NPF: AIDS 2010 Refresher for Vienna Journalists

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Refresher CourseFor

J2J FellowsXVIII International AIDS Conference

Vienna, Austria Presenter: Bob Meyers, NPF & J2J

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Why are we doing this?To make sure that all J2J

participants in Cape Town are on a level playing field, with all other J2Jers and all other journalists.

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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

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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/AIDSAs A

Medical/Scientific Issue

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What Does AIDS Do In the Body?

• AIDS is a disease of the immune system

• The immune system is a network of cells and organs throughout the body

• HIV destroys the immune system.

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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.

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AIDS is caused by HIV, the Human Immunodeficiency

Virus

Courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases

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In many waysHIV acts like most other

virusesAnd the immune system treats it

like any other virus

Video from Howard Hughes Medical Institute

• http://www.hhmi.org/biointeractive/disease/hiv_life_cycle.html

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http://www.hhmi.org/biointeractive/disease/hiv_life_cycle.html

http://www.hhmi.org/biointeractive/disease/hiv_life_cycle.html

Scroll through the following PPTs on your own, or

Jump to # 53

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But in a few crucial waysHIV 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

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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.

Images from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm

16Slide 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 body’s own cells that have been infected– Excreting molecules such as “chemokines” that

interfere with viral replication

18Slide 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 called “CD4”. HIV attaches to this molecule and, like a lock and key, uses it to enter the cell.

• “Helper” means that this cell “helps” other parts of the immune system do their job. If the immune system is an orchestra, this cell is the conductor.

• “T” is short for “Thymus-derived” and is a type of immune cell. There are other T-cells, such as killer T-cells.

202-3 Days

New virusassembly

HIV replicates in CD4 cells. Amount of 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 train heading toward a crash

• Viral load indicates the speed of the train

• CD4 count indicates the distance to the crash

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CD4 Count in Phases of HIV Infection

5-14 days

Incubation

CD

4 ce

ll c

ount

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 bloodpredicts disease course

Am

ou

nt

of

Vir

us

in B

loo

d

One year

Rapid Progression

Slow Progression


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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 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

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Function of the CD4 T Cell

Resting CD4 Cell

Activated CD4 Cell

Macrophage, Dendritic Cell,or other Antigen Presenting Cell

Promote B-cell Antibody Response (also called “Humoral” response)

Promote Killer T-cells (also called “CTL”short for “Cytotoxic T-Lymphocyte”)

Secrete ß Chemokines

RantesMip 1 alphaMip 1 ß


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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

• By activating CD4 cells to mobilize a counterattack, the immune system is actually “feeding” HIV

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Function of the CD4 T Cellafter infection

Resting CD4 Cell

Activated CD4 Cell





RantesMip 1 alphaMip 1 ß


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(Pause)

Why are we spending so much time on this

science stuff?

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So everyone will know how complex this is

And so you will be able refute anyone who denies

that HIV causes AIDS

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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.

Graphic (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center

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New virusassembly

Antibodies try to snare HIV

B cell


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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.

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 scientific reason that HIV is so

difficult to stop once it is in the body

… and why AIDS is so difficult to cure.

Look

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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 lymphoid “germinal 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 the immune system’s stronghold.

• But: The fight between HIV and the immune system is balanced at a standoff for many years

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Slide 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 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.

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Lymph tissue in HIV-negative and HIV-positive people

HIV-negativeperson

Upper left-hand corner: roundgerminal center surrounded by healthy mantle

HIV-positivefor 5 years, noARV treatmentAll “geographical” features destroyed—nodiscernible 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.)

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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 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

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Antiretroviral drugs (ARVs) block HIV’s assault on the CD4 T-cell

Resting CD4 Cell

Activated CD4 Cell





RantesMip 1alphaMip 1 ß

Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota. ARV graphic (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center

ARVs

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Lymph nodes in HIV-negative, HIV-positive, and ARV-treated

patients

HIV-negativeperson

Upper left-hand corner: Round “germinal center” surrounded by healthy mantle

HIV-positivefor 5 years, noARV treatmentAll “geographical” features destroyed—nodiscernible germinal centers

The same HIV-positivepatient after 6 monthson ARV treatmentGerminal centers discernibleagain 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 Peumonia

• Thrush (candidiasis)

• Cyrptococcal meningitis

• Can be prevented short-term with INH. Cured with combination antibiotics.

• Can be prevented with Cotrimoxazole (Bactrim) and cured with that and other antibiotics.

• Can be cured with fluconazole.

• Can be cured and prevented from recurring with fluconzazole.

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(This ends Mark’s brilliant review of HIV/AIDS)

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So why is there no vaccine against,

or a cure for, HIV/AIDS?

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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 and science 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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A very informal way of looking at HIV transmission

…

• You have to do something

• Or have something done to you

• To contract HIV

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Vulnerable People

• Women– Especially in male-dominant cultures– In war zones– Sex workers

• Children– students

• Medical workers

• Men in risky relationships

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Transmission

• Unprotected sexual contact

• IV drug use

• Unsafe clinical environment

• Mother-to-child transmission

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Vulnerable Groups

• Local communities

• National defense

• Migrant workers

• Agriculture

• Education

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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

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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

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Medicine Public Health

• Primary focus on individual

• Diagnosis & treatment • Medical care• Social sciences as an

elective part of PH education

• Laboratory & bedside

• Primary focus on population• Emphasis on prevention• Interventions aimed at

environment, behavior, lifestyle, medical care

• Social science as an integral part of PH education

• Laboratory & field work

• (after H. Fineberg, 1990)

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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 Physical

Inactivity• Alcohol Consumption• Microbial Agents• Toxic Agents• Motor Vehicle Crashes• Incidents involving Firearms• Sexual Behaviors• Illicit Use of Drugs

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Each of the following pictures can be viewed …

• as a story of an individual

• Or as the story of community issue

• Or both

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And if you’re going to view them as both, then you need two more basic

definitions …

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Journalism Practice

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In the next four days we’re going to

look at a lot of issues, both as

journalists and as concerned citizens...

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…But right now I want to briefly

discuss this question – do we as journalists have a

special obligation to cover HIV/AIDS?

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I believe that AIDS is curable…

• 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

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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

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And the fact that print, or broadcast & online

journalists cover everything from ….

• Poor people• Rich people• National defense

• Marginalized populations

• Sex workers• Our country’s future

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Then I think we can educate many

segments of the population about what

we know.

And I think that is why we came here …

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Thank you!

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Acknowledgements

• Mark Schoofs, The Wall Street Journal• 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• Howard Hughes Medical Institute

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Documents

NPF: AIDS 2010 Refresher for Vienna Journalists