[Letter to ACT UP Treatment and Data Committee from National Institutes of Health]

DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
National Institutes of Health
w 43U National Institute of Allergy
and Infectious Diseases
Bethesda, Maryland 20892
Building:. 31
Room: 7A03
Phone: [phone]
Fax: [phone]
April 30, 1993
Treatment and Data Committee
ACT UP
135 W. 29th Street, #10
New York, NY 10001
Dear Members of the Treatment and Data Committee:
I am responding to your letter of April 22 in which you listed a number
of questions concerning stage dependent treatment of HIV infection. I have
enclosed a copy of your letter to me, and I will answer it by question number
to reflect the actual questions in your letter.
1. It is unclear at the present time what is the precise role of HIV
in lymph node deterioration. Since the lymph node is made up of multiple
components, including B cells, T cells, follicular dendritic cells (FDCs),
monocyte/macrophages, and bone marrow derived dendritic cells, among others,
the process of deterioration of the lymph node is probably multi-factorial.
HIV certainly infects CD4+ T cells and probably monocyte/macrophages in the
lymph nodes. Although there has been a single paper demonstrating the
infection of FDCs, we and others have been unable to readily demonstrate the
actual infection of these FDCs. Therefore, the current thinking is that
although FDCs may get infected, the FDCs deteriorate by mechanisms which are
related generally to HIV but not necessarily to the direct involvement of the
virus as an infection of FDCs themselves. It is possible that the environment
of the lymph node, either by the infiltration of cells such as CD8+ cells or
perhaps by a disruption of the balance between T cells and B cells in the
lymph node, contributes to the FDC deterioration. In addition to FDC
deterioration, there is depletion of the immune competent cells in the lymph
node. This may be more related to direct infection of HIV or of the response
(either cytolytic or cytokine-related) of immune competent cells to HIV
infected cells. It is important to keep a totally open mind as to what the
mechanisms are of the deterioration of the lymph node. This is one of the
main reasons why we are continuing to actively study lymph nodes in
individuals at various phases of disease. We have just begun to understand
the process of progression of immune dysfunction within the lymphoid tissue
from early through late disease.
2. You are correct to say that the initial trapping of virions in
FDCs is an extracellular process. AZT cannot affect a virion that is already
formed. However, the virions do arise from HIV infected cells themselves.
During the spread of infection from one CD4+ T cell to another, reverse

transcriptase is utilized and so AZT, in its limited effectiveness, can block
111111 55710950239IIIIIIIIIII II III111liII
5571095.0239.009