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Refresher Course
For
J2J Fellows
XVII International AIDS Conference
2
Why are we doing this?
To make sure that all J2J
participants in Mexico City are on
a level playing field, with all other
J2Jers and all other journalists.
3
4
We will look at HIV/AIDS
in three ways. As a …
• Medical/Scientific Issue
• Public Health Issue
• Medicine & Public Health compared for
the benefit of journalists
5
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 %.
6
Big footnotes
1. The following segment was written by Mark
Schoofs, one of the founders of J2J, in 2002,
and presented at the XIV International AIDS
Conference in Barcelona, July 4, 2002 (Mark
is now a reporter at The Wall Street
Journal)
2. Bob Meyers did some editing prior to the XVII
AIDS Conference in Mexico City, in 2008.
7
HIV/AIDS
As A
Medical/Scientific
Issue
8
What Does AIDS Do
In the Body?
9
What Does AIDS Do
In 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.
10
AIDS is caused by HIV,
the Human Immunodeficiency
Virus
12
But in a few crucial ways
HIV differs from other viruses
When the immune system responds after
HIV attacks it, HIV turns the immune system
counter-attack to its own advantage
This allows HIV to persist in the body for
years and finally destroy the immune system
13
The immune system is a
network of organs and cells
• Mucosal barriers:
Vagina, rectum,
mouth.
• Lymphatic vessels:
the immune
system’s
bloodstream
• Lymph nodes &
GALT: cleansing
centers
• Thymus, spleen,
bone marrow etc. 14
Images from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm
15
Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
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 body’s own cells that have been infected
– Excreting molecules such as “chemokines” that interfere
with viral replication
16
Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
17
The CD4+ T-helper Cell
New virus
assembly
2-3 Days
19
Slide (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
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
20
Typical Course of HIV infection
21
Graph courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
Relationship Between CD4 and
Plasma HIV viral load
• AIDS is like a train
heading toward a
crash
• Viral load indicates
the speed of the train
22
CD4 Count
in Phases of HIV Infection
Incubation
Primary
Presymptomatic
CD4 cell count
AIDS
Rapid Progression
Slow Progression
One year 24
Slide (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
Immune system detects HIV
and sounds the alarm
25
26
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 fragments
called “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 itself
into an army of identical cells
• These “activated” cells stimulate other immune-system
cells, such as B-cells, which make antibodies, and killer
T-cells, which kill infected cells
27
Function of the CD4 T Cell
Secrete ß Chemokines
Rantes
Mip 1 alpha
28
Mip 1 ß
Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota
HIV prefers to infect
activated CD4 T-cells
• 93-99% of HIV infects activated CD4
cells, which are HIV’s favorite “food”
– HIV occasionally infects unactivated or
“resting” CD4 cells, where for years it can
hide from the immune system
Secrete ß Chemokines
Rantes
Mip 1 alpha
30
Mip 1 ß
Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota
(Pause)
32
How antibodies work
• Antibodies work by
binding to particular
fragments of HIV as
the virus floats in the
blood or lymph.
• These fragments are
called “epitopes.”
• When the antibody
binds to the epitope, it
“neutralizes” the virus,
rendering it harmless.
33
Graphic (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
Antibodies try to snare HIV
New virus
assembly
B cell
34
Slide (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital,
Harvard Medical School, Partners AIDS Research Center
But HIV eludes antibodies
• HIV is sheathed in an
“envelope”
– The envelope is the most
mutable part of HIV, so HIV
keeps changing its coat,
making it impossible for
antibodies to bind.
• HIV uses part of the
envelope to enter cells
– But these critical parts are
cloaked with carbohydrates
molecules. Antibodies
rarely bind effectively to
carbohydrates.
35
Image from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm
Killer T-cells
are “big guns” in viral infections
36
This is one scientific
reason that HIV is so
difficult to stop once it is
in the body
… and why AIDS is so difficult to
cure.
Look
37
HIV replicates mainly in lymph
tissue, the immune-system
stronghold
38
Images from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm
Site of HIV Production and
Storage
40
41
Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
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 immune
system, combined with HIV’s 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.
42
Lymph tissue in HIV-negative
and HIV-positive people
HIV-negative HIV-positive
person for 5 years, no
ARV treatment
Upper left-hand corner: round All “geographical”
germinal center surrounded features destroyed—no
by healthy mantle discernible germinal centers
43
Photos and information courtesy of Timothy Schacker, University of Minnesota
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.)
44
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 don’t rise to
pre-HIV levels.
