The AIDS epidemic is far from over. It’s not even under control. “The worldwide situation is deteriorating,” says Dr. Jonathan Mann, former director of the World Health Organization’s Global Program on AIDS. “We are facing a decade in the 1990s that will be far more difficult than anything we saw in the 1980s.” The WHO estimates that as of this year 700,000 people have developed AIDS worldwide and 6 million to 8 million have contracted the virus that causes it. By the end of the decade, an estimated 5 million to 6 million will be sick, and the total number infected may approach 20 million. Worse still, the situation isn’t expected to stabilize for several more decades.
Already, the AIDS virus infects a third of the population in some parts of Africa. This nation’s most desperate neighborhoods appear headed in the same direction. Regional surveys have turned up infection rates of 5 to 12 percent among pregnant women in the Bronx, 25 percent among young men surveyed in Newark, N.J. But the poor aren’t the only ones suffering. Dr. June Osborn, chairman of the National Commission on AIDS, foresees a time when most Americans may know someone with AIDS. “By the end of the 1990s,” she says, “people will be shaking their fists and saying, “Why didn’t you tell us?’ That’s going to hurt, because we did.”
This week thousands of people from throughout the world will converge on San Francisco for the Sixth International Conference on AIDS (page 24). What once served as a quiet forum for sharing technical insights will look more like a political convention, as the affected segments of society–not just scientists but patients and caregivers, public officials and angry activists–unfurl their flags. No longer just a medical problem, AIDS has become a pock on the social order, a festering emblem of countless other ills. Federal spending for AIDS research and treatment has climbed to $1.6 billion in just nine years. Scientific progress has been brisk. Yet for many of the afflicted, here and throughout the world, minimal health care is still a distant hope.
Though AIDS is spread solely through the exchange of blood or other body fluids, local conditions have a lot to do with who gets sick and how. In Africa. the virus is transmitted almost exclusively through heterosexual contact. In Thailand–where the number of infected people has shot from 1,000 to roughly 50,000 in just three years–the epidemic apparently started among intravenous drug users and spread into the heterosexual community. In Eastern Europe, AIDS has been spreading mainly through unsafe medical practices.
The U.S. epidemic has always been concentrated in major cities, among gay men and IV drug users. But that pattern is changing as the epidemic matures. Last year AIDS incidence rose nearly four times as fast in the nation’s smallest cities as in its largest ones. And while the number of new cases rose by 11 percent among gay males, it increased by 36 percent or more among heterosexuals and newborns. By the year 2000, says Dr. James Chin, an epidemiologist in charge of AIDS surveillance at the WHO, “heterosexual transmission will predominate in most industrial countries.” The growth of the epidemic may be slower among heterosexuals than it has been among gays or IV drug users, but it will be implacable nonetheless. “AIDS is a sexually transmitted disease,” says Dr. Robert Redfield of the Walter Reed Army Medical Center, “and the fact is that most of us in society are heterosexual.”
Monogamous couples are not at risk, but there’s no evidence that Americans are about to become wholly monogamous. Syphilis and gonorrhea–diseases that not only indicate unsafe sexual practices but facilitate the spread of the AIDS virus–have skyrocketed in recent years. At the same time, the crack epidemic has created a whole new class of high-risk heterosexuals: women who trade sex directly for the drug. “We’ve seen the rate of syphilis in various parts of the country quadruple because of sex associated with crack,” says Don Des Jarlais of the Chemical Dependency Institute at New York’s Beth Israel Hospital. “The same thing could happen with AIDS. "
With or without crack, American teen-agers are ripe targets for AIDS: they’re already experiencing 2.5 million cases of sexually transmitted disease every year, and nearly a million unintended pregnancies. “We know their sexual behavior results in significant risk for infection,” says Dr. Gary Noble of the federal Centers for Disease Control. Indeed, at least 20 percent of today’s AIDS patients were probably infected as teens.
As long as we fail at sex education and drug-abuse treatment, millions of Americans will remain at risk. And clearly we are failing. Medically, though, the past decade has brought remarkable successes. No one had heard of AIDS when doctors started describing the syndrome in 1981. Since then, scientists have not only identified the human immunodeficiency virus (HIV) but learned a great deal about how it infects cells and ruins the immune system. The 1980s brought a diagnostic test, a safe blood supply and several useful treatments. Thanks to drugs like AZT and pentamidine, patients who would once have died within months of developing AIDS are now surviving a year or more.
