HIV and AIDS. Disease caused by an infectious agent: Acquired Immunodeficiency Syndrome. a retrovirus

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1 HIV and AIDS Acquired Immunodeficiency Syndrome Disease caused by an infectious agent: a retrovirus 1

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4 گزارش موارد ثبت شده HIV/AIDS تا پایان تابستان سال 1392 اسالمی ایران در جمهوری %89.3 مجموعا نفر افراد مبتال به HIV/AIDS مردا %10.7 را زنا تشكيل ميدهند. در كشور شناسايي شده اند كهه آنها را در مقايسه اين آمار با موارديكه ابتال آنا در سال 1391 گزارش شده است اعتیاد تزریقی 52 درصد برقراری روابط جنسی 2/33 درصد و انتقال از مادر مبتال به وهکد 4/3 را تشهكيل داده است. در 11.4 درصد از موارد شناسايي شده در اين سال راه انتقهال نامشه ب بهوده و هيچ مورد جديد ابتال از راه خو و فرآوردههای خوني گزارش نشده است. 4

5 Human Immunodeficiency Virus 5

6 Retroviridae 6

7 Classification Lentivirinae: Visna in sheep HIV (Human Immunodefeciency Virus) 7

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11 Virus Receptors CD4 molecule, which is expressed on macrophages and T lymphocytes A second coreceptor is necessary for HIV-1 for entry to cells Chemokine receptors serve as HIV-1 second receptors The chemokine receptors are found on lymphocytes, macrophages, and thymocytes as well as on neurons and cells in the colon and cervix Integrin α4β7 appears to function as a receptor for HIV in the gut 11

12 HIV and AIDS Some people do not get AIDS Long term survivors Exposed uninfected persons The chemokine receptor story 12

13 HIV integration: pro 13

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15 HIV - The Virus Retrovirus Group-Specific Antigens p17: inner surface - myristoylated p24: Capsid p9: nucleocapsid associated with RNA GAG gene Polyprotein 15

16 HIV - The Virus Enzymes Retrovirus Polymerase (reverse transcriptase RNA dependent DNA polymerase) Integrase Protease (cuts polyproteins) POL gene Polyprotein 16

17 HIV - The Virus Retrovirus Two glycoproteins: gp160 gp120 and gp41 gp41 is fusogen that spans the membrane sugars ENV gene vaccine problem 17

18 Quasi species Heterogeneous populations of viral genomes are found in an infected individual. Reflects high rates of viral replication and the high error rate of the viral revers transcriptase. The regions of greatest divergence among different isolates are localized to the env gene 18

19 HIV - Life History Fusion at ambient ph No need for entry into lysosomes Syncytia Profound significance for AIDS progression: Spread from cell to cell Profound significance for therapy: Humoral antibody will not stop spread need cell-mediated response 19

20 HIV - The Virus 20

21 HIV & AIDS 21

22 Transmission Sexually (presence of STD increases likelihood of transmission). Blood or blood products Mother to child: In utero Perinatal (variable, dependent on viral load and mother s CD 4 count Post natal (breast feeding) 22

23 Transmission

24 Day 0 Path of the Virus HIV exposure at mucosal surface (sex) Day 0-2 Day 4-11 Virus collected by dendritic cells, carried to lymph node HIV replicates in CD4 cells, released into blood Natural History of HIV and Staging of HIV Day Virus spreads to other organs

25 Stages of HIV Infection Viral transmission (2-3 wks) Acute retroviral syndrome (2-3 wks) Seroconversion (2-4 wks) Asymptomatic chronic HIV infection (Avg. 8yrs) Symptomatic HIV infection/aids (Avg. 1.3 yrs) Natural History of HIV and Staging of HIV 25

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28 Immune response An immune response to HIV occurs 1 week to 3 months after infection plasma viremia drops and levels of CD4 cells rebound the immune response is unable to clear the infection completely, and HIV-infected cells persist in the lymph nodes 28

29 Clinical latency may last for as long as10 years. It is estimated that 10 billion HIV particles are produced and destroyed each day. It is estimated that every nucleotide of the HIV genome probably mutates on a daily basis. 29

