An Open Letter to Dr. Anthony Fauci

The Press of Freedom: A Column Open to Our Readers

I have been screaming at the National Institutes of Health since I first visited your Animal House of Horrors in 1984. I called you monsters then and I called you idiots in my play, The Normal Heart, and now I call you murderers.

You are responsible for supervising all government-funded AIDS treatment research programs. In the name of right, you make decisions that cost the lives of others. I call that murder.

At hearings on April 29 before Representative Ted Weiss and his House Subcommittee on Human Resources, after almost eight years of the worst epidemic in modern history, perhaps to be the worst in all history, you were pummeled into admitting publicly what some of us have been claiming since you took over three years ago.

You admitted that you are an incompetent idiot.

Over the past four years, $374 million has been allocated for AIDS treatment research. You were in charge of spending much of that money.

It doesn’t take a genius to set up a nationwide network of testing sites, commence a small number of moderately sized treatment efficacy tests on a population desperate to participate in them, import any and all interesting drugs (now numbering approximately 110) from around the world for inclusion in these tests at these sites, and swiftly get into circulation anything that remotely passes muster. Yet, after three years, you have established only a system of waste, chaos, and uselessness.

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It doesn’t take a genius to announce that you have elected to personally supervise the study of a broad range of new drugs. Yet, two years later, you are forced to admit you’ve barely begun.

It doesn’t take a genius to request, as you did, 126 new staff persons, receive only 11, and then keep your mouth shut about it.

It takes an incompetent idiot.

To quote Representative Henry Waxman at the above hearings: “Dr. Fauci, your own drug selection committee has named 24 drugs as high priority for development and trials. As best as I can tell, 11 of these 24 are not in trials yet. Six of these drugs have been waiting for six months to more than a year. Why the delays? I understand the need to do what you call setting priorities but it appears even with your own scientists’ choices the trials are not going on.”

Your defense? “There are just confounding delays that no one can help… we are responsible as investigators to make sure that in our zeal to go quickly, that we do the clinical study correctly, that it’s planned correctly and executed correctly, rather than just having the drug distributed.”

Now you come bawling to Congress that you don’t have enough staff, office space, lab space, secretaries, computer operators, lab technicians, file clerks, janitors, toilet paper; and that’s why the drugs aren’t being tested and the network of treatment centers isn’t working and the drug protocols aren’t in place. You expect us to buy this bullshit and feel sorry for you. YOU FUCKING SON OF A BITCH OF A DUMB IDIOT, YOU HAVE HAD $374 MILLION AND YOU EXPECT US TO BUY THIS GARBAGE BAG OF EXCUSES!

The gay community has been on your ass for three years. For 36 agonizing months, you refused to go public with what was happening (correction: not happening), and because you wouldn’t speak up until you were asked pointedly by a congressional committee, we lie down and die and our bodies pile up higher and higher in hospitals and homes and hospices and streets and doorways.

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Meanwhile, drugs we have been begging that you test remain untested. The list of promising untested drugs is now so endless and the pipeline so clogged with NIH and FDA bureaucratic lies that there is no Roto-Rooter service in All God’s Christendom that will ever muck it out.

You whine to Congress that you are short of staff. You don’t need staff to set up hospital treatment centers around the country. The hospitals are already there. They hire their own staff. They only need money. You have money. YOU HAVE $374 MILION FUCKING DOLLARS, FOR CHRIST’S SAKE.

The gay community has, for five years, told the NIH which drugs to test because we know and hear first what is working on some of us somewhere. You couldn’t care less about what we say. You won’t answer our phone calls or letters, or listen to anyone in our stricken community. What tragic pomposity!

The gay community has consistently warned that unless you move quickly your studies will be worthless because we’re already taking drugs into our bodies that we desperately locate all over the world (who can wait for you?!!), and all your “scientific” protocols are stupidly based on utilizing guinea-pig bodies that are clean. You wouldn’t listen, and now you wonder why so few sign up for your meager assortment of “scientific” protocols that make such rigid demands for “purity” that no one can fulfill them, unless they lie. And why should those who can obtain the drugs themselves take the chance of receiving a placebo in one of your “scientific” studies?

