Early Progression of Disease in HIV-Infected Infants with Thymus Dysfunction
Athena P. Kourtis, M.D., Ph.D., Christian Ibegbu, Ph.D., Andre J. Nahmias, M.D., M.P.H., Francis K. Lee, Ph.D., W. Scott Clark, Ph.D., Mary K. Sawyer, M.D., and Steven Nesheim, M.D.
Background Infants with congenital thymic deficiency (the DiGeorgesyndrome) have immunodeficiency and a characteristic patternof low CD4+ and CD8+ T-lymphocyte counts and low CD5+ B-lymphocytecounts. Because the thymus is essential for the generation ofCD4+ cells, we sought evidence of thymus dysfunction in infantsinfected perinatally with the human immunodeficiency virus (HIV).
Methods We studied the immunophenotypes of 59 infants with maternallytransmitted HIV, 5 infants with the DiGeorge syndrome, and 168infants exposed to HIV but not infected. The criteria for apresumed thymic defect were reductions in both the CD4+ andCD8+ T-cell subgroups during the first six months of life thatwere confirmed in a subgroup of infants by low counts of CD4+CD45RA+and CD4+CD45RO+ T cells and CD5+ B cells.
Results Of the 59 HIV-infected infants, 17 had immunophenotypessimilar to those of infants with the DiGeorge syndrome. Therisks of the acquired immunodeficiency syndrome (AIDS) by theages of 12 and 24 months were, respectively, 75 percent and92 percent in these 17 infants, as compared with 14 and 34 percentin the other 42 infants (P<0.001). Nine of the HIV-infectedinfants with the DiGeorge-like immunophenotype (53 percent)died within six months of the progression to AIDS, as comparedwith only three of the other infants (7 percent, P = 0.006).
Conclusions In some infants infected perinatally with HIV, apattern of lymphocyte depletion develops that resembles thepattern in congenital thymic deficiency. Since HIV disease progressesrapidly in such infants, they may be candidates for early antiviraltherapy and attempts at immune reconstitution.
Source Information
From the Division of Infectious Diseases, Epidemiology and Immunology, Department of Pediatrics, Emory University, 69 Butler St. SE, Atlanta, GA 30303, where reprint requests should be directed to Dr. Nahmias.
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