Fauci Lab Presents New Data on AIDS Pathogenesis, Treatment at Retroviruses Conference

cellular activation by stimuli such as opportunistic infections and immunizations boosts HIV
replication.
"MSI-1436 and related compounds that interfere with cellular activation events warrant
further testing as possible therapies for the treatment of HIV-infected individuals," says Ms.
Kinter.
Audrey Kinter, et al. MSI-1436, a novel aminosterol, inhibits HIV replication in vitro and
in vivo infected mononuclear cells. Session 25, Abstract 231. Thursday, 4:00 p.m.
8. Loss of CD4+ T Cell Diversity in Late-Stage Disease Not Reversed by
Therapy
In a study of patients whose CD4+ T cell counts dropped from more than 500 cells/mm3
to under 50 cells/mm3, NIAID researchers found that certain types, or clones, of CD4+ T cells
may be permanently lost as disease progresses.
Therapies that increase CD4+ T cell numbers, such as interleukin-2 and protease
inhibitors, may boost the remaining clones, but appear to have little effect on the lost cell types.
The findings, says Dr. Fauci, "argue for early intervention before elements of the
immune system are irretrievably lost. In addition, prophylaxis for opportunistic infections may
remain important for patients who have rising T cell counts but may be missing part of their
T-cell repertoire."
Mark Connors et al. HIV induces changes in CD4+ T cell phenotype and repertoire that
are not immediately restored by antiviral or immune-based therapies. Session 39, Abstract
369. Friday, 11:00 a.m.
9. Cytokine Environment Influences HIV Phenotype
New in vitro data suggest that the presence or absence of certain cytokines influences
the relative rate of replication of different strains of HIV.
Early in the course of HIV disease, the main strains of HIV found in HIV-infected people
are macrophage-tropic (M-tropic) isolates. As disease progresses, T-cell line tropic (T-tropic)
strains of HIV appear, coincident with the decline of the immune system. People who have
mostly T-tropic strains of HIV replicating in their bodies are at considerable risk of disease
progression.
M-tropic and T-tropic isolates of HIV also are known as non-syncytia-inducing (NSI) and
syncytia-inducing (SI) strains, respectively, based on observed differences in their ability to
cause the formation of giant cells called syncytia in cell culture. Recent studies have shown
that NSI (M-tropic) strains, but not SI (T-tropic) strains are inhibited by immune system
molecules called beta-chemokines.
LIR researchers JoAn Monaco, Audrey Kinter and their colleagues have developed a
model system to determine whether the cytokine microenvironment of HIV-infected cell cultures
can be manipulated to influence the relative replication of NSI and SI strains of HIV.

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