Method predicts likelihood of rapid AIDS development
The identification of a way to single out those HIV+ infants at highest
risk for the rapid and aggressive development of AIDS means that doctors
may now target these babies for early, powerful therapies, reported Emory
researchers in the Nov. 7 edition of The New England Journal of Medicine.
Infants who test positive for HIV can be put into two groups: those in whom
AIDS symptoms develop quickly and aggressively--within the first one to
two years of life--and those in whom symptoms may not appear for a number
of years. Until now, doctors have not known conclusively how to predict
which HIV+ infants will fall into which category.
Thymus dysfunction was common to the majority of HIV+ infants whose AIDS
symptoms progressed rapidly, reports Athena P. Kourtis, fellow; Andre J.
Nahmias, director, Division of Infectious Diseases, Epidemiology and Immunology
in the School of Medicine; and their colleagues, in their study of 232 infants
younger than six months. While the thymus organ located in the chest becomes
virtually nonfunctional in older age, it serves the important function in
children of producing T lymphocyte immune cells. In particular, it produces
the CD4+ helper T cells that are depleted by the AIDS virus. It also produces
CD8+ cytotoxic T cells. Both types of cells are involved in resistance to
HIV, as well as to other viruses and bacteria.
The researchers postulated that certain strains of AIDS not only deplete
mature CD4+ and CD8+ T cells in infants, but also inhibit production of
these cells by damaging the thymus. Thus, certain infants would exhibit
particularly low levels of these important cells--and would develop AIDS
An important part of the study was the team's comparison of infants with
acquired immune deficiency from HIV to infants with a type of congenital
immune deficiency known as the DiGeorge syndrome. Children with DiGeorge
syndrome have thymic defects and characteristically low CD4+ and CD8+ T
cell counts, as well as low CD5+ B cell counts. These B cells comprise the
majority of B lymphocytes.
The team did indeed find that the number of CD4+ T cells in the 17 HIV-infected
infants they characterized with a thymic-defect profile averaged 536 cells
per cubic milliliter compared with four to six times higher levels in 42
HIV-infected infants without the profile and in 168 control infants who
were exposed to, though not infected with, HIV. The team found a similar
distribution of CD8+ T cells among the three patient groups: 512 cells per
cubic milliliter among the HIV-infected infants with thymus defect profiles
compared to levels twice as high among the HIV-infected infants without
the profile and among HIV-exposed controls.
The researchers estimate this subgroup of HIV-infected infants with thymic-defects
represents about 15 percent of all HIV-infected children. They found that
82 percent of infants in this group would develop AIDS before their first
birthday and 38 percent would die; 96 percent would develop AIDS before
their second birthday and two-thirds would die. This compares with 34 percent
of infants in the no-thymic-defect group developing AIDS by age 2, and 3
"In this study, we have identified a subpopulation of HIV-infected
infants with an immunophenotype resembling that of patients with the DiGeorge
syndrome," the authors reported. "Our findings suggest that the
pathogenesis of disease in this group of infants may involve HIV-induced
dysfunction of the thymus...
"Thus, the bimodal pattern of progression in pediatric AIDS may largely
be explained by differences in the potential of (certain) HIV strains (with
particular affinity to the thymus and which can cross the placenta during
gestation) to cause early thymic disruption...," the authors report.
High-risk infants may be identified currently by blood test measurements
of the joint distribution of their CD4+ and CD8+ T cells counts, as well
as by obtaining CD5+ B cell counts, as early after birth as possible. Newer
tests being developed by the Emory group involving the virus may provide
even earlier methods of identification.
"The recent (CDC) recommendations for early preventive measures against
P. carinii pneumonia in all HIV-exposed children may prove particularly
beneficial in children under the age of six months," the authors reported.
"Therapeutic approaches will need to be more aggressive among these
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