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2 Refresher Course For J2J Fellows XVII International AIDS Conference Presenter: Bob Meyers, NPF & J2J

3 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.

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5 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

6 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 %.

7 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.

8 HIV/AIDS As A Medical/Scientific Issue

9 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.

10 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.

11 AIDS is caused by HIV, the Human Immunodeficiency Virus Courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases

12 In many ways HIV acts like most other viruses And the immune system treats it like any other virus

13 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

14 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,

15 Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases

16 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

17 Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases

18 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.

Days New virus assembly 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

20 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

21 Typical Course of HIV infection Graph courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases

22 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

23 CD4 Count in Phases of HIV Infection 5-14 days Incubation CD4 cell count 1-4 mo.4-10 years1-2 years Primary Presymptomatic AIDS Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota

24 The level of HIV in the blood predicts disease course Amount of Virus in Blood One year Rapid Progression Slow Progression Slide (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center

25 Immune system detects HIV and sounds the alarm

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27 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

28 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 Rantes Mip 1 alpha Mip 1 ß Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota

29 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

30 Function of the CD4 T Cell after infection 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 Rantes Mip 1 alpha Mip 1 ß Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota

31 (Pause) Why are we spending so much time on this science stuff?

32 So everyone will know how complex this is And so you will be able refute anyone who claims HIV does not cause AIDS

33 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

34 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

35 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,

36 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

37 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 

38 HIV replicates mainly in lymph tissue, the immune-system stronghold Images from The National Cancer Institute,

39 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

40 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

41 Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases

42 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.

43 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 destroyed—no discernible germinal centers Photos and information courtesy of Timothy Schacker, University of Minnesota

44 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.)

45 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

46 Antiretroviral drugs (ARVs) block HIV’s assault on 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 Rantes Mip 1alpha Mip 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

47 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 destroyed—no discernible germinal centers The same HIV-positive patient after 6 months on ARV treatment Germinal centers discernible again but lack healthy surrounding mantle Photos and information courtesy of Timothy Schacker, University of Minnesota

48 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.

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

50 So why is there no vaccine against, or a cure for, HIV/AIDS?

51 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

52 So until medicine and science can give us the answer … We have to look at ways to prevent HIV infections & AIDS

53 HIV/AIDS As A Public Health Issue

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 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 %.

56 A very informal way of looking at HIV transmission … You have to do something Or have something done to you To contract HIV

57 Vulnerable People Women –Especially in male-dominant cultures –In war zones –Sex workers Children –students Medical workers Men in risky relationships

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

59 Vulnerable Groups Local communities National defense Migrant workers Agriculture Education

60 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

61 Until we have a vaccine or a cure … We have to focus on prevention

62 Personal Prevention Condoms – Male or female Microbicides Limited sexual partners Clean needles male circumcision, for adults

63 Societal Prevention Developing of new drugs –Distribution of those drugs –Preventing mother-to-child transmission Development of Vaccines Sterile clinical environments Government & industry attitudes

64 Medicine & Public Health Compared for the Benefit of Journalists

65 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)

66 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

67 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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72 And if you’re going to view them as both, then you need two more basic definitions …

73 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 %.

74 Journalism Practice

75 In the next four days we’re going to look at a lot of issues, both as journalists and as concerned citizens...

76 …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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78 I believe that AIDS is curable… Despite all the failed vaccine trials Despite the failed scientific interventions Despite the difficulties at prevention…

79 HIV/AIDS is curable … through education

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81 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

82 Because we are educators, and given … The size of the epidemic The potential for its growth The impact on society The impact on people

83 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

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

85 And I think that is why we came here

86 Thank you!

87 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

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