Nursing care for patients with immune disorders.pptx

Ppt

1. Nursing care for patients with immune disorders 1

2. Learning objectives At the end of this module, you will be able to: Describe the body’s general response Differentiate between cellular and humoral response Describe the difference between HIV infection and AIDS Discuss the HIV epidemics globally, regionally, and locally in terms of number of people affected Define the terms: antibody and antigen Uses assessment parameters for determining status of the immune system Explain how “window period” may affect HIV testing results Describe the progression of HIV infection 2

3. Immunity Immunity : is the ability of the body to defend itself against infectious agents. Immunology: is the study of the body defense mechanism against foreign invading agents Immunity is essential for survival: a . Defends us from bacteria, virus, and other pathogens 3

4. Immunity cont’d b. Detects abnormal cells that periodically develop in life and destroy them (e.g., cancer cells, tumor cells etc ) c . Ability to recognize non-self substances from self one’s Types of immunity i . Nonspecific immunity (innate immunity) ii. Specific immunity(Acquired or Adaptive Immunity) 4

5. Innate (Nonspecific) Immunity Non-specific is the 1 st line of defense. It distinguishes self antigen from non-self, but does not distinguish one type of pathogen from another. It can kill all types of pathogens. Defense is inborn or natural, thus it does not need to be exposed to the invader Both external and internal defense 5

6. Innate immunity cont’d External Skin Physical barrier to penetration by pathogens; secretions contain lysozyme (enzyme that destroys bacteria) Digestive tract High acidity of stomach protection by normal bacterial population of colon 6

7. Innate immunity cont’d Respiratory tract Secretion of mucus movement of mucus by cilia alveolar macrophages Genitourinary tract Acidity of urine vaginal lactic acid 7

8. Innate immunity cont’d Internal Phagocytic cells Ingest and destroy bacteria, cellular debris, denatured proteins, and toxins Interferons Inhibit replication of viruses Complement proteins promote destruction of bacteria enhance inflammatory response 8

9. Innate immunity cont’d Endogenous pyrogen Secreted by leukocytes and other cells; produces fever Natural killer (NK) cells Destroy cells infected with viruses, tumor cells, and mismatched transplanted tissue cells Mast cells Release histamine and cytokines that promote adaptive immunity 9

10. Acquired immunity Acquired immunity involves destruction of foreign invading organisms by specifically producing sensitized lymphocytes or antibodies Lymphocytes are key players in acquired immunity. Types of Acquired Immunity Cell mediated immunity Humoral (antibody mediated immunity) Both types of acquired immunity are initiated by antigens Immunization induces acquired immunity 10

11. Acquired immunity cont’d Antigens: are gchemical substances (proteins, lipoproteins, polysaccharides) located on the surfaces of foreign bodies are capable of inducing antibody production or sensitized lymphocytes in the host body. E.g. Antigens can be bacteria, virus, protozoan's, parasites, insect venoms, pollen, transplanted organ 11

12. Acquired immunity cont’d Lymphocytes in acquired immunity T-lymphocytes(helper T-cells, cytotoxicT-cells, suppressor T-cells) is responsible for “cell-mediated” immunity ii. B-lymphocytes is responsible for forming antibodies that provide “humoral” immunity. 12

13. Types of T cells and their function 1. helper T cells, 2 . cytotoxic T cells, and 3 . suppressor T cells. Helper T-cell(CD4+) most numerous of the T cells(3/4 th ) serve as the major regulator of virtually all immune functions 13

14. Helper T-cell cont’d When activated by antigens helper T-cells produces protein mediators, called lymphokines, that act on other cells of the immune system Among the important lymphokines secreted by the helper T cells are the following: Interleukin-2 Interleukin-3 14

15. Helper T-cell cont’d Interleukin-4 Interleukin-5 Interleukin-6 Granulocyte-monocyte colony-stimulating factor Interferon-gamma In the absence of the lymphokines from the helper T cells, the remainder of the immune system is almost paralyzed. 15

16. Helper T-cell cont’d acquired immunodeficiency syndrome (AIDS) virus, inactivate or destroy helper T-cells interleukin-2 stimulate both cytotoxic and suppressor T cells & helper T-cells themselves interleukins 4, 5, and 6 stimulate the B-lymphocyte Lymphokines activate the macrophages to cause far more efficient phagocytosis 16

17. Helper T-cell cont’d Summary of functions of Helper T-cells Stimulation of T- Cytotoxic and T- suppressor cells Stimulation of B-cells to form plasma cells Activation of the macrophage system etc. 17