In the short run, treating the myriad infections and cancers that actually kill AIDS patients is the surest way to extend their lives. Activists have long accused scientists, drug companies and federal agencies of neglecting these secondary complications, of preferring the higher drama of fighting the virus itself. The criticism has had an effect. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), says the proportion of federally funded AIDS studies relating to opportunistic infections has risen from 10 to 20 percent during the past year and may eventually grow to 30 or 40 percent. Yet treating symptoms won’t solve the problem. AIDS patients who survive early bouts with pneumocystis carinii pneumonia and other once lethal infections are now falling prey to an array of other maladies. Among San Francisco AIDS patients, the number of lymphomas rose by 48 percent in 1987 alone. Until the AIDS virus can be locked out of the body, or paralyzed from within, the plague will spread and the afflicted will die.
The epidemic has prompted a resurgence in the study of infectious disease. Antiviral drug research, long stagnant before AIDS struck, is now among the hottest fields in medicine. And the quest for a vaccine, though far from fruition, is proceeding briskly. Can this virus be stopped? What are the strategies? What are the obstacles? These turn out not to be simple questions, for the battle against AIDS is being fought inside the cell, amid genes and proteins and enzymes and antibodies. But the questions are worth grappling with. All of humanity has a stake in the answers.
Just nine years ago, epidemic diseases were a thing of the past. Modern medicine, having subdued The Germ with vaccines and antibiotics, was busy saving us all from cancer and heart disease. Then came AIDS, and the realization that a devious bug could still cause a worldwide plague. At first no one knew what was causing the mysterious illness, but scientists in Paris and Washington soon linked it to an infectious agent known as a retrovirus. Today there are still unanswered questions about the human immunodeficiency virus, such as why it causes illness so much faster in some people than in others. But its basic mechanisms are now well understood.
HIV has no life of its own. Unlike a bacterium, it doesn’t absorb nutrients, generate waste or reproduce by dividing. It’s just a protein capsule containing two short strands of genetic material (RNA) and a few enzymes. It happens to use human cells to perpetuate itself. After infecting someone, HIV may spend 10 years or more quietly ensconced within various tissues and organs. But when activated, it turns certain immune cells into virus factories, which produce a flurry of new virus capsules and die. Other cells become infected in the process, and the immune system falls like a house of cards.
The immune system is an elaborate, internal defense network that includes different types of blood cells. Among these immune cells, the ones that identify an intruder and authorize an attack on it are called T4 lymphocytes, or (imprecisely) “helper T cells.” Every T4 cell has appendages called CD4 receptors, through which it exchanges information with other immune cells. And it is through these CD4 receptors that HIV attacks. The outer shell of the HIV capsule (known as the envelope) is equipped with an appendage called gp120. This distinctive protein molecule happens to fit the CD4 receptor as a plug fits a socket. When the two molecules dock, the contents of the viral capsule–the RNA and the enzymes flow freely into the cell’s interior.
Once inside, HIV becomes a permanent feature of the cell. First, an enzyme called reverse transcriptase uses information encoded in the RNA to manufacture a double strand of DNA–a piece of software that can direct the cell to manufacture more virus. This DNA, known as the provirus, then integrates itself into the host cell’s chromosomes. It represents just a tiny segment of the cell’s genetic code. Once activated, however, it’s the only segment that counts.
The trouble begins when the provirus starts directing enzymes in the host cell to produce new strands of viral RNA. These rogue pieces of RNA serve as a blueprint from which other enzymes start churning out the raw material for new virus capsules. These raw materials (long protein molecules) get chopped into shorter pieces by an enzyme called protease. Those pieces then clip together to form new HIV particles, which burst from the surface of the host cell and float off to infect others. The host cell is killed in the process.
One reason HIV poses such a challenge is that the infection itself is not even theoretically curable: modern biologists, for all their ingenuity, are far from knowing how to purge unwanted DNA sequences from human chromosomes. Still, scientists are hopeful that by keeping the virus from replicating so wildly, they will gradually make it less deadly. Scores of researchers are working on drugs to interfere with HIV’s production cycle at one stage or another. Twenty-one such drugs are now under development in this country alone. The hope is that they’ll work, in some felicitous blend, to make AIDS a chronic, manageable condition, much like diabetes or high blood pressure.
