Ever since it was announced at a 1984 press conference that HIV was the cause of the immune-system mayhem known as AIDS, seers have periodically predicted that the end of the epidemic was near. But the trumpets have grown louder in recent weeks, as the success of the "triple-combo therapy" of protease inhibitors, AZT, and 3TC has been recorded.
Popularizing these findings earlier this month were two HIV-positive journalists. Writing on the front page of the Nov. 8 Wall Street Journal, editor David Sanford described how new anti-HIV treatments had rescued him from death's door ("Last Year, This Editor Wrote His Own Obituary"). Two days later, Andrew Sullivan published his 8,400-word literary tour de force, "When AIDS Ends," in the New York Times Magazine. According to Sullivan, the success of new anti-HIV drugs has triggered the "twilight of an epidemic"--for those who can afford the $10,000-plus-a-year regimens. A diagnosis of HIV infection, he contends, "no longer signifies death," but "merely signifies illness."
Study after study has shown that in many patients, the triple-combo therapy so dramatically reduces the amount of HIV found in blood--their viral loads--that the most sensitive tests available cannot detect the virus. An "undetectable" viral load is not the same as being free of HIV, but many researchers believe that less virus equals less damage to the immune system. For certain, the new treatments are having a visible effect on the health of the HIV-infected, as David Sanford's Lazarus-like turnaround attests. Some AIDS researchers, encouraged by the early results with triple-combo therapy, are investigating whether it's possible to completely clear--"or eradicate"--HIV from the bodies of people who begin treatment shortly after becoming infected.
Given their personal struggles against AIDS, Sanford and Sullivan's exhilaration at this news is understandable. But their celebrations are premature--the defeat of AIDS is completely overstated. HIV still poses a sobering list of scientific unknowns, which the optimists dismiss far too quickly. With all best wishes to Sanford, it's foolhardy for him to say, "I've survived this scourge," and that because of the advent of protease inhibitors, "I am probably more likely to be hit by a truck than to die of AIDS." Sullivan's more daring pronouncement that "this ordeal as a whole may be over" is likely to mislead sick people in need of hope. And the argument that AIDS is conquered may also lend a sharper ax to the legislators who perennially argue to cut the AIDS-research budget.
There are plenty of reasons to be skeptical about the power of these new treatments. There are scant data to explain how long these new treatments will prevent disease and extend life--no formal studies have been completed that compare hundreds of treated people with hundreds of untreated people. Another downside to the drugs is that they often make people feel nauseated and can have serious toxicities. In some people, these drugs only work for a short time; in others, the drugs make HIV undetectable, but their immune systems are too damaged to rebound. HIV remains a stealthy foe: It can take refuge in body tissues (as opposed to blood), where the drugs have a harder time reaching. And the virus routinely mutates into strains that are resistant to every drug that has proven effective against it.
Sullivan's article notes these depressing findings alongside his good news. But there is plenty of bad news that he doesn't report. The lymph nodes (and other sites in the body) can be packed with HIV even when the virus is undetectable in the blood. At last summer's international AIDS conference, researchers described a patient who had been treated for 78 weeks with a combination of drugs, and in whom they could detect no virus. When he stopped taking his medicine, high levels of HIV returned in a week. An AIDS researcher told me last week of four patients who recently died from AIDS, even though their viral loads had become undetectable with the new drug treatments. Just because you drive a viral load to the point where it can't be detected doesn't mean the immune system returns to normal. There are also the practical obstacles to AIDS optimism. Taking two dozen or more pills a day, on a schedule, is a daunting task to carry out for years on end. Missed pills lower the potency of the treatment, opening the way to drug-resistant HIV mutants.
HIV has a long history of laughing last.
I'm not a defeatist, mind you. Measured optimism is warranted. Although the vast majority of HIV-infected people in the world cannot afford these new treatments, for those who can, the drugs will possibly stave off disease and death. But, because no one knows whether these new leases on life should be measured in weeks, months, years, or decades, balancing optimism and pessimism requires a delicate touch.
Consider the history of the drug AZT, which has seesawed in the public perception from panacea to poison and back again. When first approved by the FDA in 1987, AZT was hailed as a godsend. Then it was denounced as ineffective by activists, after larger studies showed that, when taken alone, the drug offered little except to the sickest people. Worse yet, many HIV-infected people viewed the drug as a worthless poison being hawked by researchers who were on the take from a greedy pharmaceutical company. Today, AZT is seen as a mediocre but useful medicine: It has a place in the triple-combo therapy, and it can prevent the transmission of HIV from infected mothers to their babies two-thirds of the time.
From here, many HIV researchers are putting their hopes on combining drug treatments with strategies that boost the immune system. For just one example, triple-combo therapy is now being tested in conjunction with interleukin-2, an immune-system messenger that theoretically can help rev up the natural machinery that clears the virus from the body.
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