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Human Immunodeficiency virus Infection

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Human Immunodeficiency virus Infection

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Human Immunodeficiency virus Infection

  1. 1. Human Immunodeficiency Virus Infection Dr.T.V.Rao MD Dr.T.V.Rao MD
  2. 2. Beginning of HIV/AIDS <ul><li>The first published article related to AIDS was in 1981. The principal author’s name was Michael Gottlieb and it appeared in the Morbidity and Mortality Weekly Report for June 5th. This article reported that there was a random increase in pneumocystis carinii pneumonia (PCP), a rare lung infection. </li></ul>Dr.T.V.Rao MD
  3. 3. Discovery of HIV infection. <ul><li>In 1982, the term Acquired Immune Deficiency Syndrome is used for the first time. The name was designated by the CDC. </li></ul><ul><li>In 1983, French scientists at the Institute Pasteur found a new virus that they called lymphadenopathy-associated virus or LAV. About a year later, Dr. Robert Gallo, of the National Cancer institute discovered HLTV-III. The first discovery was made in France at the Institute Pasteur, but shared credit is given to Dr. Robert Gallo, the discoverer of AIDS and his French counterparts for discovering HIV on April 23, 1984. </li></ul>Dr.T.V.Rao MD
  4. 4. Dr. Luc Montagnier wins the Nobel Prize in Medicine in 2008 Dr.T.V.Rao MD
  5. 5. What is Human Immune Deficiency Virus <ul><li>Genus Retroviridae </li></ul><ul><li>Lentivirus, which literally means slow virus - it takes such a long time to develop adverse effects in the body. </li></ul><ul><li>This virus attacks the immune system </li></ul><ul><li>There are two strains – HIV 1 & HIV 2 </li></ul>Dr.T.V.Rao MD
  6. 6. What is Human Immune Deficiency Virus <ul><li>These contain RNA, the genetic material of HIV </li></ul><ul><li>The outer layer of the HIV virus cell is covered in coat proteins, which can bind to certain WBCs. This allows the virus to enter the cell, where it alters the DNA. </li></ul><ul><li>The virus infects and destroys the CD4 lymphocytes which are critical to the body’s immune response. </li></ul>Dr.T.V.Rao MD
  7. 7. History of HIV <ul><li>The HIV virus first came to light during the early 1980’s. </li></ul><ul><li>A number of healthy gay men in New York began to develop rare opportunistic infections & cancers, that were resistant to treatment. </li></ul><ul><li>One such viral opportunistic infection is cytomegalovirus that causes blindness & inflammation of the colon </li></ul>Dr.T.V.Rao MD
  8. 8. HIV Origins <ul><li>Research teams in the U.S.A & France made independent research discoveries of the virus. </li></ul><ul><li>French researchers discovered a virus linked to AIDS in 1983, they called it Lymphadenopathy-Associated Virus (LAV) </li></ul><ul><li>In 1984, American researchers isolated a virus that caused AIDS, calling it Human T-lymph tropic Virus type III (HTLV- III ) </li></ul><ul><li>These two viruses were later found to be the same virus - HIV </li></ul>Dr.T.V.Rao MD
  9. 9. HIV Origin <ul><li>The emergence of HIV & AIDS has resulted in countless debates as to where it originated from </li></ul><ul><li>It’s suspected that it originated from S.I.V (Simian Immunodeficiency Virus) </li></ul><ul><li>SIV affects Monkeys </li></ul>Dr.T.V.Rao MD
  10. 10. HIV Origins <ul><li>Certain strains of SIV closely resemble the two types of HIV </li></ul><ul><li>HIV 1 – was difficult to link with SIV </li></ul><ul><li>In 1999 SIVcpz closely related to HIV 1 </li></ul><ul><li>Originated from chimpanzees but it has significant differences from HIV-1 </li></ul><ul><li>HIV 2 closely related to SIVsm </li></ul><ul><li>Originated from the green monkey </li></ul>Dr.T.V.Rao MD
