AIDSWEEKLY Plus; Monday, July 13 & 20, 1998
Daniel J. DeNoon, Senior Editor
The thymus is an important immune organ in children, who need the organ to generate CD4(+) T cells.
Early attempts to provide thymus transplants to HIV(+) children with thymic dysfunction and rapidly progressive HIV disease were only partially successful. But now that more potent antiretroviral therapy is available, the technique may greatly improve survival in selected pediatric patients.
"Now that we are doing much better with treatment, the issue of which patients might benefit from thymus transplants or from any other methods to improve their effective host resistance mechanisms is much more complex," said Andre J. Nahmias of Emory University, Atlanta, Georgia. "Although we believe our research is a significant step forward, we still need to determine which patients would actually benefit from transplants and in which ones antiretrovirals might be sufficient."
Nahmias reported data on thymus transplants in four children in a poster presentation to the XII World AIDS Conference, held June 28- July 3, 1998, in Geneva, Switzerland.
The technique permitting the transplants was developed by Richard Hong of the University of Vermont. Nahmias, Hong, and colleagues performed thymic transplants in four critically ill children. Only one - an 11-year-old who contracted HIV infection from a blood transfusion given during heart surgery - survived more than four years.
The child remains well with no AIDS symptoms.
Nahmias and co-workers previously showed that some children born with HIV infection have a thymic defect strikingly similar to that seen in HIV negative children born without a functional thymus (DiGeorge syndrome). Nearly all such children have rapidly progressive HIV disease (Kourtis et al., NEJM, 1996;335:1431-6; Nahmias et al., 4th Conf Retro and Opportun Infect, 1997, Abstract 532; Kourtis et al., Int Conf AIDS, 1996, Abstracts Tu.B.2315 and Tu.B.2313).
Adult patients with early HIV disease have memory T cells capable of initiating immune responses to pathogens to which they have previously been exposed. Children, however, lack such immunologic memory and depend much more on thymic function.
"We have proven that the methodology of thymic transplants is simple, requiring only one day of hospitalization and little use of potentially harmful drugs to prevent rejection of the graft as is necessary in bone-marrow transplantation," Nahmias said. "No graft- versus-host rejection has occurred and the main problem has been poor virus control and sometimes poor compliance."
The Emory researcher said that ongoing studies are underway to find a way to identify HIV strains that attack the thymus. He suggested that thymic transplant may be applicable to some adults with HIV disease.
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