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HIV and AIDS All that we need to know !

HIV and AIDS All that we need to know !. HIV and AIDS. Natural History of HIV/AIDS An Update on HIV Infection. Dr.R.V.S.N.Sarma., M.D., M.Sc., Consultant Physician & Chest Specialist. visit us at www.drsarma.in. Web Resources Consulted. http://www.faetc.org/ http://www.cdc.gov/hiv/

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HIV and AIDS All that we need to know !

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  1. HIV and AIDS All that we need to know !

  2. HIV and AIDS Natural History of HIV/AIDS An Update on HIV Infection Dr.R.V.S.N.Sarma.,M.D., M.Sc., Consultant Physician & Chest Specialist visit us at www.drsarma.in

  3. Web Resources Consulted • http://www.faetc.org/ • http://www.cdc.gov/hiv/ • http://www.nacoonlone.com/ • http://www.aidsfreetn.com/ • http://www.aid-info.ch • http://www.avert.org/ • http://www.doh.state.fl.us/disease_ctrl/aids • http://www.apregistry.com • http://www.aidsinfo.nih.gov

  4. HIV and AIDS BURDEN OF ILLNESS

  5. Global estimates foradults and children as of 2005 end • People living with HIV • New HIV infections in 2005 • Deaths due to AIDS in 2005 40.3 million [36.7 – 45.3 million] 4.9 million [4.3 – 6.6 million] 3.1 million [2.8 – 3.6 million]

  6. Adults and children estimated to be living with HIV as of 2005 end Eastern Europe & Central Asia 1.6 million [990 000 – 2.3 million] Western & Central Europe 720 000 [570 000 – 890 000] North America 1.2 million [650 000 – 1.8 million] East Asia 870 000 [440 000 – 1.4 million] North Africa & Middle East 510 000 [230 000 – 1.4 million] Caribbean 300 000 [200 000 – 510 000] South & South-East Asia 7.4 million [4.5 – 11.0 million] Sub-Saharan Africa 25.8 million [23.8 – 28.9 million] Latin America 1.8 million [1.4 – 2.4 million] Oceania 74 000 [45 000 – 120 000] Total: 40.3 (36.7 – 45.3) million

  7. Estimated number of adults and childrennewly infected with HIV during 2005 Eastern Europe & Central Asia 270 000 [140 000 – 610 000] Western & Central Europe 22 000 [15 000 – 39 000] North America 43 000 [15 000 – 120 000] East Asia 140 000 [42 000 – 390 000] North Africa & Middle East 67 000 [35 000 – 200 000] Caribbean 30 000 [17 000 – 71 000] South & South-East Asia 990 000 [480 000 – 2.4 million] Sub-Saharan Africa 3.2 million [2.8 – 3.9 million] Latin America 200 000 [130 000 – 360 000] Oceania 8200 [2400 – 25 000] Total: 4.9 (4.3 – 6.6) million

  8. Estimated adult and child deaths from AIDS during 2005 Western & Central Europe 12 000 [<15 000] Eastern Europe & Central Asia 62 000 [39 000 – 91 000] North America 18 000 [9000 – 30 000] East Asia 41 000 [20 000 – 68 000] North Africa & Middle East 58 000 [25 000 – 145 000] Caribbean 24 000 [16 000 – 40 000] South & South-East Asia 480 000 [290 000 – 740 000] Sub-Saharan Africa 2.4 million [2.1 – 2.7 million] Latin America 66 000 [52 000 – 86 000] Oceania 3600 [1700 – 8200] Total: 3.1 (2.8 – 3.6) million

  9. About 14 000 new HIV infections a day in 2005 • More than 95% are in low & middle income countries • Almost 2000 are in children under 15 years of age • About 12 000 are in persons aged 15 to 49 years, • of whom almost 50% are women and • about 50% are 15–24 year olds

  10. HIV Estimates in India – end of 2003

  11. INDIAN Scenario as of 2003 end

  12. Tamilnadu’s Rank is Unique TAMILNADU IS THE HOT SEAT OF HIV & AIDS TAMILNADU IS THE HOT SEAT OF HIV & AIDS

  13. Male / Female Ratio of HIV in India

  14. HIV and AIDS THE TARGET OUR IMMUNE SYSTEM

  15. Our Manufacturing Plant- The Cell

  16. Military force of the body, B Cells and T cells Consists of lymphoid organs and tissues B and T-cells are from stem cells in the bone marrow B-cells recognize specific antigens and secrete Abs T cells have types T helpers (CD4), T Suppressors, K cells (CD8) The Normal immune system

  17. T-cells regulate the immune system Kill cells that bear specific target antigens CD4+ cells are helper T cells that CD4 activate B-cells, CD8 & macrophages Phagocytes include monocytes and macrophages The complement system consists of 25 proteins HIV attacks the military force & weakens the immunity The body succumbs to opportunistic infections (OIs) The Normal immune system

  18. OUR SCAVANGERS MACROPHAGE PSEUDOPODIA

  19. HIV and AIDS THE VIRUS

  20. HIV EM Photograph

  21. Antigens of HIV

  22. HIV-1 and HIV-2 • HIV-1 and HIV-2 • Transmitted through the same routes • Associated with similar opportunistic infections • HIV-1 is more common worldwide • HIV-2 is found primarily in West Africa, Mozambique and Angola.