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How many years ago did we tell you about aerosol pentamidine, Tony? This stuff saves lives. And we discovered it ourselves. We came to you, bearing this great news on a silver platter, begging you: can we get it officially tested; can we get it approved so insurance companies and Medicaid will pay for it (as well as other drugs we beg you to test) as a routine treatment, and our patients going broke paying for medicine can get it cheaper? You monster.

“Assume that you have AIDS, and that you’ve had pneumonia once,” Representative Nancy Pelosi said. “You know that aerosolized pentamidine was evaluated by NIH as highly promising… You know as of today that the delays in NIH trials… may not be solved this year… Would you wait for [an NIH] study?”

You replied: “I probably would go with what would be available to me, be it available in the street or what have you.”

We tell you what the good drugs are, you don’t test them, then YOU TELL US TO GET THEM ON THE STREETS. You continue to pass down word from On High that you don’t like this drug or that drug — when you haven’t even tested them. THERE ARE MORE AIDS VICTIMS DEAD BECAUSE YOU DIDN’T TEST DRUGS ON THEM THAN BECAUSE YOU DID.

You’ve yet to test imuthiol, AS101, dextran sulfate, DHEA, Imreg-1, Erythropoietin — all drugs Gay Men’s Health Crisis considers top priority. You do like AZT, which consumes 80 percent of your studies, even though Dr. Barry Gingell, GMHC’s medical director, now describes AZT as “a cumulative poison… foisted on the public.” Soon there will be more AIDS patients dead because you did test drugs on them — the wrong drugs.

ACT UP was formed over a year ago to get experimental drugs into the bodies of patients. For one year ACT UP has tried every kind of protest known to man (short of putting bombs in your toilet or flames up your institute) to get some movement in this area. One year later, ACT UP is still screaming for the same drugs they begged and implored you and your world to release. One year of screaming, protesting, crying, cajoling, lobbying, threatening, imprecating, marching, testifying, hoping, wishing, praying has brought nothing. You don’t listen. No one listens. No one has ears. Or hearts.

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Whose ass are you covering for, Tony? (Besides your own). Is it the head of your Animal House, the invisible Dr. James Wyngaarden, director of the National Institute of Health (and may a Democratic president get him out of office fast)? Is it Dr. Vincent DeVita, head of the National Cancer Institute, another invisible murderer who lets you be his fall guy? Or Dr. Otis Bowen, secretary of the Department of Health and Human Services, no doubt the biggest murderer on the list; Shultz and Weinberger would never take such constricting shit from the Office of Management and Budget. All the doctors have continuously told the world that All Is Being Done That Can Be Done. Now you admit that isn’t so.


I don’t know (though it wouldn’t surprise me) if you kept quiet intentionally. I don’t know (though it wouldn’t surprise me) if you were ordered to keep quiet by Higher Ups Somewhere. You are a good lieutenant, like Adolph Eichmann.

I do know that anyone who knows what you have known for three years — that, to quote Ted Weiss, “the dimension of the shortfall is such that you can’t possibly meet our needs,” and, to quote the New York Times and their grossly incompetent AIDS reporter, Philip Boffey (whose articles read like recycled NIH releases): “Officials Blame Shortage of Staff for Delay in Testing AIDS Drugs” — I repeat, anyone who has known all this and denied it for the past three years is a murderer, not dissimilar to the “good Germans” who claimed they didn’t know what was happening.

With each day I realize a little more that the gay community has lost the battle. And that we haven’t begun to experience the horrors that still await us —  horrors even worse than you now embryonically signify. We have lost. No one important enough has ears. Or hearts.

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You care, I’m told (although I no longer believe it). I’ve even heard you called a saint. You are in essence a scientist who’s expected to be Lee Iacocca. But saints, miracle workers, good administrators, brilliant scientists have imaginations vivid enough to know how to spend $374 million in a dire emergency. You have no imagination. You are banal (a word used so accurately to describe Eichmann).

Do I want you to leave? (Yes.) Could you’re replacement possibly be more pea-brained than you? (Yes, it is possible.) Will this raving do any good at all? Will it make Congress shape you up? Will it make my own communities bureaucratically mired AIDS organizations finally ask the right questions? (Judy Peabody of GNHC please take note.) Will Dr. Mathilde Krim ever — as she indicated she would — get the American Foundation for AIDS Research to fund the desperately needed and desperately needy Community Research Initiative, which is valiantly attempting to do what you should be doing, so tired we are of waiting for you to do it? (Leonard Bernstein and Harry Kraut please take note.)

