Uncovering the role of the thymus in AIDS progression

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(From left) Michael Saag, MD, University of Alabama at Birmingham, Mathias Lichterfeld, MD, PhD, Massachusetts General Hospital, and Jack T. Stapleton, MD, University of Iowa.

HIV-infected patients who maintain undetectable levels of the virus are known as elite controllers – they have high or “normal” CD4 cell counts and behave just like HIV-negative people, said Mathias Lichterfeld of Harvard Medical School at a press conference Friday during the 49th Annual Meeting of the Infectious Diseases Society of America.

Fending off HIV likely requires a lot of their immunological resources, according to the study abstract he presented at the meeting. “This suggests that specific regenerative immunological mechanisms are operational in these patients.”

That points scientists towards the thymus, which is where lymphocytes – a type of white blood cell – are produced and mature.

“Elite controllers who have non-progressive disease have a very functional thymus, whereas it’s defective in others,” he said. That small portion of elite controllers goes on to develop AIDS, even without detectible HIV replication.

“We now know there is going to be destruction of CD4 cells even when there is no detectible virus,” said Michael Saag, MD, of the University of Alabama at Birmingham.  “From a treatment perspective – elite controllers have traditionally been put off to the side because they seemed to control the infection,” and now we know that’s not necessarily the case.

Somewhere from one to five percent of people living with HIV belong to this elite controller group, and an even smaller subset have progressive disease, Lichterfeld said.

What is the role of the thymus in this disease?

“We don’t have the answer,” Lechterfeld said,  “Just the observation that it’s important those who do not have huge amounts of HIV replicating – they are behaving very similarly to those who are replicating. Something is going on that we don’t understand at this point.”

Future research could concentrate on how this is possible, how people can have deficiencies in CD4 regeneration if HIV is not even detectible, and to what extent these patients can benefit from traditional HIV treatment.

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