18. Cytotoxic T(CD8+) Cells is a direct-attack cell capable of killing micro-organisms also called killer cells. it kill invaders by direct attack through the following methods: 1. They bore a hole through the membrane, so that electrolytes and fluid enters and burst the microbes 2. They release toxic substances and kill invaders 18

19. Cytotoxic T-cells cont’d The cytotoxic cells also play an important role in destroying cancer cells, heart transplant cells Viral infected cells other types of cells that are foreign to the person’s own body. 19

20. Suppressor T cells Prevent the cytotoxic cells from causing excessive immune reactions that might be damaging to the body’s own tissues(immune tolerance) 20

21. Cell mediated immunity It is the responsibility of the T-lymphocytes The T-lymphocytes get activated when they are exposed to antigen The antigen is presented to the T-lymphocytes by antigen presenting cells(APC) when exposed to antigen, the T lymphocytes proliferate and release large numbers of activated, specifically reacting T cells. 21

22. Cell mediated immunity cont’d Antigen presenting cells(APCs) The three major types of antigen-presenting cells are macrophages, B lymphocytes, and dendritic cells. The APC phagocytize antigens and partially broke it down into smaller peptide fragments The resulting digested fragments then bind to major histocompatability complex(MHC) proteins inside the APCs. 22

23. The fragment-MHC complex is then transported to the cell surface of APCs. helper T cell binds to this complex and get activated. The MHC proteins are encoded by a large group of genes called the major histocompatibility complex (MHC). 23

24. Health History The history should note the patient’s age along with information about past and present conditions and events that may provide clues to the status of the patient’s immune system. 24

25. Assessing for Immune Dysfunction Be alert for the following signs and symptoms: Respiratory System Changes in respiratory rate Cough (dry or productive) Abnormal lung sounds (wheezing, crackles, rhonchi) Rhinitis Hyperventilation Bronchospasm Cardiovascular System Hypotension Tachycardia Dysrhythmia Vasculitis Anemia Gastrointestinal System Hepatosplenomegaly Colitis Vomiting Diarrhea 25

26. Genitourinary System Frequency and burning on urination Hematuria Discharge Musculoskeletal System Joint mobility, edema, and pain Skin Rashes Lesions Dermatitis Hematomas or purpura Edema or urticaria Inflammation Discharge Neurosensory System Cognitive dysfunction Hearing loss Visual changes Headaches and migraines Ataxia Tetany 26

27. Physical Assessment On physical examination the skin and mucous membranes are assessed for lesions, dermatitis, purpura (subcutaneous bleeding), urticaria , inflammation, orany discharge. Any signs of infection are noted. The patient’s temperature is recorded, and the patient is observed for chills and sweating. 27

28. The anterior and posterior cervical, axillary, and inguinal lymph nodes are palpated for enlargement; if palpable nodes are detected, their location, size, consistency, and reports of tenderness on palpation are noted. Joints are assessed for tenderness, swelling, increased warmth, and limited range of motion. The patient’s respiratory, cardiovascular, genitourinary, gastrointestinal, and neurosensory systems are evaluated for signs and symptoms indicative of immune dysfunction. Any functional limitations or disabilities the patient may have are also assessed. 28

29. Diagnostic Evaluation A series of blood tests and skin tests and a bone marrow biopsy may be performed to evaluate the patient’s immune competence. Various laboratory tests may be performed to assess immune system activity or dysfunction. The studies assess leukocytes and lymphocytes, humoral immunity, cellular immunity, phagocytic cell function, complement activity, hypersensitivity reactions, specific antigen–antibodies, or human immunodeficiency virus (HIV) infection. 29

30. Humoral (Antibody-mediated) Immunity Tests B-cell quantification with monoclonal antibody In vivo immunoglobulin synthesis with T-cell subsets Specific antibody response Total serum globulins and individual immunoglobulins (electrophoresis, immunoelectrophoresis, single radial immuneodiffusion, nephelometry, and isohemagglutinin techniques). 30

31. Cellular (Cell-mediated) Immunity Tests Total lymphocyte count T-cell and T-cell-subset quantification with monoclonal antibody Delayed hypersensitivity skin test Cytokine production Lymphocyte response to mitogens, antigens, and allogenic cells Helper and suppressor T-cell functions 31

32. Autoimmune Diseases When the immune system attacks the body's own cells, it produces an autoimmune disease. Some examples of autoimmune diseases include: Type I diabetes attacks insulin-producing cells. Rheumatoid arthritis attacks connective tissues around joints. Myasthenia gravis attacks neuromuscular junctions. Multiple sclerosis (MS) destroys functions of brain and spinal cord neurons. Some autoimmune diseases are treated with medications that alleviate specific symptoms.

