The Virus Fights Back

At the World AIDS conference, hope mingles with troubling news about drug-resistant HIV

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

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