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Refresher Course
For
J2J Fellows
Presenter: Bob Meyers, NPF & J2J
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Why are we doing this?
To make sure that all journalists
are on a level playing field in their
knowledge of HIV/AIDS
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We will look at
HIV/AIDS in threeways. As a
Medical/Scientific Issue
Public Health Issue
Medicine & Public Health compared forthe benefit of journalists
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Some basic definitions
HIV Human Immunodeficiency Virus
AIDS Acquired Immune Deficiency Syndrome
Medicine a focus on the individual
Public health a focus on populations
Incidence the number of new cases arising in a given population
in a given time
Prevalence the proportion of people with HIV at a specific point
in time; expressed as a %.
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HIV/AIDS
As A
Medical/Scientific
Issue
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What Does AIDS DoIn the Body?
AIDS is a disease of the immune
system The immune system is a networkof
cells and organs throughout the body
HIV destroys the immune system.
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What Does AIDS DoIn the Body?
HIV primarily attacks one type of cell that is
crucial to the immune system: The CD4 T-
helper cell After exposure, the body cannot fight off
infections, and so it succumbs to opportunistic
infections such as TB, pneumonia, etc., which
is why AIDS is a syndrome.
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AIDS is caused by HIV,
the Human ImmunodeficiencyVirus
Courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
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In many ways,
HIV acts like most other
virusesAnd the immune system treats it
like any other virus
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Video from Howard Hughes Medic
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But in a few crucial ways
HIV differs from other viruses
When the immune system responds after
HIV attacks it, HIV turns the immune systemcounter-attack to its own advantage
This allows HIV to persist in the body for
years and finally destroy the immune system
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The immune system is a
networkof organs and cells
Mucosal barriers:Vagina, rectum,mouth.
Lymphatic vessels:the immunesystemsbloodstream
Lymph nodes &GALT: cleansingcenters
Thymus, spleen,
bone marrow etc.Images from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm
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15Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
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The immune system is complex
and interactive Immune-system cells detect invading viruses and
bacteria
Immune system cells mobilize each other by: Direct cell-to-cell contact
Excreting messenger molecules such as cytokines
Immune system cells destroy invading viruses by: Excreting antibodies that snare free-floating virus
Killing the bodys own cells that have been infected
Excreting molecules such as chemokines that interferewith viral replication
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17Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
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The CD4+ T-helper Cell
CD4+ means that the cell displays(expresses) a molecule on its surface calledCD4. HIV attaches to this molecule and, like alock and key, uses it to enter the cell.
Helper means that this cell helps other partsof the immune system do their job. If the immunesystem is an orchestra, this cell is the conductor.
T is short for Thymus-derived and is a type ofimmune cell. There are other T-cells, such askiller T-cells.
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2-3 Days
New virus
assembly
HIV replicates in CD4 cells. Amount o
virus produced determines disease course
Slide (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
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New research suggests that
This time frame may be a matter of
HOURS, not days
Which could be one factor in failure of recent
vaccine trials
Inserted by Bob Meyers, 2008
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Typical Course of HIV infection
Graph courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
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Relationship Between CD4 and
Plasma HIV viral load
AIDS is like a trainheading toward acrash
Viral load indicatesthe speed of the train
CD4 count indicatesthe distance to thecrash
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CD4 Count
in Phases of HIV Infection
5-14 days
Incubation
CD4
cellco
unt
1-4 mo. 4-10 years 1-2 years
PrimaryPresymptomatic
AIDS
Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota
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The level of HIV in the blood
predicts disease course
Amoun
tof
VirusinB
lood
One year
Rapid Progression
Slow Progression
Slide (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
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Immune system detects HIV
and sounds the alarm
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At the cellular level
Macrophages and dendritic cells eat HIV Macrophage comes from macro for big and phage for eat.
So macrophages are Big Eaters, or scavenger cells
These scavenger cells cut up the virus into fragmentscalled antigens or epitopes
They present these viral fragments to other cells,including CD4+ T-cells Each CD4+ T-cell can recognize only one epitope
When it meets its particular epitope, the CD4 T-cell clones itselfinto an army of identical cells
These activated cells stimulate other immune-systemcells, such as B-cells, which make antibodies, and killerT-cells, which kill infected cells
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HIV prefers to infect
activatedCD4 T-cells
93-99% of HIV infects activated CD4
cells, which are HIVs favorite food
HIV occasionally infects unactivated or
resting CD4 cells, where for years it can
hide from the immune system
By activating CD4 cells to mobilize a
counterattack, the immune system is
actually feeding HIV
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Function of the CD4 T Cell
after infection
Resting CD4Cell
Activated CD4Cell
Macrophage, Dendritic Cell,or other Antigen Presenting Cell
Promote B-cell Antibody
Response (also calledHumoral response)
Promote Killer T-cells(also called CTL
short for CytotoxicT-Lymphocyte)
Secrete Chemokines
RantesMip 1 alpha
Mip 1 Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota
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(Pause)
Why are we spending
so much time on thisscience stuff?
