ACTG 315 Preliminary Results: Drug Cocktail Restores Partial Immune Function

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suggest that physicians should be cautious about backing off from 01 prophylaxis once it is
indicated, despite early increases in CD4 counts."
In the three-month analysis, Dr. Lederman's group found that the increase in CD4+ T
cells could be attributed to both more memory cells (those that have encountered HIV before)
and more naive cells (those not exposed to HIV or another antigen before), while naive cells
are primarily responsible for the rise in CD8+ T cells. Meanwhile, the percentage of activated
CD4 and CD8 T cells fell, arid average plasma levels of TNF-CL (tumor necrosis factor alpha, a
protein that is usually very high in people with HIV) dropped, as the median plasma HIV RNA
burden fell by more than 700-fold.
The investigators also analyzed the repertoire of T-cells according to a variable region
on its receptor, VP, which can exist in 24 different varieties in humans. Patients with dramatic
but restricted patterns of VP expansion experience more rapid progression of HIV disease than
other patients. In ACTG 315, VP repertoires were highly perturbed at baseline and remained so
at 12 weeks. Functional immune response, as measureid by delayed-type hypersensitivity (a
skin test used to assess cellular immune function) and lymphocyte proliferation assays (to
assess immune memory), was only partially restored.
The team is still evaluating the virologic effects of HAART on lymphoid tissue. Follow-up
studies also will examine immunologic function after longer term HAART, and after changes in
therapy for participants who fail to respond. Data are being analyzed to ascertain the
mechanism underlying restoration of circulating T cells in patients receiving HAAR T
"ACTG 315 is the first of a series of studies developed by the new ACTG
Immunology/Immune-Based Therapies Research Agenda Committeej" comments Dr. Fox, "that
takes full advantage of the capabilities of the Immunology Advanced Technology Laboratories.
This resource will greatly expand our understanding of HIV immunopathogenesis, opening up

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