So far, only one of these drugs has been approved as a treatment for AIDS. Zidovudine, or AZT, attacks the virus after it has wormed its way into the cell but before it has integrated itself into the host cell’s chromosomes. Specifically, it impedes the “reverse transcription” of viral RNA into DNA. The only way HIV’s reverse transcriptase enzyme can manufacture DNA is by gathering up chemical units called nucleosides and matching them to the pattern on the viral RNA. AZT looks just like one of these nucleosides. In fact, reverse transcriptase prefers it to the real thing. But AZT turns out to have a slightly different structure. When it’s clipped on to a growing chain of DNA, the next link doesn’t fit and the whole production is foiled.
Conceived as a cancer treatment back in the 1960s, AZT found no use until 1986. It now earns the Burroughs Wellcome Co. well over $100 million a year. The big comeback started when scientists noted a decline in infection and death among AIDS patients taking a daily dose of 1,200 milligrams. Despite a number of side effects-ranging from headached vomiting and malaise to bone-marrow suppression and anemia–AZT sped through the drug- approval process in record time. In March 1987, the Food and Drug Administration approved it as a treatment for patients with symptoms of AIDS or with T4 counts below 200 (the normal range is 600 to 1,200). Since then, AZT has been found to work just as well at half the original dose, and federal guidelines have been changed to recommend the drug for any infected person whose T4 count dips below 500–even if no sickness has set in
That may sound like a minor adjustment, but it pushes the number of potential AZT users in this country from 40,000 to more than 600,000. A panel convened by the National Institutes of Health made the early-treatment recommendation this spring, after two studies showed that AZT could delay the initial appearance of AIDS. But many experts consider the move premature and potentially dangerous. They note that several ongoing studies have so far failed to show the same beneficial effect. Moreover, they say, the NIH studies didn’t compare the advantages of early and late treatment. They compared early treatment with no treatment. “We don’t know that it ultimately does you any good to delay crossing the 200 mark by a few months,” says Dr. John Hamilton, chief of infectious diseases at the Durham, N.C., VA Medical Center and cochair of an AZT trial designed to answer that question. “If you’re: building up resistance to AZT by taking it early, when you’re still feeling fine, you may be losing a crutch you could use later.”
Even the proponents of early treatment agree that AZT leaves much to be desired. First, it, quite toxic: even with lower doses, nearly a third of those taking the drug develop grave bone-marrow problems within a year. Second, it’s not cheap. Burroughs Wellcome has twice reduced the price but still charges $1.20 for every 100-mg capsule–more than $200 for a month’s supply. Third, while it does help ward off opportunistic infections in AIDS patients, it doesn’t prevent the outbreak of lymphomas or tumors such as Kaposi’s sarcoma: Most important, it seems to become less effective as the virus mutates out of its range of action.
Researchers are hopeful that AZT’s close relatives DDI and DDC, both now in clinical trials, will help address some of these problems. DDI and, especially, DDC are toxic in their own right: both cause a painful nerve irritation called peripheral neuropathy, and DDI can damage the pancreas. But they could provide alternatives for people who can’t tolerate AZT or who develop resistance to it. Both drugs are also being tested in low-dose combinations with AZT. The hope is that patients will get cumulative benefits but, because of the lower doses, experience less toxicity and resistance “The way to go,” says Dr. Samuel Broder, head of the National Cancer Institute, “is not to discard drugs that show promise, even with side effects, but to find ways to use them more creatively.”
AZT and its kin all attack HIV at the second stage of its life cycle–after it has entered the host cell but before it has integrated itself into the cell’s DNA. But there are several other possibilities. One is to keep the virus from entering the cell in the first place. To do that, one would have to keep HIV from plugging its distinctive appendage–the gp120 envelope protein–into the CD4 receptors on target cells. Several laboratories have designed synthetic, free-floating CD4 receptors with just that thought in mind. In principle, flooding the blood with this “soluble CD4” should inactivate the virus by covering all its plugs before they find real sockets. That’s exactly what happens in a test tube. There is no evidence yet on whether soluble CD4 will help infected people, but toxicity tests have shown no serious side effects. In an interesting variation on this same approach, the Upjohn Co. and others are now working on molecules that combine CD4 and a potent synthetic toxin. When the CD4 binds to the viral envelope proteins protruding from infected T4 cells, it’s supposed to release the poison and kill them. Unfortunately, there is at least one large drawback to the whole CD4 approach. The molecule is very expensive to make, and it breaks down so fast that it has to be taken–by injection–every few hours.
