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Elite suppressor on chemo? No problem
Surprising finding: 'Nothing happened.'
Elite suppressors are that 1% or fewer of HIV patients who do not develop signs of disease progression despite living for years without treatment. But what could make their status change from elite controller to an HIV patient with progressing HIV disease?
Scientists are learning through case studies some possible answers.
For example, one recent study involved a patient who had suppressed HIV for more than a decade when he was discovered to have elevated protein and some neurologic symptoms.
"A work-up was done, and doctors found that he had Waldenstrom's Macroglobulinemia, a tumor of B cells of the immune system," says Adam Spivak, MD, a clinical fellow at the Johns Hopkins University School of Medicine of Baltimore, MD.
"In these patients, B cells start growing and aren't dying," Spivak adds. "It can be a fatal tumor, so he underwent several different modes of chemotherapy to treat it."
One of the patient's providers on the oncology team notified Joel N. Blankson, MD, PhD, an associate professor at the Johns Hopkins University School of Medicine, about the case.
"Joel was alerted that there was a patient with HIV who despite not being on therapy had a good T cell count and no virus around, and he was about to undergo chemotherapy," Spivak says. "So we had an opportunity to study a patient who had no problem controlling his HIV infection on his own and was about to undergo major chemotherapy with the intention of suppressing his immune system."
Blankson, Spivak, and co-investigators were especially interested in learning how this patient would fare while on rituximab, which contains an antibody that attacks human B cells.
"It turns out to be a very good treatment for diseases where B cells are getting people into trouble because when you administer it, the treatment takes B cells out of circulation," Spivak explains.
But what would this mean to an HIV patient whose immune system has suppressed HIV?
"What's not well understood is what antibodies do against the virus," Spivak says. "We have evidence from other papers that antibodies don't help to control the virus very well because the virus can mutate and change a lot faster than the antibodies can, so they lose the race."
On the other hand, everyone who has HIV infection has an antibody to HIV. For most people the antibodies provide no protection and patients need to take antiretroviral therapy to survive. But no one knows whether this also is true in the case of elite suppressors.
"With elite suppressors, it's possible perhaps that they have a better antibody response and that's what is helping them control their virus," Spivak says. "If that was the case, then you can imagine this patient who now has a tumor and is given rituximab to wipe out his B cells might lose control of the virus."
Oncologists needed to give him this treatment to save his life, but they recognized that by doing so, the patient could develop a worsening HIV disease.
"His viral load could go up and his T cells could go down if the antibodies are making the difference," Spivak says.
"So we followed the patient and measured the amount of virus in his body before, during, and after chemotherapy," he says. "The surprising thing that happened was that nothing happened."
The elite suppressor continued to fully control HIV even though he had few antibodies in his system.1
"The rituximab did its job and wiped out his tumor, as well as temporarily wiping out the antibody-producing part of his immune system," he explains. "We could imagine that to have a successful antibody response you'd need to constantly make new antibodies, but this drug wipes out the ability to make new antibodies."
But even after five months and 10 cycles of rituximab treatment, the patient's viral load remained undetectable even as his CD4 T cell count declined, he adds.
"With any patient receiving rituximab you would expect their white blood cell count to go down, and we saw that happen, but we didn't attribute it to HIV," Spivak says.
The case study's chief limitation is that it was an observation of what happened to one patient, but its findings still are important to advancing scientists' understanding of what is going on with elite suppressors.
"This is the first time that anyone has described a patient who was an elite suppressor receiving rituximab," Spivak says. "It gives us a window into seeing whether antibodies are responsible for controlling the virus."