I have no answers to most of these questions. You may (God help us all) be the best that will be given us. You may, like John Ehrlichman, once accused, seek redemption and forgiveness by rethinking, retooling, and, like Avis, trying harder. Even more miraculous, those Supreme Murderers in the White House might tomorrow acknowledge that families simply everywhere have gay sons and daughters.

But I fear these are only pipe dreams and you’ll continue to carry on with your spare equipment. The cries of genocide from this Cassandra will continue to remain unheard. And my noble but enfeebled community of the weak, and dying, and the dead will continue to grow and grow — until we are diminished.


David France on the Plague Years: The history and survival of ACT UP

“Death wasn’t being responded to as a public health problem,” David France says. “It was dealt with with sniggers. It was left to religious leaders to explain or respond to the epidemic. And they responded by calling it the wrath of God.”

He adds: “That’s the hostility we all saw in the beginning, the early days. It was certainly the first of many major hurdles that AIDS activism had to climb.”

France’s first film, How to Survive a Plague, works as a primer to his investigative journalist—he has written at length about the AIDS epidemic, the subject of this stirring documentary about the activists in ACT UP, which helped rally the gay community in a fight toward greater AIDS awareness and prevention—but also “a witness to the plague both as it’s unfolding and as people recalled it.”

To achieve this effect, France shows both ACT UP’s rhetorical strategies and demonstrations, typified by their consummately articulate and well-organized head instigators and public demonstrations, including die-ins outside City Hall in Manhattan and the placement of a giant condom over Jesse Helms’s home.

As a counterpoint, in How to Survive a Plague he reminds us of the limited nature of discourse surrounding AIDS in the 1980s and most of the ’90s. Chillingly, during a Crossfire interview in which ACT UP spokesperson Peter Staley questions why the FDA was not more actively pursuing upwards of 140 experimental drugs as potential cures for AIDS, the two interviewers—inducing Pat Buchanan—counter Staley’s prepared, measured rhetorical questions with barely contained hostility.

That reception was hardly isolated. France shows members of ACT UP fostering “a cultural community, a group of people that were fundamentally connected to one another.” But as activist and playwright Larry Kramer—whose writing and public speaking inspired Plague’s title—argues, continuity is vital when discussing AIDS activism.

This sentiment is especially important when you consider that in recent years, Anthony Fauci, an immunologist and head of the National Institute of Allergy and Infectious Diseases, whom Kramer calls the gay community’s “biggest murderer,” has at last endorsed and adopted treatment policies suggested by ACT UP members.

Fauci has not explained why it took him so long to come around. France jokes that he knew when he interviewed Fauci that he would not be filming Fauci’s “McNamara Moment,” in which Fauci admits that he “knew what he’d done.”

“History knows what he did and didn’t do, and why he did and didn’t do it,” France told me. “You’d like him, just like Jesse Helms or Ronald Reagan or any of the Bushes, to come clean, to recognize for forgiveness for their own crimes and failure. That doesn’t mean it didn’t happen.”

Many of the talking heads here also appear in France’s pieces for many publications, including—way back when—this one. In these, France discusses the possibility of finding sustainable AIDS prevention, as well as what motivates people like the now-deceased Christine Maggiore, an activist who denied the lethality of HIV and even claimed that HIV was not the cause of AIDS. (Maggiore, who publicly made it known that she was HIV-positive, died of pneumonia-like symptoms that could have been prevented had she taken anti-HIV medication.)

Seeing the key ACT UP members (and France subjects) who have survived the epidemic is heartening proof that, to a large extent, ACT UP succeeded. How to Survive a Plague, like France’s writing, it is not so much a conversation-starter as a means of further spurring on a continuing conversation that has already been happening for decades now. Its vision of the past is a means of galvanizing future discussion.

David France is a contributing editor at New York magazine. His writing has been featured in outlets including Newsweek—where he was a senior news editor—Vanity Fair, GQ, and The Village Voice.