– But usually enough immune recovery to fight off most
infections.
• Therefore, ARVs take the place of drugs to
prevent or treat most OIs
• But antiretroviral drugs are expensive
45
Antiretroviral drugs (ARVs) block
HIV’s assault on the CD4 T-cell
Macrophage, Dendritic Cell,
or other Antigen Presenting Cell
Promote B-cell Antibody
Response (also called
“Humoral” response)
Activated CD4
Cell
Promote Killer T-cells
(also called “CTL”
Resting CD4 short for “Cytotoxic
Cell T-Lymphocyte”)
ARVs
Secrete ß Chemokines
Rantes
Mip 1alpha
46
Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota. ARV graphic (slightly adapted) courtesy
Mip 1 ß
of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
Lymph nodes in HIV-negative,
HIV-positive, and ARV-treated
patients
48
(This ends Mark’s brilliant review
of HIV/AIDS)
49
So why is there no
vaccine against,
or a cure for,
HIV/AIDS?
50
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
51
So until medicine and
science can give us the
answer …
We have to look at ways to
prevent HIV infections & AIDS
52
HIV/AIDS
As A
53
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 %.
54
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 %.
55
A very informal way of
looking at HIV transmission
…
56
Vulnerable People
• Women
– Especially in male-dominant cultures
– In war zones
– Sex workers
• Children
– students
• Medical workers
• Men in risky relationships
57
Transmission
• Unprotected sexual contact
• IV drug use
• Unsafe clinical environment
• Mother-to-child transmission
58
Vulnerable Groups
• Local communities
• National defense
• Migrant workers
• Agriculture
• Education
59
If there is infection, these are
possible movements of HIV
• IDU or Sex worker
or Unknowingly
infected person
• Spouse or Partner
– Child (in utero)
• Blood contact
• Hospital environment
• Unknown
60
Until we have a vaccine
or a cure …
We have to focus on prevention
61
Personal Prevention
• Condoms – Male or female
• Microbicides
• Limited sexual partners
• Clean needles
• male circumcision, for adults
62
Societal Prevention
• Developing of new drugs
– Distribution of those drugs
– Preventing mother-to-child transmission
• Development of Vaccines
• Sterile clinical environments
• Government & industry attitudes
63
Medicine & Public Health
64
Medicine Public Health
65
Leading Causes of Death
In the United States
In the Year 1900 In the Year 2000
• Influenza
•
• Tobacco
Pneumonia
•
• Poor Diet and Physical
Tuberculosis
Inactivity
• Gastritis • Alcohol Consumption
• Heart Disease • Microbial Agents
• Cerebrovascular Diseases • Toxic Agents
• Chronic Nephritis • Motor Vehicle Crashes
• Accidents • Incidents involving Firearms
• Cancer and other Malignant • Sexual Behaviors
Tumors
• Illicit Use of Drugs
• Early Infancy Diseases
• Diphtheria
66
Each of the following
pictures can be viewed …
• as a story of an individual
• Or as the story of community issue
• Or both
67
68
69
70
71
And if you’re going to
view them as both, then
you need two more basic
definitions …
72
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 %.
73
Journalism Practice
74
In the next four
days we’re going to
look at a lot of
issues, both as
journalists and as
concerned citizens...
75
…But right now I
want to briefly
discuss this
question – do we as
journalists have a
special obligation to
cover HIV/AIDS?
76
77
I believe that AIDS is
curable…
• Despite all the failed vaccine trials
• Despite the failed scientific interventions
• Despite the difficulties at prevention…
78
HIV/AIDS is curable …
through education
79
80
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
81
Because we are educators,
and given …
82
And the fact that print, or
broadcast & online
journalists cover everything
from ….
• Poor people • Marginalized
• Rich people populations
• National defense • Sex workers
• Our country’s future
83
Then I think we can
educate many
segments of the
population about what
we know.
84
And I think that is why
we came here
85
Thank you!
86
Acknowledgements for
Mark Schoofs’ presentation
• Anthony S. Fauci & Greg Folkers, National
Institute of Allergy and Infectious Diseases
• Bruce D. Walker & Marylyn Addo,
Massachusetts General Hospital, Harvard
Medical School, Partners AIDS Research
Center
• Timothy Schacker, University of Minnesota
• Laurie Garrett, Newsday, & Omololu Falobi,
Journalists Against AIDS Nigeria
• Bob Meyers & Nena Uche, National Press
Foundation
• The Wall Street Journal & The Village Voice 87
88