  11. 11. Dr.T.V.Rao MD
  12. 12. Family : Retroviridae Subfamily : Lentivirus <ul><li>RNA virus, 120nm in diameter </li></ul><ul><li>Envelope gp160; gp120 & gp41 </li></ul><ul><li>Icosahedral symmetry </li></ul><ul><li>Nucelocapsid </li></ul><ul><ul><li>Outer matrix protein (p17) </li></ul></ul><ul><ul><li>Major capsid protein (p24) </li></ul></ul><ul><ul><li>Nuclear protein (p7) </li></ul></ul><ul><li>Diploid RNA with several copies of reverse transcriptase </li></ul>Dr.T.V.Rao MD
  13. 13. Retroviral Genes <ul><li>gag (group-specific antigen): makes the cone shape viral capsid. </li></ul><ul><li>pol (polymerase): codes for viral enzymes reverse transcriptase, integrase, and viral protease. </li></ul><ul><li>env (envelope): makes surface protein gp120 and trans membrane gp41, enabling HIV to fuse to CD4 cells. </li></ul>Dr.T.V.Rao MD
  14. 14. Genes Coding Structural Proteins gag <ul><li>1 The gag gene – core and shell expressed as p55 – ( p18,- p17) cleaved as p15, p18,and p24 make up as viral core and shell </li></ul><ul><li>p24 seen during early stages reappearance in the late stages exacerbation of disease </li></ul>Dr.T.V.Rao MD
  15. 15. Envelop glycoprotein's env <ul><li>The env determines the synthesizes of envelop glycoprotein's gp160 cleaved into two envelop components gp120 which forms the surface spike and gp 41 which trans membrane protein. </li></ul><ul><li>The gp120 antibodies are present till the death of the patient. </li></ul>Dr.T.V.Rao MD
  16. 16. Polymerase reverse transcriptase pol <ul><li>The pol gene codes for the polymerase reverse transcriptase and other viral enzymes </li></ul><ul><li>Expressed as precursor protein which is cleaved into proteins p31, p51,and p66 </li></ul>Dr.T.V.Rao MD
  17. 17. <ul><li>Genome and Proteins of HIV </li></ul>Dr.T.V.Rao MD
  18. 18. Other genes <ul><li>Tat The Tran activator gene influences the function of genes some distance away. It controls transactivation of all HIV proteins. rev </li></ul><ul><li>The differential regulator of expression of virus protein genes. vif </li></ul><ul><li>The virus infectivity factor gene is required for infectivity as cell-free virus. nef </li></ul><ul><li>The negative regulator factor retards HIV replication. vpr </li></ul><ul><li>The virus protein R gene has an undetermined function.. </li></ul>Dr.T.V.Rao MD
  19. 19. Genes differ HIV I for HIV II <ul><li>vpu </li></ul><ul><li>The virus protein U gene is required for efficient viral replication and release. It is found only in HIV-1 . vpx </li></ul><ul><li>The virus protein X gene has an undetermined function. It is found only in HIV-2 and SIV. </li></ul>Dr.T.V.Rao MD
  20. 20. Types of HIV Dr.T.V.Rao MD
  21. 21. Dr.T.V.Rao MD
  22. 22. Subtype C is Major type in India <ul><li>Subtype C is predominant in Southern and East Africa, India and Nepal. It has caused the world's worst HIV epidemics and is responsible for around half of all infections. </li></ul>Dr.T.V.Rao MD
  23. 23. Resistance <ul><li>The virus are inactivated in 10 minutes at 60 0 c and in seconds at 100 0 c </li></ul><ul><li>At room temperature survive for seven days </li></ul><ul><li>HIV are inactivated in 10 minutes by treatment with 50% ethanol </li></ul><ul><li>35% Isopropanol. </li></ul><ul><li>0.5% Lysol and paraformaldehyde </li></ul><ul><li>0.3% hydrogen </li></ul><ul><li>10% house hold bleach </li></ul><ul><li>Hypochlorite solution at 0.5% </li></ul><ul><li>2% Glutaraldehyde </li></ul>Dr.T.V.Rao MD
  24. 24. HIV Replication <ul><ul><li>Attachment </li></ul></ul><ul><ul><li>Penetration </li></ul></ul><ul><ul><li>Uncoating </li></ul></ul><ul><ul><li>Reverse Transcription </li></ul></ul><ul><ul><li>Integration </li></ul></ul><ul><ul><li>Replication </li></ul></ul><ul><ul><li>Assembly </li></ul></ul><ul><ul><li>Release </li></ul></ul>Dr.T.V.Rao MD