33. Immunological Problems & Diseases There are several ways in which the immune system may fail : When the pathogen is too violent (multiplies too fast, causes too much damage), or evades the immune system (e.g., via mutation). Solution: vaccination or medication. Immune deficiencies: inherited or acquired . Improper response to foreign (non-pathogenic) antigens: Hypersensitivity and Allergy . Improper response to self : Autoimmune diseases . Rejection of transplanted tissues . Failure to detect cancers . [ Cancer of immune cells.]

34. Immune Deficiencies Inherited: Cellular - when the defective gene is only in T cells; Humoral - when the defective gene is only in B cells; Combined - when the defect is in a gene common to all lymphocytes, e.g., RAGs (recombination activation genes).

35. Acquired - due to: Hemopoietic diseases ; Treatments : chemotherapy, irradiation; Infection : AIDS - caused by the Human Immunodeficiency Virus ( HIV ) which attacks helper T cells. The virus gradually kills more T cells than the body can produce, the immune system fails, and the patient dies from infections that are normally not dangerous. 35

36. Immune Hypersensitivity Hypersensitivity is an improperly strong response . Immediate hypersensitivity: Mediated by antibodies . Types: allergy - up to anaphylactic shock. Induction of antibody-mediated cytotoxicity. Sickness due to accumulation of immune complexes.

37. Delayed hypersensitivity: Mediated by T cells. Hyper-activity of CTLs and macrophages. Contact sensitivity. 37

38. Allergy Allergy is an immune response to harmless antigens. Mechanism: IgE bind FCE receptors on mast cells and basophils , and causes release of granules with inflammatory agents. The “real” role of IgE is probably to fight parasites such as helminths. (In developing countries, people hardly ever suffer from allergies.)

39. Autoimmune diseases Normally, the immune system does not attack the self . This is ensured by elimination of auto-reactive lymphocytes during their development ( negative selection ). However, there is a large group of diseases in which the immune system does attack self-cells: autoimmune diseases . The attack can be either humoral (by auto-antibodies ) or cellular (by auto-reactive T cells ). The attack can be directed either against a very specific tissue, or to a large number of tissues ( systemic autoimmune disease), depending on the self-antigen which is attacked.

40. Autoimmune diseases Specific: Juvenile diabetes (attacks insulin-producing cells) Multiple sclerosis (attacks myelin coating of nerve axons) Myasthenia gravis (attacks nerve-muscle junction) Thyroiditis (attacks the thyroid)

41. Systemic: Immune complexes accumulate in many tissues and cause inflammation and damage. Systemic Lupus Erythematosus (anti-nuclear antibodies): harms kidneys, heart, brain, lungs, skin… Rheumatoid Arthritis (anti-IgG antibodies): joints, hearts, lungs, nervous system… Rheumatic fever : cross-reaction between antibodies to streptococcus and auto-antibodies. 41

42. What could cause the immune system to attack the self? Changes in self-antigens , that make them look like non-self to the immune system, due to: Viral or bacterial infection Irradiation Medication Smoking … Changes in the immune system : Normal auto-antibodies exist; mutations in B cells producing them may create pathogenic auto-antibodies. Problems with control of lymphocyte development and differentiation.

43. Immunological disorders Hypersensitivity mediated disorders Immunodeficiency : 1 and 2 ID Gell and Coomb’s Classification: 4 Types Type 1 : IgE-mediated Type 2 : Cytotoxic antibodies Type 3 : Ag-Ab Immune complexes Type 4 : Delayed-type, cell-mediated hypersensitivity

44. Type I Hypersensitivities: Immediate IgE -Mediated IgE antibody, mast cells/ basophils and its’ mediators (type I) hypersensitivities Characterized by immediate reaction of the sensitized individual Generally within minutes of exposure Tendency to have type I hypersensitivities is inherited Reactions occur in at least 20% to 30% of population Allergen exposure, sensitization and re-exposure Target organ immediate reactions Clinical allergy: atopic diseases, drug allergy, insect allergy and anaphylaxis

45. Type II Hypersensitivity Cytotoxic antibodies: IgG, IgM Mechanisms of cytolysis: Fix complement Clinical spectrums: Autoimmune Hemolytic anemia (AIHA) ABO Miss-matched Stimulatory antibody: Grave’s disease Inhibitory antibody: Myasthenia gravis (anti-Ach Rc)