Suppose the virus eludes both CD4 and AZT, penetrating the cell and infiltrating the local DNA. There are still possibilities for checking its growth. Opportunity No. 3 arises shortly after the provirus (the integrated viral DNA) starts running off RNA copies of itself. The enzymes that manufacture the raw materials for new virus particles from this RNA use its chemical sequence as a blueprint. If the enzymes can’t read the blueprint, they can’t do their work. And it’s possible–using genetically engineered “antisense” molecules–to make the blueprint illegible. By zipping itself onto a crucial segment of the viral RNA, an antisense molecule blots out vital information, and protein production grinds to a halt.
Antisense represents a whole new approach to drug design, and HIV is not its only potential target. Traditionally, notes biochemist Jack Cohen of Georgetown University Laboratories, researchers have treated people with various organic compounds in the hope that one would prove therapeutic. With antisense, he says, “you figure out exactly what genetic process you need to alter and design a molecule accordingly. " In test-tube experiments, antisense molecules have slowed production of the AIDS virus by 90 percent. The catch is that they’re still difficult–and exceedingly expensive–to make. “We’ve been working on [an antisense drug] for a year, " says Dr. Jeffrey Laurence of the Laboratory for AIDS Virus Research at Cornell University Medical College. “I’m promised that by the end of the summer we’ll have enough to treat one mouse. "
While awaiting affordable antisense, researchers are targeting still later stages in the viral life cycle. A fourth possible strategy is to keep HIV’s protease enzyme from milling the construction materials into pieces that can form new virus particles. A number of companies have developed drugs that work at this stage, and human trials are expected to start within the next year. These “protease inhibitors” have performed well in test-tube experiments, and animal tests have turned up no serious side effects. That’s not surprising. For unlike AZT and its kin, which disrupt a number of cellular processes the protease inhibitors affect only a single enzyme. As a result, researchers expect them to be far less toxic.
In other labs, scientists are working with a fifth group of antiviral agents, known as These are antiviral chemicals produced naturally by cells. Drugs that step up production of interferons can help control the growth of tumors–and at high doses, the same drugs seem to impede the budding of new virus particles from infected cells. In a study published this month, NIH researchers conclude that alpha interferon can have a “significant antiviral effect” in patients whose immune systems are still largely intact. In a small trial involving asymptomatic patients, the investigators found that 41 percent of those getting the drug became “culture negative,” meaning the virus dropped temporarily out of sight in their blood samples. Only 13 percent of the untreated subjects became culture negative (a common but temporary occurrence). Moreover, T4 counts held steady in the treated patients but declined slightly in the others. There is a catch, of course: the treatment was so toxic that a third of those receiving it dropped out of the trial.
Antiviral drugs aren’t the only hope for eliminating AIDS. If we could vaccinate everyone, the epidemic might really be stopped. Vaccines have triumphed famously over other viral diseases, from measles to smallpox to polio. The approach consists of exposing people to a virus in some harmless form to provoke a natural immune response without causing serious illness. Unfortunately the AIDS virus is well designed to foil that approach. One problem is that no one knows what natural immunity would consist of. Infected people produce a flurry of antibodies directed at different parts of the virus, but those people don’t end up safe from future infection. They end up dead, as the virus destroys the system producing the antibodies. It’s possible that one or more of those antibodies would prevent infection in healthy people,but there’s no guarantee. A second problem is that HIV is not a single, well identified target. Like a cold virus, it varies widely and changes fast. There are dozens of strains of HIV, and a vaccine that worked against one might prove worthless against another.
