Intermittent drug treatment may actually be better than continuous treatment for some HIV-positive patients, researchers reported yesterday.
The research team, led by Franco Lori and Julianna Lisziewicz of Georgetown University, found that periodically stopping "triple therapy" apparently boosted the immune systems of two of three patients they studied, allowing the patients to safely forgo antiviral drugs for prolonged periods.
The findings, reported in The Lancet, a European medical journal, raise the possibility that HIV patients may be able to take lengthy breaks from their pill-heavy, occasionally unpleasant treatments, even if an outright cure remains beyond reach.
The strategy, however, runs counter to treatment recommendations for people infected with the human immunodeficiency virus (HIV). In general, they're advised to remain on triple therapy, without interruption, once they start.
Studies in recent years have shown that in most HIV patients, daily doses of three or more antiviral drugs will suppress virus growth to where it is no longer detectable in the bloodstream. In virtually all cases, however, the virus rebounds to measurable (and often quite high) levels within weeks of stopping treatment.
Lori and Lisziewicz believe that one reason HIV returns so quickly is that the body is unprepared to attack it after long periods of successful virus suppression. They theorize that exposing the immune system to HIV in a highly controlled way will stimulate the body's innate ability to fight back.
"It's a 'booster-shot' theory," said Lisziewicz, who with Lori is co-director of the Research Institute for Genetic and Human Therapy, which has facilities here and in Pavia, Italy.
The theory was based on the case of an unnamed German man who has become famous in the world of AIDS research simply as "the Berlin patient." He began triple therapy soon after infection, but stopped it two weeks later when he became ill with another infection. His virus returned, but disappeared when he resumed triple therapy a week later.
Four months into treatment, the Berlin patient got sick again and stopped his antiviral drugs. His virus did not return in the two weeks before he resumed them again. A month and a half later, he decided to stop them for good. To the astonishment of his physicians, his virus has remained undetectable in the bloodstream for more than three years. He isn't cured, however, for HIV can still be found, in viable form, in various cells and tissues.
The Georgetown team, and several other collaborators, enrolled three HIV patients and essentially reproduced the Berlin patient's interrupted course of treatment to see what would happen.
The three patients, one a middle-age gay man living in Washington, had never taken antiviral drugs. They had been recently infected, and their immune systems were not yet seriously damaged by the virus. They each took triple therapy for three weeks, stopped it for one week, and then resumed. Thereafter, at three-month intervals, therapy was stopped for one week, and not resumed until the HIV "load" in the blood rose to 5,000 viruses per milliliter of blood, which is well above the level of detection.
In the first patient, the viral load remained below 5,000 for six months after the second interruption of treatment. It eventually climbed above that threshold, and he resumed taking his pills. He is planning to interrupt therapy again in the next few weeks, Lori said.
The second patient's viral load rebounded quickly, as it does with most people, every time he stopped triple therapy. However, in the third patient--the Washingtonian--the amount of time the virus took to rebound got longer and longer after each interruption. After the last, he went 150 days before having to start taking his pills again.
"You can think of these intermissions as the same thing that happens with polio shots [vaccinations]," Lori said yesterday.
The Washingtonian in the study, who agreed to talk anonymously, said he was thrilled to be able to stop his medicines, even if he always had to restart them.
"I hated being on those drugs. I was on ones that were pretty easy to take, but I found they just made me feel wigged out. The swimmy-head feeling. So being off it was a real drug-holiday for me," he said.
Lori said that while he and his colleagues are excited by their findings, their strategy is still highly experimental and unproved. "In fact, we discourage patients and doctors, on their own, to imitate the Washington patient or the Berlin patient until further studies are done," he said.
In November, Lori and Lisziewicz began a study that will more rigorously test their theory. Forty HIV-infected people will be randomly assigned to get intermittent triple therapy or constant triple therapy. After six months, all of them will stop taking their drugs, and the researchers will see which (if any) patients' viruses remain low for a prolonged period.