Perspectives on interleukin-7 therapy in HIV infection.
OBJECTIVE
HIV infection is characterized by depletion of CD4 T cells and altered immune function, leading to severe immune deficiency. Mechanisms leading to this T-cell depletion are not completely understood. Potent antiretroviral therapy restores T-cell counts and improves prognosis. Apart from antiviral therapy for the infection, immunotherapies such as interleukin-7 that influence T-cell homeostatic mechanisms are undergoing clinical evaluation. Because of its pleiotropic effects on developing and mature T cells, interleukin-7 may help to restore immune function during HIV infection.


RESULTS
Recent studies explored the therapeutic use of interleukin-7 in simian immunodeficiency virus models and in HIV-infected patients. Interleukin-7 can help to restore CD4 T-cell number and function.


CONCLUSIONS
Numerous recent findings highlight the importance of interleukin-7 pathway impairment in the pathogenesis of HIV infection. Notably, interleukin-7 levels increased with advancing CD4 T-cell lymphopenia, whereas interleukin-7 receptor expression is downregulated mainly on CD8 T cells. Therapeutic trials conducted in monkeys and in humans (phase I) have provided evidence on the role of interleukin-7 in thymopoiesis and in restoration of T-cell functions. Interleukin-7 appeared to be well tolerated and to have no deleterious effects on viral load. These results should be confirmed in larger phase I/II studies.
Service d'Immunologie Clinique, Hopital Henri Mondor, Université Paris, Creteil, France.
Jean Daniel
JD
Lelièvre
Yves
Y
Lévy