Despite these and other obstacles, the quest for a vaccine is gaining momentum. “A year ago I wouldn’t have been able to say whether we would ever have a vaccine,” says Fauci, of the NIAID. “I think most scientists are now reasonably optimistic that some time, hopefully in the 1990s, we will.” The change of heart stems from a handful of recent experiments. Two research teams have succeeded at protecting monkeys from SIV (the simian AIDS virus), and two other groups have protected chimpanzees from HIV itself. Still other scientists have shown that infected women who produce large amounts of a particular antibody are less likely to bear infected children–a finding that could lead directly to a prenatal vaccine.
In the monkey trials, conducted at primate-research centers in Massachusetts and Louisiana, scientists injected animals with whole, inactivated SIV to produce an immune response and then challenged them with unadulterated virus to see what would happen. The New England researchers managed to protect two out of six monkeys from infection, the Louisiana group eight out of nine.
The chimpanzee experiments involved a different approach. Researchers at two biotechnology companies–Pasteur-Vaccines in Paris and Genentech in South San Francisco–inoculated their animals with “subunits” of the human AIDS virus before injecting them with the whole agent. (HIV infects chimps but doesn’t cause illness.) In the Pasteur experiments, two chimps resisted infection after receiving cocktails of several HIV fragments. The Genentech vaccine, based on a fragment of HIV’s gpl20 envelope protein, also protected both of the chimps that received it.
However impressive, none of these feats means that school kids will soon be lining up for inoculations against AIDS. To be of real use, a preventive AIDS vaccine would need to have a lasting effect against a wide range of virus strains. The animals in these experiments were tested at the peak of their immune responses, and they received the same strains of virus they had encountered in their vaccines. “If we had a simple vaccine that worked in chimps,” says Marc Girard, the virologist who directed the French experiments, “it would be five years before it could be used in man, with toxicity tests and all that. And we’re very far far from that takeoff point.” Even a vaccine that proved effective in chimps might perform miserably in people. And finding out would be a challenge in itself, since human subjects can’t be purposely exposed.
One virtue of trying to block mother-to-child transmission is that success is easier to gauge. Since 30 to 40 percent of the children born to infected women are themselves HIV positive, a vaccine that changed that ratio would clearly be making a difference. No one has yet tested such an agent, but Dr. Arye Rubinstein, director of the Center for AIDS Research at New York’s Albert Einstein College of Medicine, is rapidly laying the groundwork.
Intrigued by the fact that many infected mothers don’t bear infected children, Rubinstein and his colleagues set out to identify specific antibodies that might set those women apart. Last month, in a study of 15 AIDS pregnancies, the researchers described such an antibody. Of the 11 women in the study who bore infected babies, not one was producing an antibody directed at the HIV envelope protein’s so-called principal neutralizing domain (PND), a short molecular segment that is common to many different strains of the virus. By contrast, the PND antibody was present in three of the four mothers who bore healthy babies. “We suspect the fourth mother had the antibody,” Rubinstein says, “because it showed up in the baby.”
The PND antibody doesn’t seem to help people once they’re infected; the mothers who produce it suffer the same fate as those who don’t. But if that antibody is the reason some babies are born uninfected, then protecting others might be fairly simple: you would simply inoculate mothers with the tiny piece of the virus that engenders it. Dr. Yair Devash of Ortho Diagnostics has already fabricated the viral fragment, and Rubinstein has incorporated it into a vaccine that could be given to pregnant patients. He’s now testing it for toxicity in animals and expects to start a human trial later this year. If the vaccine were to succeed at protecting babies, he notes, it might protect other uninfected people as well.
Preventing infection is not the only goal of vaccine research. Scientists are also testing vaccinelike agents designed to boost the defenses of people who are already infected. These researchers study the body’s production of antibodies to different parts of HIV, then try to amplify the most useful responses. Several preliminary studies show promise. Dr. Robert Redfield of the Walter Reed Army Medical Center has observed that when some patients are exposed to a synthetic fragment of gpl60 (a large envelope protein that includes gpl20), they produce antibodies directed specifically at that fragment and their T4 cells die less quickly. Allan Goldstein of George Washington University has sparked potentially useful immune activity by exposing people to a piece of the virus core. And Jonas Salk, inventor of the polio vaccine, has reported beneficial effects in about half of the patients he has treated with whole virus stripped of its envelope.