  25. 25. <ul><li>Life Cycle of HIV </li></ul><ul><ul><li>1. Attachment: Virus binds to surface molecule (CD4) of T helper cells and macrophages. </li></ul></ul><ul><ul><ul><li>Coreceptors : Required for HIV infection. </li></ul></ul></ul><ul><ul><ul><li>CXCR4 and CCR5 mutants are resistant to infection. </li></ul></ul></ul><ul><ul><li>2. Fusion : Viral envelope fuses with cell membrane, releasing contents into the cell. </li></ul></ul>Dr.T.V.Rao MD
  26. 26. HIV Life Cycle: Attachment Requires CD4 Receptor plus a Coreceptor Dr.T.V.Rao MD
  27. 27. <ul><li>The HIV receptor </li></ul><ul><li>Gp160 is composed of gp41 and gp120 and forms the receptor for binding to the host cell (CD4 positive cells). </li></ul><ul><li>The gp41 portion is half embedded in the membrane envelope and interacts with gp120 portion on the exterior side of the membrane. </li></ul><ul><li>Each receptor is composed of 3 subunits of gp41 and 3 subunits of gp120. </li></ul>Dr.T.V.Rao MD
  28. 28. The HIV Receptor Dr.T.V.Rao MD
  29. 29. <ul><li>Lifecycle of HIV </li></ul><ul><li>HIV particles enter the body in a fluid as it can not survive without a support medium. </li></ul><ul><li>The virus targets any cell expressing CD4, including T helper cells, macrophages, dendritic cells and monocytes. </li></ul>Dr.T.V.Rao MD
  30. 30. <ul><li>Life Cycle of HIV </li></ul><ul><ul><li>3. Reverse Transcription: Viral RNA is converted into DNA by unique enzyme reverse transcriptase . </li></ul></ul><ul><ul><li>Reverse transcriptase </li></ul></ul><ul><ul><li>RNA ---------------------> DNA </li></ul></ul><ul><ul><li>Reverse transcriptase is the target of several HIV drugs: AZT, ddI, and ddC. </li></ul></ul>Dr.T.V.Rao MD
  31. 31. Dr.T.V.Rao MD
  32. 32. Infection spread throughout the Body <ul><li>Within the inflammatory cells of the infection (T cells) </li></ul><ul><li>Site of replication shifts to lymphoid tissues: </li></ul><ul><li>Lymph nodes </li></ul><ul><li>Spleen </li></ul><ul><li>Liver </li></ul><ul><li>Bone marrow </li></ul><ul><li>Macrophages and Langerhans cells become reservoirs and sites of </li></ul><ul><li>replication but do not die themselves. </li></ul>Dr.T.V.Rao MD
  33. 33. Effects of HIV on the immune system <ul><li>3 areas: </li></ul><ul><li>1. Destruction of CD4+ T cells population </li></ul><ul><li>2. Immune effects due to HIV infection </li></ul><ul><li>3. Progression of HIV infection to AIDS </li></ul>Dr.T.V.Rao MD
  34. 34. <ul><li>2.Host’s immune responses </li></ul><ul><li>Both humoral and cell-mediated immune responses partially control the viral production but in this process they destroy the infected CD4+T cells, leading to a gradual decline of CD4+ T cells </li></ul><ul><li>HIV-specific CTLs kill infected CD4+ T cells </li></ul><ul><li>Antibodies that recognize a variety of HIV antigens are produced - Antibody dependent cell-mediated cytotoxicity </li></ul><ul><li>Apoptosis of infected cells </li></ul>Dr.T.V.Rao MD
  35. 35. Blood and Body fluids contain High concentration of Viral particles <ul><li>Blood </li></ul><ul><li>Semen/Vaginal fluids (as high as blood) </li></ul><ul><li>Breast milk </li></ul><ul><li>Pus from sores </li></ul>Dr.T.V.Rao MD
  36. 36. Low concentrations of HIV <ul><li>It is highly unlikely you will be infected if you come into contact with: </li></ul><ul><li>Sweat </li></ul><ul><li>Tears </li></ul><ul><li>Urine </li></ul><ul><li>Saliva (-highly possible if blood from mouth sores is present) </li></ul>Dr.T.V.Rao MD
