Punctuated’ HIV meds planned for TB patients
Can set-point for AIDS be kept low?
Researchers at Case Western Reserve University in Cleveland were the first to find convincing evidence that TB accelerates the progress of HIV (and, it turned out, vice versa). Now researchers at the school’s TB Research Unit want to see whether a two-pronged approach to treating TB in HIV-positive patients can work to effectively delay the onset of AIDS.
In a trial at the research unit’s field site in Uganda, TB patients co-infected with HIV would get a standard course of TB therapy, accompanied by a short course of antiretroviral therapy (ART). Researchers reason that the short burst of ART — dubbed "punctuated therapy" — would staunch the flow of certain cytokines triggered by the body’s immune response to TB. And, because those cytokines trigger viral replication, stopping their flow might dramatically delay progress of the virus.
"What we’re trying to do is develop a new notion of how to manage HIV," says Chris Whalen, MD, associate professor of epidemiology and biostatistics at Case Western. "We’re trying to test the hypothesis that punctuated immune therapy during periods of intense immune activation may delay the time of immune suppression for months or even years."
The hypothesis dovetails with another theory HIV clinicians have been testing, at least in places where the HIV-infected have ready access to ART. Instead of starting ART immediately upon diagnosis, current thinking has it that perhaps it’s better to delay until CD4 counts drop to 500 or perhaps even as low as 350, explains Whalen.
The ability to delay ART would obviate plenty of difficulties associated with noncompliance (patients who don’t feel symptomatic, after all, are more likely to skip doses) and with some of the adverse effects turning up with long-term use of antiretrovirals.
A way to keep replication slow?
More important, Whalen says, it may be that there are two stages associated with management of HIV, each associated with its own "set point." If punctuated immune therapy could be used to halt the cascade of cytokines that accelerate viral replication, it could be that the set-point could be held at the first stage, and HIV therapy could thus be delayed for a time. "Instead of dipping down to 200, maybe we could keep a patient’s CD4 count at 350 or 400, or wherever they started," he says.
In Africa, targeting TB makes sense. "It tends to occur earlier in the course of HIV, when immune set-points would presumably still be relatively high," Whalen notes. In the United States, other events that trigger intense immune activation might be found — bacterial pneumonia, perhaps. Again, the idea would be to treat such patients briefly with antiretrovirals and determine whether the progress of their HIV could be arrested for a time.
The intervention carries with it certain risks, such as viral rebound and the development of drug resistance, Whalen concedes. "We may find it’s detrimental to withdraw [ART]," he says. If not, punctuated therapy would prove especially beneficial on a continent where most people will never be able to afford a lengthy course of HIV drugs.
If all goes according to plan, the trial will begin this fall. Then, if results are as Whalen hopes, the country may roll the pilot out on a broader scale within two to three years.
"Uganda is poised to be a leader" in Africa when it comes to providing HIV therapy for its people, Whalen says. "They’re very close to getting ART and training personnel to deliver it."
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