Again, because HIV can hide in places that are beyond the reach of the immune system, none of these therapeutic vaccines could root out the infection completely. But as Salk observed recently, winning and losing are not the only alternatives in the battle against AIDS. A negotiated settlement may still be possible.
AIDS, unfortunately, is not just a medical challenge. Science will eventually produce better treatments, maybe even a vaccine. The question is whether these costly advances will reach the populations most in need. It’s clear that the burden of sick people will rise steeply during the 1990s, but not at all clear that the world’s health systems are prepared to respond. “My fear,” says Dr. Ruth Osborn, of the National Commission on AIDS, “is that [scientific progress] will be overwhelmed by a health-care disaster.”
All over the world, the epidemic is raging most fiercely within groups that are most removed from education and health care. One major exception is the U.S. gay population. Since the epidemic began, homosexual men have fought discrimination, demanded treatment and research, and reaped the rewards of safe sex and blood testing. In large groups that have been followed over the past decade, the proportion becoming infected each year (not developing AIDS but contracting the virus) has fallen from 7.5 percent in the early 1980s to 1 or 2 percent today. Studies also suggest that infected gay men are living longer thanks to AZT and new treatments for secondary infections.
The experience of inner-city minorities could hardly be more different. Infection rates have not declined substantially among intravenous drug users. And as the epidemic spreads to their sex partners and children, new treatments are making little difference. “These people are intensely poor, alienated, powerless,” says Dr. Harold Freeman of Columbia University and Harlem Hospital. Last fall Freeman coauthored a study showing that black men in Harlem were less likely to reach 65 than men in Bangladesh. The data were collected before AIDS even struck. “This is a disaster on top of a disaster,” he says. “The people who are suffering need to cry out. But the people involved in this problem have no voice.”
Minority women who are infected by their partners may avoid seeking treatment for fear they will lose their children to foster homes if their illness is discovered. Maria, a 31-year-old Hispanic woman in Chicago, is the widow of the man who infected her after contracting the virus through his own drug use. Now, with three children to care for (one of them HIV positive), she is suffering full-blown AIDS. Yet she and her family keep her illness a secret. They fear that if others knew, the children would be excluded from school and they from their jobs and their church congregation. Maria’s family curandera, a traditional healer who treats patients with herbs, incantations and prayer believes persistent illness is a sign that the sufferer has strayed too far from Latino culture and is being punished by God.
Inner cities aren’t the only places health care is lagging. Consider rural Georgia, where AIDS rates have soared in recent years. None of the 14 hospitals in the Southeast Health Unit, a 16-county area roughly the size of Massachusetts, can afford to buy the $8O,000 machine needed to test patients’ T4 counts. “The problem is real critical now,” says Dr. Ted Holloway, director of the Southeast Health Unit. “There is a limited amount of AZT that we can give to indigent patients, but we have to have a T-cell count.” The problem is compounded by a lack of physicians willing to treat the disease. “No one wants to be the AIDS doctor,” says Halloway. “If you set up a service, people are going to come from miles away.”
Because people who are infected with HIV can’t buy private insurance, Medicaid has become a major source of care. Roughly 40 percent of AIDS patients end up on Medicaid, and the federal portion of AIDS-related Medicaid spending has soared from $10 million in 1983 to an anticipated $670 million this year. Yet many infected people who need the assistance don’t qualify: besides being poor, one has to be over 65 or a member of a family with dependent children or totally disabled. For many people, that means no medical care until total disability sets in. When AIDS patients finally do qualify for Medicaid, they’re often hospitalized for illnesses that might have been prevented through earlier intervention.
To eliminate the Catch-22, Congress is now considering legislation that would let states approve outpatient services for infected people as soon as treatment is needed to prevent a decline in health. And the House and Senate have recently passed bills that, if signed into law, would provide an additional $600 million to $700 million for AIDS care each year. To Ruth Osborn, head of the National Commission on AIDS, such efforts are mere “fingers in the dike.” This spring the federally appointed commission issued a report to the president, decrying a lack of leadership from the federal government and repeating its demand for a national AIDS plan with clear roles for federal agencies, state governments and the private sector. To date the report has elicited a pro forma letter of appreciation.