  37. 37. High Risk Populations: <ul><li>Males, homosexuals & bisexuals </li></ul><ul><li>IV drug users </li></ul><ul><li>Improperly screened transfusion recipients </li></ul><ul><li>4. Sexual partners of persons infected with HIV </li></ul><ul><li>5. Infants of HIV –infected mothers </li></ul>Dr.T.V.Rao MD
  38. 38. How is HIV Spread? <ul><li>ANY type of sexual activity (highest risk ) </li></ul><ul><li>Sharing used drug needles </li></ul><ul><li>Pregnancy-from mother to child </li></ul><ul><li>Sharing razors- if blood is present </li></ul><ul><li>Kissing- if even the smallest amount of blood is present. (-membranes of mouth are thin enough for HIV to enter straight into the body.) </li></ul><ul><li>Tattoos/body piercing if equipment is not clean. </li></ul>Dr.T.V.Rao MD
  39. 39. HIV in Body Fluids Semen 11,000 Vaginal Fluid 7,000 Blood 18,000 Amniotic Fluid 4,000 Saliva 1 Average number of HIV particles in 1 ml of these body fluids Dr.T.V.Rao MD
  40. 40. Transmission <ul><li>Vaginal Intercourse </li></ul><ul><li>Anal Intercourse (10x higher infection rate than vaginal intercourse because of tissue tear is higher </li></ul><ul><li>Oral Intercourse </li></ul><ul><li>Blood Transfusion (risk greater than 90% if sample is already infected) </li></ul><ul><li>Needles (tattoos, injections) </li></ul><ul><li>Infected mother to the infant through: </li></ul><ul><li>Pregnancy (placenta), Birth, and breastfeeding </li></ul>Dr.T.V.Rao MD
  41. 41. Window Period <ul><li>This is the period of time after becoming infected when an HIV test is negative </li></ul><ul><li>90 percent of cases test positive within three months of exposure </li></ul><ul><li>10 percent of cases test positive within three to six months of exposure </li></ul>Dr.T.V.Rao MD
  42. 42. Pathogenesis of HIV / AIDS Infected T-Cell HIV Virus T-Cell HIV Infected T-Cell New HIV Virus Dr.T.V.Rao MD
  43. 43. <ul><li>Immune responses fail to eradicate all viruses. </li></ul><ul><li>Viral load is maintained at low level </li></ul><ul><li>Continuous decline of CD4+ T cells </li></ul>Dr.T.V.Rao MD
  44. 44. Immune defects due to HIV infection <ul><li>B cells – impaired humoral response </li></ul><ul><li>B-cell hyper reactivity </li></ul><ul><li>Polyclonal hypergammaglobulinemia due to enhanced nonspecific IgG and IgA production. </li></ul><ul><li>Impaired Ab-isotype switching and inability to respond to specific antigen. </li></ul><ul><li>High incidence of B-cell lymphomas </li></ul><ul><li>Lymph nodes </li></ul><ul><li>HIV kills cells in the lymph nodes </li></ul><ul><li>Early HIV infection: destruction of dendritic cells </li></ul><ul><li>Late stage: extensive damage, tissue necrosis, a loss of follicular dendritic cells and germinal centres. </li></ul><ul><li>An inability to trap Ag or support activation of T+B cells </li></ul>Dr.T.V.Rao MD
  45. 45. CDC Classification of HIV <ul><li>Category 1: > 500 cells/mm3 (or CD4% > 28%) </li></ul><ul><li>Category 2: 200-499 cells/mm3 (or CD4% 14% - </li></ul><ul><li>28%) </li></ul><ul><li>Category 3: < 200 cells/mm3 (or CD4% < 14%)(CD4+ T-lymphocyte counts per microliter of blood) </li></ul>Dr.T.V.Rao MD
  46. 46. Progression of HIV infection <ul><li>After initial infection with HIV, there is usually an acute flu-like illness. </li></ul><ul><li>This illness may include </li></ul><ul><li>Fever </li></ul><ul><li>Headache </li></ul><ul><li>Tiredness </li></ul><ul><li>Enlarged lymph nodes </li></ul><ul><li>But after this most individuals are clinically asymptomatic for years. This is called the clinical latency period. </li></ul>normal Severely impaired Abnormal Slightly reduced Time Acute HIV disease Exposure to HIV Clinical latency period -declining CD4+ T cell amount AIDS Immune competence Opportunistic infections Progression of HIV infection Dr.T.V.Rao MD