Human Rights = Public Health

How great a loss was the death of AIDS researcher Jonathan Mann, killed in the crash of Swissair Flight 111? “I’m convinced that if someone other than Jonathan had been the first director of Global Programme on AIDS, the whole response to the epidemic would have been different,” says Peter Piot, one of the earliest HIV researchers and now director of the United Nations AIDS program. “For example,” he continues, “we may have gotten into a repressive approach, perhaps using quarantine. Because let’s not forget that in the early days there were many calls for that.”

Indeed, notes Newsday reporter Laurie Garrett in her definitive book The Coming Plague, by 1987, 81 countries had passed laws against people with HIV or risk groups, usually homosexuals and prostitutes. In Germany, a federal judge declared it might be necessary to tattoo and quarantine people with the virus. Cuba was already quarantining AIDS patients. Some Muslim states were jailing “promiscuous” people, and Chinese officials denied the existence of homosexuals, drug users, or prostitutes in the People’s Republic. In the U.S., President Reagan’s secretary of education, William Bennett, fought Surgeon General C. Everett Koop’s plans for frank education about HIV prevention, favoring instead compulsory testing of all hospital patients, marriage license applicants, and immigrants. Quarantine loomed as a very real threat.

Amid this gathering storm, Jonathan Mann led public health authorities to perhaps their finest hour. Impeccably dressed in bow ties, yet with the gritty experience of running the first major African HIV research program (which, among many accomplishments, showed that HIV could be spread through heterosexual sex but not through mosquito bites), Mann managed to convene more than 100 national ministers of health together in London. There, as Garrett writes, almost 150 nations signed on to a condom-based, compassionate strategy to slow the spread of AIDS. A few months later, he convinced the World Health Organization to make human rights the core of its anti-HIV stratety. These coups played a crucial role in preventing the wholesale repression of people with the virus.

Mann orchestrated this historic consensus from his new position as director of the World Health Organization’s Global Programme on AIDS. At first, recalls Daniel Tarantola, who joined the fledgling endeavor at the beginning, “the program was himself, a secretary, and one typewriter.” Two years later, Mann had rocketed the budget to almost $100 million. His m.o.: hard work, personal modesty, and an eloquence that was at once fiery and logical. “Back at a time when only a few people were screaming” for a humane and effective response, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, “Jonathan was an unbelievably articulate and passionate voice.” Mathilde Krim, founder of the American Foundation for AIDS Research, adds that Mann persuaded people with “the force of the argument, the morality of behaving a certain way, and the practical usefulness of being ethical and respectful of others. He convinced people.”

Mann’s message: AIDS is a global crisis, in which no person or nation is an island. More important, human rights and public health go hand in hand: “In each society, those people who before HIV/AIDS arrived were marginalized, stigmatized, and discriminated against become those at highest risk of HIV infection… The French have a simple term which says it all: HIV is now becoming a problem mainly for les exclus, the ‘excluded ones’ living at the margin of society.”

Mann, who moved to Harvard after leaving WHO, gave a shattering talk at the world AIDS conference two years ago in Vancouver. That was when protease inhibitors arrived, creating a sense of euphoria in the First World, where the expensive drugs were able to prolong life. But Mann warned that this breakthrough threatened the very solidarity among AIDS advocates that had allowed them to hold back repressive policies. In AIDS, he said, “we all started in the same place: with the same lack of treatment and with the same hopes… The industrialized world, shorn of its technologic armor, was forced into developing prevention and care strategies, to listen and learn from the universally available wealth of human experience and wisdom.” He called for individual efforts, including for people with HIV in wealthy countries to “give the equivalent cost of a week of treatment” to give patients in developing countries basic treatment “or relief of pain.”

In December 1996, Mann married Mary Lou Clements, a world-renowned expert on vaccines who founded the Center for Immunization Research at Johns Hopkins University. Clements-Mann, who early in her career worked in the worldwide effort to eradicate smallpox, has conducted more than 100 clinical trials on vaccines, from influenza to hepatitis. She worked on the recently approved immunization for rotavirus, which causes often fatal diarrhea in children in poor countries. She was also working on several HIV vaccines, as well as the first trial of one for hepatitis C.

The couple’s untimely death, not two years after their wedding, was poignant in intimate ways as well. Fauci dined with the couple a few weeks ago and, he says, “Jon and Mary Lou seemed so happy about their future.”