No single government initiative is going to solve the AIDS crisis. The crisis is global, and it is magnifying social problems that were already enormous. But complacency would be a mistake. Jonathan Mann, the former WHO official, argues that the world has actually been lucky with the AIDS epidemic so far. Had the virus had a longer latency, the disease might just now be coming to light, in a much greater number of people. The next such virus–and there will most assuredly be others–may be more devious than this one. What HIV teaches us about retroviruses, and about the necessity of education and basic health care for all, could turn out to be valuable. “It takes a lot of hubris to imagine that this couldn’t happen again,” says Mann. “It could be happening right now.”
Most of the 1 million infected in the United States will be sick by 2000; worldwide, six times that many.
Most AIDS patients are still gay men and IV drug users. But the rate of increase among heterosexuals and newborns proves that the virus knows no boundaries. Number of AIDS Percent Increase Cases 1989 1988-1989 Gay or bisexual men 19,652 11% IV drug users 7,970 20% Heterosexuals 1,562 36% Newborns 547 38%
The AIDS virus turns cells into factories that produce more viruses. New drugs show hope of bringing the process under control.
Soluble CD4: May keep the virus from penetrating a target cell.
AZT: Blocks the production of viral DNA.
Antisense: Blocks the production of new viral material.
Protease Inhibitors: Keep new viral material from assuming mature form. Interferon: May keep newly assembled virus particles from leaving host cell.
The viral production cycle involves six basic steps. (1 ) The virus attaches to receptors on a host cell, injecting pieces of genetic material (RNA) and enzymes. (2) A viral enzyme transcribes the RNA into the same form as the host cell’s genetic material (DNA). (3) The viral DNA is integrated into the chromosomes in the nucleus of the host cell. This integrated DNA is called provirus.
(4) After a long, idle period, the provirus directs enzymes in the host cell to produce new strands of viral RNA. The new viral RNA serves as a blueprint. Other enzymes use it to produce proteins that will become new virus capsules. (5) An enzyme called protease cuts the long, unmilled proteins into shorter pieces, which clip together to form new capsules. (6) The completed capsules bud from the surface of the cell.
The Sixth International Aids Conference convening June 20 in San Francisco will, as usual, devote itself mostly to medical issues. But this year medicine may be upstaged by activities of a decidedly unscientific nature. For one thing, this also happens to be the week of the annual Lesbian and Gay Freedom Day Parade, which stirs gay pride and will likely attract more than 200,000 spectators. And demonstrators, including the militant ACT UP (AIDS Coalition to Unleash Power), are expected to disrupt proceedings throughout the five-day conference; the most dramatic protest could come during a speech by Health Secretary Louis Sullivan on June 24. This will also be the first AIDS conference to be boycotted: more than 100 organizations, including the International Red Cross, are staying away to protest a controversial U.S. immigration law barring foreigners with HIV infection from American shores- even though Washington has created special 10-day visas for conference participants.
Meanwhile, the scientific quality of the meetings is expected to be higher than in past years, with only half of 4,900 submitted research abstracts accepted for presentation. (Last year eight were rejected.) Yet despite a number of papers devoted promising new vaccines, no bombshells are expected. A rundown of the main inside and outside events:
Several dozen conference papers will address new therapies showing mixed results in clinical trials. They include the controversial antiviral drug, Compound Q, and lentinan, a mushroom extract that may boost the immune system by raising the CD4 cell count.
A Canadian researcher will report on adverse effects of nonoxynol 9–a contraceptive jelly once believed to afford protection against HIV infection.
There will be many papers on AIDS in women and children, with one San Francisco study revealing that children of infected mothers who are born free of the HIV virus nevertheless suffer from developmental problems.
Researchers will discuss new findings on sexual attitudes in the AIDS era. One study will show that after four years, 19 percent of gay men relapse into risky sex practices.
Researchers monitoring the rate of heterosexual transmission of the AIDS virus in the United States will discuss a study showing that less than 2 percent of all men are infected by female partners, while 20 percent of women are infected by their male partners.
There will be four times more abstracts from the Soviet Union and Eastern Europe than in the past-including a report about the transmission of HIV from an infected baby to its mother through breast-feeding.
All the above is apt to be played out against some of the liveliest street theater yet seen at an AIDS conference. The estimated 10,000 participants-plus 2,000 journalists, including at least one network anchorman-will make it the biggest AIDS gathering ever.