  47. 47. WHO clinical case definition for AIDS in South-East Asia <ul><li>WHO clinical case definition for AIDS in South-East Asia Clinical AIDS in an adult is defined as an individual who has been identified as meeting the two criteria A and B below: A. Positive test for HIV infection by two tests based on preferably two different antigens. B. Any one of the following criteria: </li></ul><ul><li>- Weight loss of 10% body weight or cachexia, not known to be due to a condition unrelated to HIV infection - Chronic diarrhoea of one month's duration, intermittent or constant </li></ul>Dr.T.V.Rao MD
  48. 48. WHO clinical case definition for AIDS in South-East Asia <ul><li>Disseminated, miliary or extra pulmonary tuberculosis </li></ul><ul><li>Candidiasis of the oesophagus; diagnosable as dysphasia, odynophagia and oral Candidiasis </li></ul><ul><li>Neurological impairment restricting daily activities, not known to be due to a condition unrelated to HIV (e.g. trauma) </li></ul><ul><li>Kaposi's sarcoma. </li></ul>Dr.T.V.Rao MD
  49. 49. Stage 1 - Primary <ul><li>Short, flu-like illness - occurs one to six weeks after infection </li></ul><ul><li>no symptoms at all </li></ul><ul><li>Infected person can infect other people </li></ul>Dr.T.V.Rao MD
  50. 50. Stage 2 - Asymptomatic <ul><li>Lasts for an average of ten years </li></ul><ul><li>This stage is free from symptoms </li></ul><ul><li>There may be swollen glands </li></ul><ul><li>The level of HIV in the blood drops to very low levels </li></ul><ul><li>HIV antibodies are detectable in the blood </li></ul>Dr.T.V.Rao MD
  51. 51. Stage 3 - Symptomatic <ul><li>The symptoms are mild </li></ul><ul><li>The immune system deteriorates </li></ul><ul><li>Emergence of opportunistic infections and cancers </li></ul>Dr.T.V.Rao MD
  52. 52. Stage 4 - HIV  AIDS <ul><li>The immune system weakens </li></ul><ul><li>The illnesses become more severe leading to an AIDS diagnosis </li></ul>Dr.T.V.Rao MD
  53. 53. Progression to AIDS <ul><li>During the latency period, lymph nodes and the spleen are sites of continuous HIV replication and cell destruction. </li></ul><ul><li>The immune system remains competent at handling most infections with opportunistic microbes but the number of CD4+ T cells steadily declines. </li></ul><ul><li>Symptoms often experienced months to years before the onset of AIDS. </li></ul><ul><li>Lack of energy </li></ul><ul><li>Weight loss </li></ul><ul><li>Frequent fevers and sweats </li></ul><ul><li>Persistent or frequent yeast infections </li></ul><ul><li>Persistent skin rashes </li></ul><ul><li>Dysfunction of CNS </li></ul>Dr.T.V.Rao MD
  54. 54. <ul><li>Final stage of HIV infection - AIDS </li></ul><ul><li>Occurs when the destruction of peripheral lymphoid tissue is complete and the blood CD4+ T cell count drops below 200 cells/mm 3 . (Healthy adults usually have CD4+ T-cell counts of 1,000 or more). </li></ul><ul><li>AIDS – acquired immunodeficiency syndrome – is marked by development of various opportunistic infections and malignancies. </li></ul><ul><li>The level of virus in the blood and CD4+ T cell count can predict the risk of developing AIDS. V oral titers often accelerate as the patient progresses towards AIDS. </li></ul><ul><li>Without treatment, at least 50% of people infected with HIV will develop AIDS within ten years. </li></ul>Progression to AIDS Dr.T.V.Rao MD
  55. 55. Mother-to-Baby <ul><li>Before Birth </li></ul><ul><li>During Birth </li></ul><ul><li>Postpartum </li></ul><ul><ul><li>After the birth </li></ul></ul>Dr.T.V.Rao MD
  56. 56. How is HIV not spread? <ul><li>Shaking hands </li></ul><ul><li>Hugging </li></ul><ul><li>Swimming pools </li></ul><ul><li>Toilet seats </li></ul><ul><li>Insect bites </li></ul><ul><li>Donating blood </li></ul>Dr.T.V.Rao MD
