AIDS Research at the NIH: A Critical Review

cell regulation, homeobox developmental genetics, lymphocyte transcription factors, cytokine networks, HIV
infection and AIDS, Chlamydia trachomatis and the vasculitides (autoimmune vascular inflammatory
conditions). Their AIDS work includes basic, clinical and international components. They are studying the
NF-kappa-B (NK-kB) family of transcription factors active in lymphocyte activation and HIV replication, as
well as neuroimmunologic mechanisms of HIV. Work published in 1991 documented that HIV is never
totally latent in the body, and that even in earlier stages of infection active expression can be detected by
HIV mRNA PCR. Other work showed that the viral burden is 5-10 times higher in the lymphoid organs than
in the blood. This raised the likelihood that measuring viral load in the peripheral blood provides an
inaccurate picture of the overall viral load. LIR workers have also published important work on HIV-infected
monocytes, shown in vitro the possibility of infecting CD8+ T cells, and shed light on how cytokines (e.g.,
TNF-alpha, TGF-beta, IL-6) affect HIV expression and the immune response. The Laboratory of
Infectious Diseases (LID), chief Robert Chanock, studies dengue virus, rotaviruses, salmonella,
respiratory, influenza viruses, woodchuck virus, HAV, HBV, HCV, SIV and FeLV. The Laboratory of
Molecular Microbiology (LMM), chief Malcolm Martin, studies the molecular genetics and protein products
of mycoplasmas, oncoviruses, endogenous mammalian retroviruses (e.g., MuLV), HIV and SIV. They are
busy looking at the HIV vpu gene and protein product, HIV-encoded inhibitory sequences, env mutants,
vif structure and function, molecular determinants of target cell tropism, rev-RRE interactions, ultraviolet
(UV) light activation of HIV transcription, nef and oncogenic Ras protein comparisons, tat and TAR. The
Laboratory of Parasitlc Diseases (LPD), chief F.A. Neva, studies Entamoeba histolytica, Trypanosoma
cruzi Giardia lamblia, Schistosoma mansoni and Toxoplasma aondii. LPD work showed how schistosome
parasites utilize host TNF-alpha to reproduce faster, tuming host defense cytokines to their own use - a
strategy which resembles one used by HIV. The Laboratory of VIral Diseases (LVD), chief Bernard
Moss, studies pox, vaccinia, adeno-, parvo-, influenza, herpes and HIV. They are studying the two newest
members of the human herpesvirus family, HHV-6 and HHV-7. They are also working on vaccinia virus
vectors with HIV peptides as potential HIV vaccines. The Laboratory of Persistent Viral Diseases
(LPVD), chief Bruce Chesebro, works on rabies, Friend retrovirus, Aleutian disease virus, scrapie,
experimental allergic encephalomyelitis (EAE), equine infectious anemia virus (EIAV) and HIV cell tropism.
DIVISION OF AIDS (DAIDS) DAIDS runs most extramural AIDS programs for NIAID. It has three
programs. Dan Hoth, MD is the Director, DAIDS. The Deputy Director is Jack Killen, MD. Marilyn
Kunzweiler runs the DAIDS Administrative Office. Susan Ellenberg, PhD, heads the Biostatistics Research
Branch (BRB). Peggy Johnston, PhD, is Associate Director of the Basic Research + Development Program
(BRDP). Lewellys Barker, MD, MPH is Associate Director of the Clinical Research Program (CRP), and
Bill Duncan, PhD, heads the Treatment Research Operations Program (TROP).
DAIDS Office of the Dlrector (OD) Each level of the NIH recapitulates the one immediately above it
("Bureaucracy recapitulates hierarchy"). Thus, DAIDS, like NIAID or the NIH itself, has an "OD". The
Director of DAIDS, Dan Hoth, came over from the NCI Developmental Therapeutics Branch (DTB) in
October 1987. At NCI, Hoth had run several clinical research projects and had also worked on the Group
C Cancer Drug system which in certain respects paved the way for later developments such as Treatment
IND and Parallel Track. Hoth's Special Assistant, Deborah Katz, RN, MPH, is an invaluable source of
information pertaining to DAIDS activities. DAIDS administers 37% of the entire NIH AIDS budget. Its
responsibilities are enormous. Yet the DAIDS OD lacks strategic long-range planning staff.
Blostatistics Research Branch (BRB) The BRB provides statistical support for DAIDS clinical trials,
including the ACTG, the CPCRA, DATRI, and the AVEG. BRB staff were among the first to forge
constructive links with activists in 1989. BRB should work to streamline data collection and analysis in
NIAID clinical trials. This is the only way that more could be done with current, limited funds. Cutting back
on irrelevant data points can improve the efficiency of the ACTG and other systems. BRB can also help
FDA and industry to continue developing more useful trial designs. Whether nucleosides confer a survival
benefit is also unknown still unknown, and assessments of survival should be developed.

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