  23. HIV-1 and HIV-2 Differences between HIV-1 and HIV-2 • HIV-2 is less easily transmitted. • HIV-2 develops more slowly. • HIV-2 cause less severe illness • MTCT is relatively rare with HIV-2. • HHV-6 does not cause AIDS – Helper virus

  24. HIV – The Demon virus !! • Its target is our immune system CD4 (Military force) • It makes us unfit to cope with even common pathogens • Long asymptomatic stage – ‘Carrier state’ – Gentle man • Not amenable easily to treatment with drugs • Treatment is expensive, not readily available, side effects • No readily available vaccine to protect before hand

  25. Kindness of HIV • Can’t survive long out side host cells • Larger volume needed for infecting (0.01ml v/s 0.00000001) • Can’t transmitted by air, water, food, casual contact, fomites • Easily destroyed by soap and antiseptics • Gives a long time before disease manifests – (implications) • Needs some ‘abnormal’ or ‘highly active’ life style to infect

  26. Viral Replication - Basic Concepts • Viruses are obligate intracellular parasites • Viruses carry their genome (RNA or DNA) and sometimes functional proteins required for early steps in replication cycle • Viruses depend on host cell machinery to complete replication cycle and must commandeer that machinery to successfully replicate

  27. Viral Replication - Basic Concepts • Replication cycle produces - Functional RNAs and proteins • Genomic RNA or DNA and structural proteins • 100s - 1,000s of new particles produced by each cycle • Referred to as burst size; Many are defective • End of ‘eclipse’ phase • Replication may be cytolytic or non-cytolytic

  28. Viral Attack on CD4 Attachment (First Step) • Surface protein on virus attaches to specific receptor (s) on cell surface • Virus specific receptor is necessary but not sufficient for viruses to infect cells and complete replication cycle

  29. Viral Receptors • CAR • CAR, CD55 • Integrin VLA-2, CD55 • CD21 • CD4, CCR5, CXCR4 • CD46 • Erythrocyte P Ag • Adenovirus • Coxsackie virus • Echovirus • Epstein-Barr Virus • HIV-1, HIV-2 • Measles virus • Parvo virus, Poliovirus

  30. CD4 Cell R5 HIV CCR5 CD4 CXCR4 HIV Cell Binding and Entry T HELPER CD4 CELL

  31. CD4 Cell R5 HIV CCR5 CD4 CXCR4 CCR5 Natural Ligand - Chemochines T HELPER CD4 CELL T HELPER CD4 CELL Chemochines Rantes MIP-1 Beta MIP-1 Alpha

  32. CD4 Cell R4 HIV CCR5 CD4 CXCR4 HIV Cell Binding and Entry T HELPER CD4 CELL T HELPER CD4 CELL

  33. CD4 Cell R4 HIV CCR5 CD4 CXCR4 SDF-1 SDF-1 - Natural Ligand For CXCR4 T HELPER CD4 CELL T HELPER CD4 CELL

  34. Retro-viral attachment to CCR5 Innate Immunity Acquired Immunity

  35. HIV attacking CD4 cell

  36. Viral Replication Penetration (Second Step) • Enveloped viruses penetrate cells through fusion of viral envelope with host cell membrane • May or may not involve receptor mediated endocytosis • Non enveloped viruses penetrate by - Receptor mediated endocytosis • Translocation of the virion across the host cell

  37. Viral Replication Multiplication (Third Step) • Replication of viral RNA occurs • This utilizes the DNA of host nucleus • Invaded CD4 cells genome is altered • They produce thousands of copies of HIV- RNA

  38. EM photo of CD4 with HIV infection

  39. Viral Replication Destruction (Fourth Step) • CD4 cells are over powered and destroyed • Instead of being defense machinery they • Are the seat of HIV replication • CD4 cells are destroyed – cytolysis • HIV copies are released to attack more CD4

  40. New HIV Budding from CD4

  41. HIV Life Cycle in CD4 Cell

  42. CD4 Cell Destruction

  43. HIV: Antiretroviral Therapy Nucleoside Analogue RTI Entry Inhibitors RT HIV RNA HIV DNA Nucleus HIV Protease Inhibitors Host Cell Non-Nucleoside RTI

  44. HIV Havoc in CD4 • HIV is a retrovirus that uses its RNA and the host’s DNA to make viral copy. It has a long incubation period. • HIV consists of a cylindrical center surrounded by a sphere-shaped lipid envelope. The center consists of two single strands of RNA • HIV causes severe damage to and eventually destroys the immune system by utilizing the DNA of CD4+ lymphocytes to replicate itself, destroying the CD4+ lymphocyte.

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