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How antibodies work
Antibodies work bybinding to particularfragments of HIV as
the virus floats in theblood or lymph.
These fragments arecalled epitopes.
When the antibodybinds to the epitope, itneutralizes the virus,rendering it harmless.
Graphic (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
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New virus
assembly
Antibodies try to snare HIV
B cell
Slide (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital,
Harvard Medical School, Partners AIDS Research Center
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But HIV eludes antibodies
HIV is sheathed in anenvelope The envelope is the most
mutable part of HIV, so HIVkeeps changing its coat,
making it impossible forantibodies to bind.
HIV uses part of theenvelope to enter cells But these critical parts are
cloaked with carbohydratemolecules. Antibodiesrarely bind effectively tocarbohydrates.
Image from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm
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Killer T-cells
are big guns in viral infections
Antibodies snare free-floating virus
But viruses infiltrate cells
They turn the cells into factories that churn out
thousands of copies of themselves
Inside the cells, they are protected from antibodies
HIV also mutates to escape the antibodies
Killer T-cells kill cells that HIV has infected
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This is one scientificreason that HIV is so
difficult to stop once it isin the body
and why AIDS is so difficult to
cure.Look
HIV replicates mainly in lymph
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HIV replicates mainly in lymph
tissue, the immune-system
stronghold
Images from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm
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Site of HIV Production and
Storage
Photos and slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota
Lymph tissue with HIV stained
to look bright. Stars are cells
producing HIV.
Close up of several cells in
lymph tissue producing HIV
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HIV in the lymph nodes
The lymph nodes normally trap viruses in the lymphoidgerminal centers and cleanse the viruses from the body.
The lymph nodes trap HIV, but doing so activates CD4 T-cells. Therefore, lymph nodes provide food for HIV:
activated CD4+ T-cells. HIV prefers to be in the very place where the immune
system kills most other viruses. HIV sets up camp in theimmune systems stronghold.
But: The fight between HIV and the immune system is
balanced at a standoff for many years
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40Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
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HIV destroys the lymph nodes
HIV causes persistent lymph-node swelling, or
lymphadenopathy, one of the signs of HIV
infection.
Chronic, long-lasting activation of the immunesystem, combined with HIVs disruption of the
normal immune regulation, causes physical
destruction of the lymph nodes.
The lymph nodes can no longer trap and destroy
HIV. The delicate balance tips in favor of HIV.
L h i i HIV i
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Lymph tissue in HIV-negative
and HIV-positive people
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HIV-negative
personUpper left-hand corner: round
germinal center surrounded
by healthy mantle
HIV-positive
for 5 years, noARV treatment
All geographical
features destroyedno
discernible germinal centers
Photos and information courtesy of Timothy Schacker, University of Minnesota
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The consequences of HIV
infection As HIV slowly wins the battle, the immune system
can no longer repel some infections.
These are called opportunistic infections (OIs for short)
because they take the opportunity given to them by the
weakened immune system.
These other infections are what kills people. HIV
itself does not (though it can cause dementia.)
A ti t i l d (ARV )
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Antiretroviral drugs (ARVs)
attack HIV itself They stop HIV from replicating, but they do not
eradicate HIV from the body
They allow the immune system to recover Not full immune reconstitution. Lymphoid tissue often
retains signs of damage; CD4 cells often dont rise topre-HIV levels.
But usually enough immune recovery to fight off mostinfections.
Therefore, ARVs take the place of drugs toprevent or treat most OIs
But antiretroviral drugs are expensive
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Lymph nodes in HIV-negative
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Lymph nodes in HIV-negative,
HIV-positive, and ARV-treated
patients
HIV-negative
person
Upper left-hand corner:
Round germinal center
surrounded by healthy mantle
HIV-positive
for 5 years, noARV treatment
All geographical
features destroyedno
discernible germinal centers
The same HIV-positive
patient after 6 monthson ARV treatment
Germinal centers discernible
again but lack healthy
surrounding mantle
Photos and information courtesy of Timothy Schacker, University of Minnesota
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Without ARVs, many non-HIV OIs can
be cured or prevented cheaply
Tuberculosis
Pneumocystis Carinii
Pneumonia
Thrush (candidiasis)
Cyrptococcalmeningitis
Can be prevented short-termwith INH. Cured withcombination antibiotics.
