Jim Howley, the marathon runner, these worries may be real, but they are abstract. He lives on more material readings: T-cell counts, viral-load measurements, the constant effort to get into trials for newer drugs. After he tested positive, he hurled himself into excess: obsessive exercise, but also too much cocaine, too much work. Now he volunteers two days a week as a therapist at a gay and lesbian group. He and his partner of five years just had a commitment ceremony; they're looking into long-term investments and IRAs. ""Now I have to find a job,'' he says--one with good insurance. In March he wants to run, swim and bike across the country to spread a message that the disease can be beaten. ""It's just incredible. And it's not just me. It's so many people it's happening to.''
Behind his story, of course, lie the faces of others who will never get the drugs, or for whom they won't work. But behind these, also pressing, also painful, are the faces of those who died too soon, never knowing the hope that even the most unproven remedies can offer. Some are our friends, our family, our loved ones. If this is the end of the beginning, bring on the beginning of the end.
Over the past decade the FDA has approved nine drugs--six RT inhibitors and three protease inhibitors--to combat the AIDS virus. None of them is very effective by itself, but researchers are finding that certain three-drug combinations can shackle HIV for long periods.
Reverse Transcriptase Inhibitors 1987 AZT (Retrovir) Glaxo Wellcome 1991 ddl (Videx) Bristol-Meyers Squibb 1992 ddC (HIVID) Hoffman-La Roche 1994 d4T (Zerit) Bristol-Meyers Squibb 1995 3TC (Epivir) Glaxo Wellcome 1996 Nevirapine (Viramune) Boehringer Ingelheim Proterase Inhibitors 1995 Saquinavir (Invirase) Hoffman-La Roche 1996 Indinavir (Crixivan) Merck & Co. Ritonavir (Norvir) Abbott Laboratories
More than a half-million Americans have been stricken by AIDS. The caseload is still rising for blacks and Hispanics.
Number of AIDS cases diagnosed through June 1996 Men White 237,236 Black 143,578 Hispanic 79,808 Asian/Pacific 3,411 Native American 1,212 Women White 19,225 Black 45,417 Hispanic 16,805 Asian/Pacific 415 Native American 227 Number of AIDS cases per 1,000 population Men White 2.2 Black 9.0 Hispanic 5.6 Asian/Pacific 0.7 Native American 1.0 Women White 0.2 Black 2.6 Hispanic 1.2 Asian/Pacific 0.1 Native American 0.2