The Virus Fights Back

GENEVA— At least three separate research teams here at the 12th World AIDS Conference announced that strains of HIV resistant to many drugs, including the powerful protease inhibitors, have been transmitted from one person to another. None of these cases was from New York, but among the nearly 14,000 conference participants was a couple from Manhattan, one of whom recently contracted a highly resistant strain of HIV from the other.

AIDS activist Stephen Gendin took years to become resistant to most HIV drugs, using them one after another as they came on the market, desperate to save his life. But now his partner, Kyle McDowell, is starting out with Gendin’s resistant strain. “This eliminates most treatment,” says McDowell.

Such cases re-emphasize the importance of prevention. But they also point to the implacable logic of HIV, which has killed almost 12 million people, infects another person every five seconds, and now is mutating under the pressure of powerful but not curative drugs. “It’s not surprising at all” that resistant strains have begun to circulate, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Indeed, given the astonishing vigor of this virus, many of the conference’s scientific findings were sobering but not surprising. Among the most important are that HIV continues to replicate even when patients are taking potent medication, and that in the very first days after the virus enters the body, it infiltrates certain long-lived cells that then harbor it for many years. So even if a patient has an ordinary strain of HIV that is vulnerable to the drugs—and even if that patient is among the lucky 10 per cent of infected people who live in a First World country, where the expensive drugs are available—still, says

Fauci, “it will be very difficult to eradicate this virus” from the body.

Yet the AIDS death rate continues to drop all across the developed world, and “I don’t think deaths will go back up,” maintains Bernard Hirschel, the doctor who chaired the conference. Like many researchers, Hirschel and Fauci believe it might not be necessary to eradicate every last virus from a patient’s body. They point to growing evidence that suggests the immune system can control HIV under the right circumstances, and that an AIDS-ravaged immune system can be regenerated with therapy. As David Ho, director of New York’s Aaron Diamond AIDS Research Center, puts it, “Control without eradication is something we might call remission.”

Whether the goal is eradication or remission, the lynchpin of therapy is a cocktail of three or more drugs, often involving a protease inhibitor, that patients must take every day to suppress the virus. But McDowell and Gendin are resistant to at least nine of the 11 currently approved drugs—and possibly to all of them.

Gendin has known for more than a year that he carries a multidrug-resistant strain of HIV. He and McDowell never engaged in the riskiest behavior—having Gendin ejaculate into McDowell during anal intercourse—but sometimes Gendin would enter McDowell without a condom, withdrawing before climax. (In a case documented by San Francisco researchers, the source partner also withdrew before ejaculation; HIV is known to be present in preseminal fluid.) In addition, McDowell was often the insertive partner, and he didn’t use a condom either. This, too, could have led to his infection.

Several studies presented at the conference suggested that some people are relaxing their safer-sex standards because they believe the new treatments have made AIDS manageable. Prevention workers will undoubtedly have to combat this misconception, but McDowell’s story makes it clear that people engage in unprotected sex for reasons that are tangled and personal.

“For 10 years I was so safe,” McDowell explains. His riskiest activity was to fellate without a condom, a practice generally considered low risk, and which he would do only once or twice a year. His friends, he says, considered his standards “maddeningly tight.” Then McDowell turned 30, which, he says, “had a lot to do” with why he’s now infected. He remembers thinking, “Oh my god, I let my twenties go.” So he let himself enjoy “a few stolen insertions” with Gendin. Those gave him morning-after anxiety, but twice over a one-year period he tested HIV-negative, which bolstered what turned out to be a false sense of security.

Having sex without a condom “really made me feel profoundly erotically close,” McDowell recalls. “When Stephen was not feeling well, it seemed the only way to be intimate.” And when problems arose in the relationship, McDowell says, “I wanted to fix it with something highly symbolic.” So they would have “makeup sex” that sometimes became “really intense.” There was, he says, “something profoundly rich about risking my life for Stephen.”

“This notion of sharing everything is being romanticized, and that’s dangerous,” warns Martin Delaney, a leading AIDS activist. Indeed, many activists believe Gendin had already romanticized “barebacking,” as unprotected sex is called, when he wrote an article in the AIDS magazine POZ last summer about having skin-to-skin intercourse with another man who was also HIV-positive. That article sparked a heated controversy, because even between two infected people, a drug-resistant strain might be transmitted, unleashing a secondary infection that could sabotage a drug regimen. But many people with HIV consider that possibility theoretical.