Can be prevented withCotrimoxazole (Bactrim) and
cured with that and otherantibiotics.
Can be cured with fluconazole.
Can be cured and preventedfrom recurring withfluconazole.
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So why is there novaccine against,
or a cure for,HIV/AIDS?
U f t t l th
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Unfortunately, these are some
of the responses
The virus is incredibly complex and operates in a
way rarely seen before
Theories about how HIV operates have all had
failings Drug development takes time, and is expensive.
When testing a new drug, the risk to the
individual trial patient must be weighed against
the hoped-for benefit
Global HIV Vaccine Enterprise
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So until medicine andscience can give us the
answer We have to look at ways to
prevent HIV infections & AIDS
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HIV/AIDS
As A
Public Health Issue
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Some basic definitions
HIV Human Immunodeficiency Virus
AIDS Acquired Immune Deficiency Syndrome
Medicine a focus on the individual
Public health a focus on populations
Incidence the number of new cases arising in a given populationin a given time
Prevalence the proportion of people with HIV at a specific point
in time; expressed as a %.
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Some basic definitions
HIV Human Immunodeficiency Virus
AIDS Acquired Immune Deficiency Syndrome
Medicine a focus on the individual
Public health a focus on populations
Incidence the number of new cases arising in a given populationin a given time
Prevalence the proportion of people with HIV at a specific point
in time; expressed as a %.
A very informal way of
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A very informal way oflooking at HIV transmission
You have to do something
Or have something done to you To contract HIV
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Vulnerable Groups
Local communities
National defense
Migrant workers
Agriculture
Education
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Until we have a vaccine
or a cure We have to focus on prevention
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Personal Prevention
Condoms Male or female
Microbicides
Limited sexual partners
Clean needles
male circumcision, for adults
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Societal Prevention
Developing of new drugs
Distribution of those drugs
Preventing mother-to-child transmission
Development of Vaccines
Sterile clinical environments
Government & industry attitudes
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Medicine & Public Health
Compared for the
Benefit of Journalists
Medicine Public Health
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Medicine Public Health
Primary focus onindividual
Diagnosis & treatment
Medical care
Social sciences as anelective part of PHeducation
Laboratory & bedside
Primary focus on population Emphasis on prevention Interventions aimed at
environment, behavior,lifestyle, medical care
Social science as an integralpart of PH education
Laboratory & field work
(after H. Fineberg, 1990)
L di C f D th
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Leading Causes of Death
In the United States
In the Year 1900
Influenza
Pneumonia
Tuberculosis
Gastritis Heart Disease
Cerebrovascular Diseases
Chronic Nephritis
Accidents
Cancer and other Malignant
Tumors
Early Infancy Diseases
Diphtheria
In the Year 2000
Tobacco
Poor Diet and PhysicalInactivity
Alcohol Consumption Microbial Agents
Toxic Agents Motor Vehicle Crashes
Incidents involving Firearms Sexual Behaviors Illicit Use of Drugs
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And if youre going toview them as both, then
you need two more basicdefinitions
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Journalism Practice
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I believe that AIDS is
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I believe that AIDS iscurable
Despite all the failed vaccine trials
Despite the failed scientific interventions
Despite the difficulties at prevention
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HIV/AIDS is curable
through education
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Journalists are educators
We research difficult situations
We show people what we have learned
We give them information
so they can improve their lives
so they can improve society
Because we are educators,
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Because we are educators,and given
The size of the epidemic
The potential for its growth
The impact on society
The impact on people
And the fact that print, or
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p ,broadcast & online
journalists cover everythingfrom .
Poor people
Rich people National defense
Marginalized
populations Sex workers
Our countrys future
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Then I think we caneducate manysegments of the
population about whatwe know.
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Thank you!
Acknowledgements
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Acknowledgements
Mark Schoofs, The Wall Street Journal Anthony S. Fauci & Greg Folkers, NationalInstitute of Allergy and Infectious Diseases
Bruce D. Walker & Marylyn Addo,
Massachusetts General Hospital, HarvardMedical School, Partners AIDS ResearchCenter
Timothy Schacker, University of Minnesota
Laurie Garrett, Newsday, & Omololu Falobi,Journalists Against AIDS Nigeria
Howard Hughes Medical Institute
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