Sloppy Treatment Impulses
Jamie is waving his arms above his head, in a gyrating rhythm that tracks the DJ's beats. I push through sweaty backs and prickly tricep stubble to reach him on the other side of the dance floor. I'm grinning as I approach Jaime, pleased to see him back in the mix. He rarely goes to the clubs. They don't offer him the joy they once did, since he can't dance and can't trick.
The excommunication from the dance floor was issued by his HIV meds, which triggered in him some embarrassing problems with diarrhea. As for tricking out, Jamie once told me that "wearing Depends makes for kind of a let down when the guy pulls your jeans off." Jamie is like that; while other guys might retreat behind bitter resignation, he jokes through the uncomfortable realities of fighting HIV.
So I'm beaming as I wordlessly approach him, and slip into the groove that's directing his motions. He's oblivious to me at first, caught up in the shimmering lights. When he finally spots me, his face explodes in a hearty laugh. "Hey, you!" he shouts, pulling me into a bear hug. We dance a few more sets, then buy champagne-priced bottles of water. I wink and tip my bottle in the direction of the dance floor. "I thought it was Stella who got her groove back," I tease.
"Oh, I'm okay," he says, flashing me the waistband of genuine CK briefs to prove his point.
"New regimen?" I ask.
"No, but I'm okay going out. The medicines only mess with my stomach on the days I'm taking them."
Suddenly the music recedes to a hollow echo, and I stare in panic at Jamie. "The days you take them . . . ?" I repeat numbly. "Tell me you're not taking a drug holiday. You've got to know that HIV mutates if you skip your meds."
"For a holiday, yeah, but this is something I plan. I stop all of them for the whole weekend. You know, like a structured treatment interruption."
I glance around at the happy bouncing faces on the dance floor, and realize that this is not the ideal environment for explaining the confusing logistics of Structured Treatment Interruptions, or their new nomenclature, Strategic Interrupted Treatment.
For the record, all of this began with the famous "Berlin patient." This anonymous guy became HIV infected in May of 1996, and started treatment almost immediately. He fell off of his meds twice. First, he developed a testicular infection that left him hospitalized for two weeks. He had forgotten his meds (don't ask me why he didn't ask at the hospital for more). Then after getting back on treatment, he caught hepatitis A, and couldn't hold anything down, so he stopped taking his meds again.
He returned to treatment one more time, but then came to feel that he was somehow better. He decided to stop taking his meds that November, and scientists have since discovered that his intuition was accurate -- he has shown no detectable HIV in his bloodstream for years. (No, he's not actually cured. Researchers can recover "competent" HIV from deep reservoirs in his tissues. But he is living without the burden of daily treatment or disease progression.)
The "miracle" of the Berlin patient hit the medical journals just as hopes for "eradication theory" were fading. That theory had held that patients who could keep their virus levels undetectable for just a few years would become "cured," because their body's defenses would finish mopping up what little HIV remained below our radar screens. In 1998, Dr. David Ho had to revise his original estimate of the countdown to a cure from 3.1 years to 18-20 years. Later that year, Dr. Robert Siliciano proved it would actually take 60 years of continuously successful therapy to finish pushing HIV out.
So if eradication is impossible, how had the Berlin patient inadvertently accomplished the next-best thing: treatment free health? Clinics all over the world exploded with theories, which they're testing out on a variety of patients. The general belief is that the Berlin patient, by sporadically exposing his body to high levels of HIV, retrained the sights of his immune system (cytotoxic T-lymphocytes) which would otherwise tend to "forget" how to spot HIV when the virus is kept undetectable. In essence, he had vaccinated himself.
In addition, while his immune system was re-targeting HIV, the virus was losing its memory of the medicines that it had once learned to evade. The virus became progressively more "sensitive" to attacks from the meds when it hadn't seen those meds in a while. In other words, it was overcoming drug resistance.
Or maybe not. Dr. Veronica Miller had reported in 1999 that the HIV in her patients had indeed become vulnerable to the meds again after a structured break. But at last year's conference, she reported that all of those benefits were short-lived, and that some patients were never able to bring their virus back under control again. Far from making HIV less of a threat, imposing a break on treatment may have opened the Pandora's box of drug resistance -- just like science used to warn drug holidays could do. Other researchers have concluded that increased Virologic Immunological Response (VIR) does result for ideal patients, but that it's a short-lived benefit.
Who are ideal patients for a possible SIT/STI? Unfortunately, my friend Jamie doesn't seem to be one of them. Most studies with long-term HIV-positive patients show that these treatment interruptions don't help. At the very best, they might provide a reprieve from side effects and leave the patient no worse off than he was before he took the break. At worst, the break may open the same Pandora's box that Miller's patients encountered.
The successes we've seen have almost always centered on treatment-naïve patients -- those who are either so newly infected that they were still enjoying the maximal impact of their new meds, or those who have been chronically infected, but never had any trouble at all keeping their virus way down low. Even then, only about one-third of these ideal patients enjoy even a temporary benefit from an SIT/STI.
Most of these studies are also way too small to provide any firm answers on how to stage a successful SIT/STI. Most enrolled only a half dozen or perhaps two dozen patients so far. The biggest study (a Swiss-Spanish group) is on its way to enrolling 122 patients, and thus far has found no benefit to SITs at all.
If any tentative conclusion seems to fall out, it may be this: Jamie's weekend escape is a recipe for disaster. Any benefits in terms of HIV "forgetting" the shape of its medicinal enemies, and the body "remembering" HIV's presence, seem to take at least a couple of weeks to accrue. The NIH's three-tiered study of a more cyclical Strategic Treatment Interruption found that the group that bounced off and on the meds too quickly (5 days on, 2 off) were on their way to treatment failure. That study arm closed, and the one week on/one week off doesn't seem to be faring much better -- one patient got worse, and the other six neither improved nor worsened. The only group that seems to have had some success is the one month on/one month off group, for whom viral load is rebounding less dramatically with each successive break.
I've spoken with friends for whom the SIT/STI approach has worked. With each round, they're able to stay off the meds longer, and their HIV peaks to lower levels than during their previous interruption. Yet a recent report in the Journal of Infectious Diseases warned that widespread use of STIs could significantly increase the prevalence of drug-resistant HIV throughout the positive population.
Confused yet? So am I, and I do this for a living! That's why I pulled Jamie aside to explain that SITs/STIs are not a "Do It Yourself" course offered at Homo Depot. Even if we do find the exact formula for timing and treatments, this will always have to be a physician-directed plan. If you planned to take one month off, for example, from your Zerit, Sustiva, and Crixivan, you'd better not stop all the meds at the same time. That's because they all clear out of the body at different rates. Your Crixivan would clear out fast, with the Zerit right behind it. That would leave Sustiva acting as a progressively weaker monotherapy, slowly trickling out of your body while HIV plots against it!
SITs/STIs are designed to work like judo; they pull the opposition out of sight just as HIV was trying to attack it. If you do decide to explore this subject, don't take a Sloppy Treatment Interruption like Jamie did. That's more like throwing half-punches at your opponent.
Our hope is that the mysteries of SITs/STIs will be washed away by science, so that every person living with HIV will be able to enjoy some breaks from the costs and side effects of their meds, and maybe even resensitize their virus to the treatments.
If you want to reap those benefits, be sure that you stage a structured treatment interruption.
Stephen Fallon is President of Skills4, Inc., a health-promotion and disease-prevention consulting firm based out of Ft. Lauderdale, offering professional trainings, grant writing services, and community-based workshops. Visit www.Skills4.org.
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