HIV Drug Boosts Immune System Sharply

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HIV Drug Boosts Immune System Sharply  By , MedPage Today Staff WriterReviewed by Zalman S. Agus, MD; Emeritus Professor at the University ofPennsylvania School of Medicine.September 23, 2005ROCHESTER, Minn., Sept. 23-A short course of the protease inhibitor Viracept(nelfinavir) boosts the immune system dramatically, opening an avenue tobetter cancer vaccines, researchers at the Mayo Clinic here have found.The discovery that the protease inhibitor spurs the output of newlymphocytes from the thymus may have many potential applications, saidimmunologist McKean, Ph.D.In addition to better cancer vaccines, it may also prove valuable in othersituations where the immune system is compromised, especially in olderpatients, he and colleagues suggested in the online edition of the journalAIDS.Using a relatively new method of tracking the output of the thymus -- dubbedT-cell receptor excision circles or TRECs -- they were able to show thatViracept, and presumably other protease inhibitors, stimulates the thymus toproduce more T-cell precursors. The output increased by a factor of between10 and 1,000.The largest organ at birth, the thymus shrinks over a lifetime, which is onereason the immune system weakens with age. "It has been known for a numberof years that HIV patients [who begin taking antiretroviral drugs] have anincrease in their thymic output," Dr. McKean said, but it was unclear why.HIV attacks the thymus, which produce cells that are precursors toperipheral T-cells, so lowering the amount of virus in a patient might helpthe thymus, he said. Or the drugs might be acting directly on the organ,causing it to produce more new-born immune cells.In fact, it's the latter, Dr. McKean and colleagues found.The researchers studied thymic output in seven HIV-negative health-careworkers, ages 24 to 61, who had been accidentally exposed to the virus.All were given 28 days of prophylactic treatment with antiretroviral drugs,including Viracept, and five of the seven showed sharply increased output ofnew lymphocytes. None went on to develop HIV.Because the patients were healthy, the improvement could not be a result ofrelieving HIV pressure on the thymus, Dr. McKean said."Even older patients had a significant increase in thymic output," Dr.McKean said, raising the possibility that a short course of proteaseinhibitors might be useful in elderly patients with a compromised immunesystem or chronic disease.He cited a report this week in The Lancet that suggest current flu vaccinesare not as effective as previously thought in people over 65. "That's anobvious target for this," he said.Dr. McKean also said he and colleagues are hoping to begin a study withinsix months, in which autologous cancer vaccines will be tested inconjunction with protease-inhibitor boosting of the thymus."We're going to see if we can boost thymic output, put new T-cells out inthe periphery, and have those cells respond to the cancer vaccine," he said.HIV drugs are known to cause a range of side effects, including such thingsas kidney stones and body fat redistribution, but Dr. McKean said a shortcourse of a protease inhibitor wouldn't have such consequences.Primary source: AIDSSource reference:Graham DB et al. Increased thymic output in HIV-negative patients afterantiretroviral therapy. AIDS 2005; 19(14):1467-1472. Rey A. Candelaria Munster, IN