  57. 57. THE NATIONAL HIV TESTING POLICY <ul><li>No individual should be made to undergo a mandatory testing for HIV </li></ul><ul><li>No mandatory HIV testing should be imposed as a precondition for </li></ul><ul><li>- Employment </li></ul><ul><li>- Providing health care services and facilities </li></ul><ul><li>Any HIV testing must be accompanied by a pretest and posttest counseling services </li></ul><ul><li>(through VCTC) </li></ul><ul><li>Testing without consent – hindrance to the control of the epidemic </li></ul>Dr.T.V.Rao MD
  58. 58. Counseling Dr.T.V.Rao MD
  59. 59. Pre-test Counseling explain to individuals <ul><li>Transmission </li></ul><ul><li>Prevention </li></ul><ul><li>Risk Factors </li></ul><ul><li>Voluntary & Confidential </li></ul><ul><li>Report ability of Positive Test Results </li></ul>Dr.T.V.Rao MD
  60. 60. Post-test Counseling <ul><li>Clarifies test results </li></ul><ul><li>Need for additional testing </li></ul><ul><li>Promotion of safe behavior </li></ul><ul><li>Release of results </li></ul>Dr.T.V.Rao MD
  61. 61. Three types of tests <ul><li>(i) Screening tests - ELISA and simple/rapid tests. </li></ul><ul><li>(ii) Confirmatory or supplemental tests- </li></ul><ul><li>Western Blot assay. </li></ul><ul><li>(iii) Nucleic acid and antigen screening tests. Polymerase chain reaction (PCR), Ligase chain reaction (LCR), Nucleic acid based Sequence assays (NASBA) and some ELISA tests. </li></ul>Dr.T.V.Rao MD
  62. 62. Diagnosis of HIV <ul><li>Initial test for HIV is an indirect ELISA test </li></ul><ul><li>Economic, rapid, performed easily, high sensitivity and specificity </li></ul><ul><li>Detects anti-HIV antibodies in patient serum </li></ul><ul><li>Antibodies are generally detectable within 3 months of infection </li></ul><ul><li>Antibodies are typically directed at the envelope glycoproteins (gp120 and gp41) </li></ul>Dr.T.V.Rao MD
  63. 63. Absence of Antibodies to do not confirm absence of HIV infection <ul><li>Absence of antibody, as in ‘window period’ does not exclude the presence of the virus which can be detected by PCR amplification approx. ten days after infection </li></ul><ul><li>‘ Window period’ – time between infection and detection of serological viral marker </li></ul><ul><li>Direct ELISA for p24 antigen can also be used although the false negative rate is higher </li></ul>Dr.T.V.Rao MD
  64. 64. EIA/ELISA Test Positive Negative Run IFA Confirmation Repeat Positive Positive End Testing Repeat ELISA Every 3 months for 1 year Negative Positive Negative Indeterminate Repeat at 2-4 months Repeat at 3 weeks HIV Testing No HIV Exposure Low Risk HIV Exposure High Risk Negative HIV + Repeat every 6 months for continued High risk behavior Dr.T.V.Rao MD
  65. 65. Diagnosis of HIV <ul><li>Positive or indeterminate ELISA tests for anti-HIV antibodies are confirmed by immunoblotting (Western Blotting) which identifies specific HIV virus proteins </li></ul><ul><li>PCR can also be used </li></ul><ul><li>Detects pro-viral DNA or viral RNA </li></ul><ul><li>It is highly sensitive and specific but is more costly than ELISA </li></ul><ul><li>Can be used to test infants born to HIV-infected mothers </li></ul>Dr.T.V.Rao MD
  66. 66. Indirect ELISA test Dr.T.V.Rao MD
  67. 67. Western blot Test <ul><li>Confirms HIV infection </li></ul><ul><li>Proteins are separated by electrophoresis and transferred to a nitrocellulose membrane by the passage of an electric current </li></ul><ul><li>The proteins are treated with antibodies </li></ul><ul><li>Similar to ELISA technique, addition of secondary antibodies with an enzyme attached allows the use of colour to detect a particular protein </li></ul>Dr.T.V.Rao MD