Of course, there is no doubt about the danger to an HIV-negative partner. “So why was I doing something risky?” Gendin asks. “I don’t know. If someone handed me a knife, I wouldn’t throw it around.” Now he feels “guilty and confused.”

Researchers feel worried.

  • In San Francisco, one out of 35 newly infected patients was found to have a virus resistant to all four approved protease inhibitors and most of the AZT family of drugs.
  • In Switzerland, two out of 67 recently infected patients were found to be carrying strains highly resistant to protease inhibitors, and several more were resistant to other drugs.
  • U.S. military researchers found two out of 16 untreated patients with mutations that confer resistance to protease inhibitors.There are likely to be more such cases, if only because more than 40 per cent of U.S. patients are being prescribed substandard drug combinations, which greatly increases the risk of resistance. Moreover, 30 to 50 per cent of all patients have trouble taking their medicine as directed, which also induces resistance.

    Even so, Fauci, Ho, and Frederick Hecht, the lead researcher in the San Francisco case, all warn against exaggerating the danger. It’s likely that “most new infections are coming from people who don’t know they’re infected and haven’t been treated,” says Martin Markowitz of the Aaron Diamond Center, who has been studying recently infected patients for three years. And such individuals are unlikely to carry drug-resistant virus.

    AZT, the first approved AIDS medication, has been on the market for a full decade, yet only about 16 per cent of HIV-positive people in San Francisco start out with a strain that is resistant to that drug. Helene Gayle, director of the AIDS program at the Centers for Disease Control, says that the proportion of people newly infected with strains resistant to protease inhibitors will likely rise only to “the single digits or teens.” But, she notes, for a deadly disease like AIDS that would still constitute “a real disaster,” because those unlucky patients would effectively be thrust back to an era when doctors had few or no options for treatment. Indeed, the San Francisco case was discovered partly because the patient did not respond well to his drugs.

    HIV doesn’t need to be super-resistant to wreak havoc. Ordinary HIV is virulent enough. In the first days after infection, the virus infiltrates so-called “resting T-cells.” Since those cells are long-lived, HIV can lurk in them for years, dormant but capable of re-emerging and continuing the progression toward AIDS. If drugs could completely shut off virus replication, then this pool of cells would die off in an estimated three to five years.

    But last year, evidence emerged from Fauci’s lab that the drugs don’t completely suppress the virus. And in Geneva, Ho presented proof that HIV keeps replicating even when the drugs appear to be working so well that very sensitive tests cannot detect any virus in the blood. HIV’s under-the-radar replication keeps infecting the resting T-cells, foiling attempts to eradicate the virus. Ho’s conclusion: “We have overestimated the potency of our [medical] regimens.”

    Trial results of several promising new drugs were reported, but it remains to be seen if they will have a more powerful effect. Probably the most encouraging was a drug called efavirenz (brand name Sustiva), made by DuPont. It was shown to be at least as potent as the strongest protease inhibitor, though its long-term efficacy is not yet known. In marked contrast to the corporate PR, Paul Friedman, the scientist who led the discovery and development of efavirenz, was humble: “This virus,” he says, “is very, very difficult.”

    Indeed, Ho’s work suggests that even under the most intense drug pressure, HIV not only keeps replicating, it also mutates and evolves. But when he charted the changes in HIV’s genes, he didn’t see any evidence of evolution toward drug resistance. So, he reasons, “there must be some compartment where virus can grow without any selective pressure for drug resistance.” This sanctuary might be an anatomical organ, or it could be certain kinds of cells present in different organs. Ho’s finding could be a fluke due to his small sample size—he studied only seven patients. But Emilio Emini, who heads pharmaceutical giant Merck’s AIDS effort, says that “slow evolution of resistance mutations” has occurred in patients on apparently effective drug regimens. He thinks that explains some cases in which the drugs appear to be working perfectly, yet the virus eventually breaks through, rising back up to dangerous levels.

    Whether this ongoing replication maintains HIV in the body or actually leads to drug resistance, Ho suggests intensifying therapy, and, indeed, some doctors are recommending that their patients take four drugs instead of three. But the drugs often cause side effects. Widely publicized have been fat and cholesterol disturbances, possibly leading to coronary problems in the most severe cases. So other doctors are taking the opposite approach and suggesting that their patients delay starting therapy if they are healthy and have relatively intact immune systems.

