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Lecture Summaries
Thursday, December 6, 2007
LECTURE ONE
From Outbreak to Epidemic
Bisola O. Ojikutu, M.D., M.P.H.
Webcast 10:00 a.m.-11:00 a.m. ET & PT
In 1981, an obscure and deadly disease surfaced. Previously
healthy homosexual men in the United States
began arriving at clinics with rare cancers and infections
usually seen in people with weakened immune systems.
Most of them died. The medical community was baffled and the public anxious. As the cases multiplied, so did
the questions. Who is at risk? What is causing the disease? Why does it lead to failure of the immune
system? And most important: Can it be stopped from spreading? The new disease was named acquired
immune deficiency syndrome, or AIDS, and it has now killed more than 25 million people worldwide. After the
initial outbreak, different sectors of the public health, medical, scientific, and advocacy communities mobilized
in response to the deadly epidemic. They focused on surveillance—that is, detecting and mapping the
disease—and prevention.
Break
11:00 a.m.–11:30 a.m. ET & PT
Lecture Two
AIDS and the HIV Life Cycle
Bruce D. Walker, M.D.
Webcast 11:30 a.m.-12:30 p.m. ET & PT
The first AIDS cases—otherwise healthy young men
with multiple infections and cancers—were a mystery
to even the most seasoned physicians. The symptoms
pointed to a major defect in the immune system.
Further investigation found swollen lymph nodes,
another sign of immune stress. A clear hypothesis
emerged: the cells of the immune system were directly
infected. Tissue cultured from patients’ lymph nodes
revealed a new virus—a retrovirus. This type of virus
contains RNA that it converts to DNA once it infects
human cells. Named human immunodeficiency virus, or
HIV, its viral code integrates into the host genome, a
safe haven from most drugs, and causes lifelong infection.
HIV infects lymphocytes throughout the body,
disabling the very cells that defend against invading
viruses. With a weakened immune system, patients are
vulnerable to infections that are normally easy to fend
off. A detailed understanding of the HIV life cycle, from
cell attachment and entry to translation and assembly of
new viruses, can help researchers identify targets for
drug therapy.
Friday, December 7, 2007
Lecture Three
Drugs and HIV Evolution
Bisola O. Ojikutu, M.D., M.P.H.
Webcast 10:00 a.m.-11:00 a.m. ET & PT
In 1987, four years after HIV was identified, the Food
and Drug Administration (FDA) approved the use of
azidothymidine (AZT) to slow the progression of HIV
infection to full-blown AIDS. AZT targets reverse transcriptase,
an enzyme essential to HIV replication in
lymphocytes. Unfortunately, HIV evolves rapidly and
develops resistance to AZT, making single-drug therapy
with reverse transcriptase inhibitors ineffective. In 1996,
a new class of antiretroviral drugs, called protease
inhibitors, was approved. This development led to a
treatment strategy called highly active antiretroviral
therapy (HAART), a drug “cocktail” combining multiple
drugs that target at least two steps in the HIV life cycle.
As a result, deaths from AIDS in developed nations have
dropped significantly, making HIV a chronic, treatable
disease, not a death sentence. Since 1987, more than 20
drugs have been approved for use in combination to
treat HIV infection, and more are in the pipeline. New
drug classes include chemical agents that inhibit the
virus’s entry into the cell, integration into the host
genome, and maturation.
Break
11:00 a.m.–11:30 a.m. ET & PT
Lecture 4
Vaccines and HIV Evolution
Bruce D. Walker, M.D.
Webcast 11:30 a.m.-12:30 p.m. ET & PT
The global HIV epidemic continues to spread: 40 million
people are infected worldwide. While drugs are essential
in the battle against HIV, a vaccine would be a major
advance. A vaccine, for example, can be preventive and
does not require frequent dosing. HIV’s ability to evolve
rapidly is a major hurdle in developing a vaccine. HIV
replication uses a reverse transcriptase enzyme that
converts viral RNA into DNA. The enzyme is poor at
reading and correcting mistakes. With successive replication
cycles, alterations in viral genes accumulate,
resulting in the evolution of new viral traits. HIV shows
more variability in a single person than the total viral
variability seen across a global influenza epidemic. This
rapid HIV evolution makes it difficult to pick a stable
protein sequence to target for vaccine development.
Currently, the focus is on keeping HIV in check rather
than developing a completely preventive vaccine.
Individuals whose native immunity has kept HIV under
control for more than 25 years may provide clues for
creating a vaccine.
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