  68. 68. Western Blotting <ul><li>A discrete protein band represents the specific antigen that the antibody recognizes </li></ul><ul><li>The bands from a positive Western blot are from antibodies binding to specific proteins and glycoprotein's from the HIV virus </li></ul><ul><li>The CDC recommends that the blot should be positive for two of the p24, gp41 and gp120/160 markers (gp160 is the precursor form of gp41 and gp120, the envelope protein) </li></ul>Dr.T.V.Rao MD
  69. 69. HIV Western blot Dr.T.V.Rao MD
  70. 70. Rapid Tests <ul><li>ADVANTAGES: </li></ul><ul><li>quicker to perform </li></ul><ul><ul><li>do not require batching </li></ul></ul><ul><ul><li>do not require specialised equipment or trained personnel </li></ul></ul><ul><ul><li>results delivered on the same day </li></ul></ul><ul><li>Only ‘WHO recommended’ Rapid HIV antibody tests should be used to ensure quality. </li></ul>Dr.T.V.Rao MD
  71. 71. The ‘Window period’ Aware of it <ul><li>Follows acute infection with HIV, before HIV antibodies can be detected in the patient’s blood stream. </li></ul><ul><li>Patient is highly infectious , despite testing HIV antibody negative, HIV is replicating rapidly in all body compartments. </li></ul><ul><li>Typically up to 12 weeks duration but may be shorter in more sensitive HIV antibody assays. </li></ul>Dr.T.V.Rao MD
  72. 72. Paediatric HIV Testing <ul><li>Infants born to HIV infected mothers will have antibodies to HIV in their serum as a result of: </li></ul><ul><ul><li>maternal-fetal transfer during pregnancy </li></ul></ul><ul><ul><li>delivery </li></ul></ul><ul><ul><li>breast-feeding </li></ul></ul><ul><li>they may not necessarily be infected ! </li></ul>Dr.T.V.Rao MD
  73. 73. Treatment of HIV <ul><li>Eradication of HIV infection not possible with currently available drugs </li></ul><ul><li>Viral replication can not be completely suppressed </li></ul><ul><li>Latently infected CD4+ T cells established at early stage </li></ul><ul><li>Goals of antiretroviral therapy are to: </li></ul><ul><li>- Suppress viral replication </li></ul><ul><li>- Restore and/or preserve immune function </li></ul><ul><li>- Improve quality of life </li></ul><ul><li>- Reduce HIV-associated morbidity and mortality </li></ul><ul><li>Combinations of antiretroviral drugs are used </li></ul><ul><li>Referred to as HAART (highly active antiretroviral therapy) </li></ul><ul><li>Suppress levels of plasma viraemia for long periods </li></ul><ul><li>Plasma viraemia is a strong prognostic factor in HIV infection </li></ul>Dr.T.V.Rao MD
  74. 74. Antiretroviral Drugs <ul><li>Significant declines in AIDS related morbidity and mortality are seen as a result of HAART </li></ul><ul><li>Several strategies for development of effective antiviral drugs </li></ul><ul><li>Potential therapies based on knowledge of the way in which HIV gains access into the cells and its method of replication </li></ul><ul><li>Targets for therapeutic anti-retroviral drugs: </li></ul><ul><li>- Inhibiting reverse transcription </li></ul><ul><li>- Inhibiting proteases </li></ul><ul><li>- Inhibiting integrate – interferes with integration of viral DNA into host genome </li></ul><ul><li>- Inhibiting fusion – prevents virus from fusing with host cell </li></ul>Dr.T.V.Rao MD
  75. 75. Therapeutic Options <ul><li>Combination of RT inhibitors protease inhibitors results in potent anti-viral activity </li></ul><ul><li>In most cases, two nucleoside analogues and one protease inhibitor are taken together </li></ul><ul><li>HAART lowers plasma viral loads in many cases to levels not detectable by current methods </li></ul><ul><li>Has improved the health of AIDS patients to the point that they can function at a normal level </li></ul>Dr.T.V.Rao MD
