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Refresher Course
For J2J Fellows Presenter: Bob Meyers, NPF & J2J

Why are we doing this?

To make sure that all journalists are on a level playing field in their knowledge of HIV/AIDS

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 %.

HIV/AIDS As 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.

What Does AIDS Do In the Body?

HIV primarily attacks one type of cell that is crucial to the immune system: The CD4 Thelper 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.

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 ways, HIV acts like most other viruses

And the immune system treats it like any other virus

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Video from Howard Hughes Medica

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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 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 systems 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

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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 bodys own cells that have been infected Excreting molecules such as chemokines that interfere with viral replication

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Slide 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.
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HIV replicates in CD4 cells. Amount of virus produced determines disease course

New virus assembly

2-3 Days

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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
Inserted by Bob Meyers, 2008

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Typical Course of HIV infection

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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 CD4 count indicates the distance to the crash
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CD4 Count in Phases of HIV Infection

Incubation Primary Presymptomatic

CD4 cell count

AIDS

5-14 days

1-4 mo.

4-10 years

1-2 years

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Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota

The level of HIV in the blood predicts disease course

Amount of Virus in Blood

Rapid Progression

Slow Progression One year

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 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

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 short for Cytotoxic T-Lymphocyte) Secrete Chemokines Rantes Mip 1 alpha Mip 1
Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota

Resting CD4 Cell

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HIV prefers to infect activated CD4 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

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 short for Cytotoxic T-Lymphocyte) Secrete Chemokines Rantes Mip 1 alpha Mip 1
Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota

Resting CD4 Cell

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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.
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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

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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 carbohydrate molecules. Antibodies rarely bind effectively to carbohydrates.
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Image from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm

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

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

Site of HIV Production and Storage

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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Photos and slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota

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 Tcells. 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 systems 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

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 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.
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Lymph tissue in HIV-negative and HIV-positive people

HIV-negative person
Upper left-hand corner: round germinal center surrounded by healthy mantle

HIV-positive for 5 years, no ARV treatment

All geographical features destroyedno discernible germinal centers
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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.)

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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 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 HIVs 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 short for Cytotoxic T-Lymphocyte) Secrete Chemokines Rantes Mip 1alpha Mip 1
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Resting CD4 Cell

ARVs

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

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, no ARV treatment

All geographical features destroyedno discernible germinal centers

The same HIV-positive patient after 6 months on ARV treatment

Germinal centers discernible again but lack healthy surrounding mantle
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Photos and information courtesy of Timothy Schacker, University of Minnesota

Without ARVs, many non-HIV OIs can be cured or prevented cheaply

Tuberculosis Pneumocystis Carinii Pneumonia 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 fluconazole.

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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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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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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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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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Transmission
Unprotected sexual contact IV drug use Unsafe clinical environment Mother-to-child transmission

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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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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
Primary focus on individual Diagnosis & treatment Medical care Social sciences as an elective part of PH education Laboratory & bedside

Public Health
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 youre going to view them as both, then you need two more basic definitions

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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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Journalism Practice

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Lets 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 countrys future

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Then I think we can educate many segments of the population about what we know.

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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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