46. Principle treatments in Type II ABO matching For AIHA, ITP: Steroid, immunosuppressive agents, +/- splenectomy

47. Type III Hypersensitivity Mechanisms : Ag (protein, drugs) + Ab (IgG, IgM) --> Immune complex Immune complex diseases : Serum sickness Autoimmune diseases: prototype-SLE Vasculitis

48. Principle treatments in Type III Serum sickness: Avoidance of heterogeneous protein injection: ERIG antirabies ( equine rabies immunoglobulin ( ERIG ). Autoimmune diseases: SLE Avoidance sun exposure Steroid Immunosupressive agents

49. Type IV Hypersensitivity Delayed-type cell-mediated reaction Mechanism : Antigen (contactants) --> sensitized T-lymphoctyes --> re-exposure --> T cells activation --> cytokines ---> mononuclear cell recruitment --> DTH Clinical disorder : Atopic contact dermatitis Principle treatments in Type IV Avoidance Topical steroid Systemic steroid, if severe

50. Immunodeficiency It is the absence or failure of normal function of one or more elements of the immune system Results in immunodeficiency disease Can be specific or non specific Specific = Abnormalities of B & T cells Non specefic = Abnormalities of non specific components PRIMARY OR SECONDARY 50

51. PRIMARY IMMUNODEFICIENCIES   Primary immunodeficiencies are inherited defects of the immune system These defects may be in the specific or nonspecific immune mechanisms They are classified on the basis of the site of lesion in the developmental or differentiation pathway of the immune system

52. B CELL DEFICIENCY X liked a gammaglobuinemia IgA deficiency IgG subclass deficiency Immunodeficiency with increased Igm Common variable immunodeficiency Transient hypogammaglobulinemia of infancy

53. 1- X-linked a gammaglobulinaemia In X-LA early maturation of B cells fails Affect males Few or no B cells in blood Very small lymph nodes and tonsils No Ig Small amount of Ig G in early age Recurrent pyogenic infection

54. 2- IgA and IgG subclass defeciency IgA deficiency is most common Patients tend to develop immune complex disease About 20% lack IgG2and IgG4 Susceptible to pyogenic infection Result from failure in terminal differentiation of B cells

55. 3- Immunodfeiciency with increased IgM ( HIgM ) Results in patients with IgA and IgG deficiency Production of large amount of IgM >200mg/dl of polyclonal IgM Susceptible to pyogenic infection Treatment by iv gamma globulin Formation of IgM to neutrophils, platelets and other blood components Due to inability of B cells to isotype switching

56. 4- Common Variable Immunodeficiency (CVID) There are defect in T cell signaling to B cells Acquired a gammaglobulinemia in the 2 nd or 3 rd decade of life May follow viral infection Pyogenic infection 80% of patients have B cells that are not functioning B cells are not defective. They fail to receive signaling from T lymphocytes Unknown

57. 5- Hypogamaglobulinaemia of infancy Due to delay in in IgG synthesis approximately up to 36 months In normal infants synthesis begins at 3 months Normal B lymphocytes Probably lack help of T lymphocytes

58. DISORDERS of T CELLS DiGeorge's syndrome: It the most understood T-cell immunodeficienc Also known as congenital thymic aplasia/hypoplasia Associated with hypoparathyroidism , congenital heart disease, fish shaped mouth. Defects results from abnormal development of fetus during 6th-10th week of gestation when parathyroid, thymus, lips, ears and aortic arch are being formed

59. T cell deficiencies with variable degrees of B cell deficiency 1- Ataxia-telangiectasia: Associated with a lack of coordination of movement ( ataxis ) and dilation of small blood vessels of the facial area ( telangiectasis ). T-cells and their functions are reduced to various degrees. B cell numbers and IgM concentrations are normal to low. IgG is often reduced IgA is considerably reduced (in 70% of the cases).

60. 2- Wiskott -Aldrich syndrome : Associated with normal T cell numbers with reduced functions , which get progressively worse. IgM concentrations are reduced but IgG levels are normal Both IgA and IgE levels are elevated. Boys with this syndrome develop severe eczema. They respond poorly to polysaccharide antigens and are prone to pyogenic infection.

61. Defects of the phagocytic system Defects of phagocytic cells (numbers and/or functions) can lead to increased susceptibility to a variety of infections. 1- Cyclic neutropenia: It is marked by low numbers of circulating neutrophil approximately every three weeks. The neutropenia lasts about a week during which the patients are susceptible to infection. The defect appears to be due to poor regulation of neutrophil production.