30 HIV and AIDS 3. A latent state Latency of virus and of symptoms Virus persists in extra-vascular tissues Lymph node dendritic cells Resting CD4+ memory cells (last a very long time - a very stable population of cells) carry provirus 30

31 Dynamics of CD4 T cells in an Cell death apoptosis etc HIV infection Chronicallyinfected memory T cells with provirus Uninfected activated T cell Infection Long lived! Return to resting state Reactivation Uninfected unactivated memory T cell pool Cell death immune destruction Adapted from Saag and Kilby Nat Med 5: 609, 1999 Long lived! 31

32 Long term latent HIV Immune response T4 resting memory cell T4 activated It may be impossible to cure the patient of HIV Even if combination therapy stops HIV replication HIV production 32

33 CD4+ Memory cells provide a long-term, stable latent reservoir for the virus. Less than 1 cell per million resting CD4 T cells harbors latent HIV-1 provirus. It is unlikely that an HIV infection can be cured with standard therapy 33

34 Opportunistic infections Once CD4 count drops below 500, HIV infected person at risk for. The following diseases are predictive of the progression to AIDS: persistent herpes-zoster infection (shingles) oral candidiasis (thrush) oral hairy leukoplakia Kaposi s sarcoma (KS)

35 Oral Candidiasis (thrush)

36 Oral Hairy Leukoplakia Being that HIV reduces immunologic activity, the intraoral environment is a prime target for chronic secondary infections and inflammatory processes, including OHL, which is due to the Epstein-Barr virus under immunosuppressed conditions

37 Kaposi s sarcoma (KS) Kaposi s sarcoma (shown) is a rare cancer of the blood vessels that is associated with HIV. It manifests as bluish-red oval-shaped patches that may eventually become thickened. Lesions may appear singly or in clusters.

38 Extensive tumor lesions of Kaposis s sarcoma in AIDS patient. Source: AIDS, 1997

39 CD4 T-cell dysfunction. Viral Coinfections 39

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41 HIV Disease Direct infection of organ systems HIV can directly infect the: Brain (HIV dementia) Gut (wasting) Heart (cardiomyopathy) DR. S.K CHATURVEDI

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43 AIDS Associated Disease Categories 1. Gastrointestinal: Cause most of illness and death of late AIDS. Symptoms: Diarrhea Wasting (extreme weight loss) Abdominal pain Infections of the mouth and esophagus. Pathogens: Candida albicans, cytomegalovirus, Microsporidia, and Cryptosporidia.

44 African AIDS patient with slim disease Source: Tropical Medicine and Parasitiology, 1997

45 AIDS Associated Disease Categories 2. Respiratory: 70% of AIDS patients develop serious respiratory problems. 3.Neurological: Symptoms many include: Headaches, peripheral nerve problems, and AIDS dementia complex 4. Skin and Mocusa 5. Eye

46 HIV Disease Progression of HIV disease is measured by: CD4+ count Degree of immune suppression Lower CD4+ count means decreasing immunity Viral load Amount of virus in the blood Higher viral load means more immune suppression DR. S.K CHATURVEDI

47 Progression of HIV Infection HIGH viral load (number of copies of HIV in the blood) LOW CD4 count (type of white blood cell) Increasing clinical symptoms (such as opportunistic infections) DR. S.K CHATURVEDI

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49 Diagnosis ELISA Western blot RT-PCR, qpcr (viral load) 49

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51 g p g p p 6 8 p 5 5 p 5 3 Spectrum of anti-hiv testing g p p 4 0 p 3 4 p 2 4 p 1 8 p 1 2 DNA PCR RNA PCR p24 Ag 3rd gen ELISA 1st gen ELISA Detuned ELISA early recent / established advanced 1wk 2wk 3wk 2mo 6mo 1yr 2yr 3yr +8yr

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53 Anti-HIV Strategies Education Chemotherapy Highly Active Anti Retroviral Therapy (HAART) 53

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Human Immunodeficiency Virus. Acquired Immune Deficiency Syndrome AIDS

Human Immunodeficiency Virus. Acquired Immune Deficiency Syndrome AIDS Human Immunodeficiency Virus Acquired Immune Deficiency Syndrome AIDS Sudden outbreak in USA of opportunistic infections and cancers in young men in 1981 Pneumocystis carinii pneumonia (PCP), Kaposi s