    Their logic was vividly illustrated in a plenary speech by activist Mark Harrington of Treatment Action Group, or TAG. Harrington recounted his personal history of HIV and showed slides of his lymph nodes, a key immune-system site. Just after the last international AIDS conference two years ago, HIV had ravaged Harrington’s lymph nodes, which literally looked tattered on the slide. His CD4 cell count, a common measure of immune function, had plummeted to 152; healthy people typically have more than 1000. But now, following two years of effective therapy, Harrington’s CD4 count has soared to 925 and he has “nice, plump, healthy” lymph nodes. “I’m lucky I waited” to begin therapy, Harrington said. “I could be dead if I had listened to those same researchers who now say hit hard and hit early.”

    But Fauci draws draws a different lesson from Harrington’s experience: Harrington was lucky not because he waited until he lay at death’s door to start treatment, but rather because effective drugs were finally developed. Fauci suggests that anyone who has a high degree of virus replication, even those who are very healthy, should start therapy, because suppressing the virus can protect the immune system. The cold fact is that no one knows the optimal moment to start therapy.

    PERHAPS THE BEST NEWS from Geneva is that most patients who respond well to treatment are slowly regaining their immune systems. Brigitte Autran, a leading immunologist from France, has studied more than 300 patients who were fairly advanced in HIV disease. Among those who responded well to the drugs and almost never missed a dose, CD4 counts have risen steadily “with no plateau,” says Autran. She looked at many other aspects of the immune system, such as the ability of cells to respond to various bacteria and viruses, and in virtually every test the immune system showed steady improvement.

    Autran thinks “there is no limitation” to the capacity of the immune system to revive itself, though she estimates that full recovery will take four to eight years. That process might be speeded up by special immune-enhancing drugs, such as interleukin 2, or IL2, which showed excellent results in several studies presented at the conference. But even with IL2, the immune responses specific to HIV almost never come back.

    The human immune system is exquisitely precise; the cells and antibodies that protect against the flu, for example, do nothing against herpes or TB. The reason HIV is so devastating is that it kills the very immune-system cells that orchestrate the body’s counterattack against it. These cells are called HIV-specific helper T-cells, and the virus wipes them out in just three to 18 months after it has entered the body. Unfortunately, Autran has seen no revival of HIV-specific helper cells, even after two years of immune recovery. (The only researcher who has seen such recovery in advanced patients is Franco Lori, who has seen it in six of 12 patients treated with the AIDS drug ddI and an experimental drug called hydroxyurea.) But to control HIV and achieve what Ho calls remission, HIV-specific immune responses are required.

    A few patients—less than 1 per cent—control the virus on their own, without ever taking drugs, and many of these “long-term nonprogressors” have very strong HIV-specific responses. Furthermore, Harvard’s Bruce Walker and the University of Seattle’s Julie McElrath have each found that if patients are treated very early, within weeks of getting infected, suppressing the virus prevents the destruction of the critical HIV-specific helper cells. Encouraged by anecdotal cases of patients who went off their medication yet have been controlling HIV without drugs, Walker and Hirschel are each planning trials to see if that experience can be duplicated. In the meantime, doctors strongly warn patients against stopping their drugs, lest HIV come roaring back.

    The trials by Hirschel and Walker will use patients who started therapy soon after being infected. But the vast majority of people with HIV don’t know they are infected until long after they have lost their HIV-specific responses. Can anything be done for them? Perhaps. In a “late-breaker” study, New York University Medical Center’s Fred Valentine showed that an HIV vaccine developed by the late Jonas Salk stimulates strong HIV-specific helper responses in midstage patients being treated with combination therapy. Patients who did not get the vaccine but did receive standard treatment showed no such gain.

    In the future, then, it is possible that patients will be treated with standard drug cocktails to suppress their virus, plus IL2 to hasten recovery of their immune systems, plus an AIDS vaccine to stimulate their HIV-specific immunity. After all that, maybe, just maybe, some patients would be able to stop taking the toxic and demanding drug cocktails and have their immune system control the virus on its own. But even if that goal isn’t achieved, invigorating the immune system might extend the effectiveness of drugs, buying patients the most valuable thing: time.Research assistance: Tyler Schnoebelen