  76. 76. AIDS (Pregnancy & AIDS) <ul><li>Zidovudine(AZT) – recommended for px of maternal fetal HIV transmission & adm after 14mg AOG (PO meds); IVIT during labor; w/ neonate post birth for 6 wks. </li></ul><ul><li>Postpartum –monitor for s/of infxn place mother in isolation if mother is immune suppressed. </li></ul><ul><li>-restrict breastfeeding –infant/neonate is seen by physician at birth, 1 wk. or 2 wks., a mos., 2 mos., & 4 mos. of life </li></ul><ul><li>* Neonate- asymptomatic for 1 st several yrs. Of life & monitored for early sign of immunodeficiency </li></ul>Dr.T.V.Rao MD
  77. 77. Antiretroviral Drugs <ul><li>Nucleoside Reverse Transcriptase inhibitors </li></ul><ul><ul><li>AZT (Zidovudine) </li></ul></ul><ul><li>Non-Nucleoside Transcriptase inhibitors </li></ul><ul><ul><li>Viramune (Nevirapine) </li></ul></ul><ul><li>Protease inhibitors </li></ul><ul><ul><li>Norvir (Ritonavir) </li></ul></ul>Dr.T.V.Rao MD
  78. 78. Prevention and control of HIV <ul><li>Education </li></ul><ul><li>Prevention of blood born HIV transmission </li></ul><ul><li>Anti Retro Viral treatment </li></ul><ul><li>Combination therapy </li></ul><ul><li>Post exposure prophylaxis </li></ul><ul><li>Specific prophylaxis </li></ul><ul><li>Primary health care </li></ul>Dr.T.V.Rao MD
  79. 79. HIV Occupational Exposure <ul><li>Review facility policy and report the incident </li></ul><ul><li>Medical follow-up is necessary to determine the exposure risk and course of treatment </li></ul><ul><li>Baseline and follow-up HIV testing </li></ul><ul><li>Four week course of medication initiated one to two hours after exposure </li></ul><ul><li>AZT (200mg)-TID +lamivudine(3TC)(150mg)BID x 4days </li></ul><ul><li>Nelfinavir (750 mg) TID ,AZT/3TC </li></ul><ul><li>Exposure precautions practiced </li></ul>Dr.T.V.Rao MD
  80. 80. HIV Non-Occupational Exposure <ul><li>No data exists on the efficacy of antiretroviral medication after non-occupational exposures </li></ul><ul><li>The health care provider and patient may decide to use antiretroviral therapy after weighing the risks and benefits </li></ul><ul><li>Antiretroviral should not be used for those with low-risk transmissions or exposures occurring more than 72 hours after exposure </li></ul>PREVENTION --- FIRST Dr.T.V.Rao MD
  81. 81. Play safe <ul><li>Use the common sense </li></ul><ul><li>Be faithful to one partner, Use Condom. </li></ul><ul><li>Antiretroviral drugs </li></ul><ul><li>Caesarean deliv ery </li></ul>Dr.T.V.Rao MD
  82. 82. Abstinence <ul><li>It is the only 100 % effective method of not acquiring HIV/AIDS. </li></ul><ul><li>Refraining from sexual contact: oral, anal, or vaginal. </li></ul><ul><li>Refraining from intravenous drug use </li></ul>Dr.T.V.Rao MD
  83. 83. Monogamous relationship <ul><li>A mutually monogamous (only one sex partner) relationship with a person who is not infected with HIV </li></ul><ul><li>HIV testing before intercourse is necessary to prove your partner is not infected </li></ul>Dr.T.V.Rao MD
  84. 84. Sex Education – Best option to Prevent AIDS Move from Past to Future Dr.T.V.Rao MD
  85. 85. World AIDS Day , <ul><li>World AIDS Day , observed December 1 each year, is dedicated to raising awareness of the AIDS pandemic caused by the spread of HIV infection. It is common to hold memorials to honour persons who have died from HIV/AIDS on this day. Government and health officials also observe the event, often with speeches or forums on the AIDS topics. </li></ul>Dr.T.V.Rao MD
  86. 86. Do not Discriminate AIDS Patients Dr.T.V.Rao MD
  87. 87. <ul><li>Created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World </li></ul><ul><li>Email </li></ul><ul><li>[email_address] </li></ul>Dr.T.V.Rao MD

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