The significance of these findings is far reaching:
- A vaccine (as we now understand vaccines) for preventing HIV will probably
never be effective. Antibodies against HIV are characteristic of infected
individuals, and their disease does not progress because of a shortage
of antibodies. In fact, by most definitions persons infected with HIV are
immune to the virus; only their T cells are still susceptible.
- Drugs (such as AZT) that suppress virus replication will be curative
only if given very early in the infection process before the lymph nodes
are "seeded," and then only if given in large amounts or in combination.
Treating a person in the later stages of HIV infection may suppress the
disease, but only as long as the virus remains in the lymph nodes. The
disease will begin again as soon as the drugs are discontinued or interrupted.
The antiviral drugs now used will be effective only if maintained at high
levels and changed often to counter drug resistance by the virus.
- Curative treatment will depend on eliminating the virus reservoir and
on causing the virus attached to the germinal center cells to drop off,
or to be destroyed, by some as yet unknown cellular process.
- The disease process in humans is exactly mimicked by a similar virus, simian immunodeficiency virus (SIV), in monkeys. Now the conditions for treatment of people infected with HIV can be readily worked out using nonendangered laboratory-raised (rhesus) monkeys.
Figure 4 Diagram of the lyphatic system.
Fifteen years ago when I first began to work with this mysterious disease
called AIDS, the task seemed hopeless. I remember my thoughts, after months
of working in dirty and unkempt labs with strains of a virus that had killed
someone, when I awoke at three in the morning with a sore throat and fever.
Would I die? Had I infected my wife? Was that cut from a broken flask in
the lab filled with the deadly virus? Believe me, all this runs through
a person's mind until the results from the blood tests are back and you
test negative for the third time in six months.
In the past two years hope for those infected with HIV has changed drastically.
Many of us "old timers" now believe we have turned the corner.
Using the conventional HIV drugs in combinations will allow the indefinite
suppression of new virus formation and will allow HIV-infected people a
long disease-free period.
To cure the disease entirely requires finding ways to empty out the lymphoid
tissues. I believe this is possible using the monkey as a test subject.
While many people object to using animals to find a cure for a disease,
animals can be raised for just such a purpose. They must be treated properly
and humanely, and they can save hundreds of thousands of humans from a deadly
and debilitating sickness. Whether the recent experiment of transplanting
baboon cells into humans (or some other radical and imaginative approach)
will solve the AIDS problem will not be known for some time.
These are the challenges of HIV research and treatment. There is now hope
that sweeping new approaches are possible to attack this virus that uses
the human immune system against itself.
Further Reading
Fauci, A. S., et al. 1991. Lymphoid germinal centers are
reservoirs of HIV-1 RNA. Journal of Infectious Diseases 164: 10517.
Fox, C. H. 1992. Lymphoid germinal centers are reservoirs of HIV infection
and account for the apparent latency of infection. AIDS Research and
Human Retroviruses 8 (5): 756758.
Fox, C. H., et al. 1994. HIV in infected lymph nodes. Nature 370:
256.
Fox C. H., and M. Cottler-Fox. 1992. The pathobiology of HIV infection.
Immunology Today 13: 353356.
Heath, S.L., et al. 1995. Follicular dendritic cells and human immunodeficiency
virus infectivity. Nature 377: 740744.
Pantaleo, G., et al. 1993. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 362: 355358.
Editor's Note
Cecil H. Fox holds bachelor's and master's degrees in microbiology from
Trinity University, a PhD in biology from Clark University, a doctorate
in biochemistry from Lund University (Sweden), and a third advanced degree
in experimental pathology from the Karolinska Institute in Stockholm. For
20 years he was a Senior Scientist at the US National Institutes of Health.
In 1982, after a broad career in chemistry and pathology, he became fascinated
with HIV disease and concentrated on the pathobiology of primate (immunodeficiency)
lentiviruses. In 1992 he founded Molecular Histology Inc., a private corporation
devoted to pathobiology.
Cecil H. Fox is available for one day in-service training programs on AIDS
and HIV disease in school systems and in interactive student programs. He
can be reached by telephone at 301-216-1564.