62. 2- Chronic granulomatous disease (CGD): CGD is characterized by marked lymphadenopathy, hepato - splenomegaly and chronic draining lymph nodes. In majority of patients with CGD, the deficiency is due to a defect in NADPH oxidase that participate in phagocytic respiratory burst.

63. 3- Leukocyte Adhesion Deficiency: Leukocytes lack the complement receptor CR3 due to a defect in CD11 or CD18 peptides and consequently they cannot respond to C3b opsonin . Alternatively there may a defect in integrin molecules, LFA-1 or mac-1 arising from defective CD11a or CD11b peptides, respectively. These molecules are involved in diapedesis and hence defective neutrophils cannot respond effectively to chemotactic signals. 

64. 4- Chediak-Higashi syndrome: This syndrome is marked by reduced (slower rate) intracellular killing and chemotactic movement accompanied by inability of phagosome and lysosome fusion and proteinase deficiency. Respiratory burst is normal. Associated with NK cell defect, platelet and neurological disorders

65. Diagnosis Is based on enumeration of T and B cells and immunoglobulin measurement. Severe combined immunodeficiency can be treated with bone marrow transplant

66. SECONDARY IMMUBODEFICIENCY

67. Secondary: These disorders generally develop later in life and often result from use of certain drugs or from another disorder, such as diabetes or human immunodeficiency virus (HIV) infection. They are more common than primary immunodeficiency disorders. Some immunodeficiency disorders shorten life span. Others persist throughout life but do not affect life span, and a few resolve with or without treatment. 67

68. Secondary immunodeficiency disorders These disorders can result from Prolonged (chronic) and/or serious disorders such as diabetes or cancer Drugs Rarely, radiation therapy Immunodeficiency disorders may result from almost any prolonged serious disorder. For example, diabetes can result in an immunodeficiency disorder because white blood cells do not function well when the blood sugar level is high. Human immunodeficiency virus (HIV) infection results in acquired immunodeficiency syndrome (AIDS), the most common severe acquired immunodeficiency disorder. 68

69. Symptoms Respiratory infections (such as sinus and lung infections Infections of the mouth, eyes, and digestive tract chronic gum disease (gingivitis) and frequent ear and skin infections Many people have fevers and chills and lose their appetite and/or weight. Abdominal pain may develop, possibly because the liver or spleen is enlarged. 69

70. Many types of cancer can cause an immunodeficiency disorder. For example, any cancer that affects the bone marrow (such as leukemia and lymphoma) can prevent the bone marrow from producing normal white blood cells (B cells and T cells), which are part of the immune system. 70

71. INTRODUCTION TO HIV/AIDS 71

72. 72 Content Overview What is HIV? What is AIDS? The HIV pandemic HIV transmission Window period Stages of HIV infection

73. 73 What is HIV? H uman: Infecting human beings I mmunodeficiency: Decrease or weakness in the body’s ability to fight off infections and illnesses V irus: A pathogen having the ability to replicate only inside a living cell

74. Basic concepts of HIV/AIDS What is HIV/AIDS? HIV: Human Immunodeficiency Virus AIDS: Acquired Immuno Deficiency Syndrome Acquired: acquired, not inherited Immuno : weakness the immune system Deficiency: deficiency of certain WBCs in the immune system Syndrome: a group of symptoms or illnesses as a result of HIV infection 74

75. Historical Back Ground 1981: AIDS was first recognized in USA among Homosexual males PCP was seen among 5 homosexuals Kaposi’s sarcoma was diagnosed in 26 homosexuals 1983: HIV virus was isolated from a patient with lymph -adenopathy 1984: HIV virus was clearly demonstrated to be the causative agent for AIDS There are approximately 36.7 million people currently living with HIV in 2015. 10 millions of people have died of AIDS-related causes since the beginning of the epidemic. 75

76. The HIV epidemic in Ethiopia Prevalence refers to the total number of cases of a particular disease or health condition existing in a population at a certain point in time, or during a given period. Incidence refers only to the numbers of new cases of a disease or condition that are identified in a given period. 76

77. In Ethiopia, there were an estimated 1.2 million PLHIV in 2010. Thus, the prevalence of HIV infection in Ethiopia in 2010 was estimated to be 2.4% of the general population (2.9% of all females and 1.9% of all males). Women and children are particularly affected by HIV/aids; In 2010, close to 60% of the PLHIV in the country were females (totaling around 700,000 women) and about 80,000 were children. 77

78. There is a marked variation in HIV infection between regions in Ethiopia 78

79. 79 Types of HIV Virus There are two species of HIV, known as HIV-1 and HIV-2 HIV 1 Most common in sub-Saharan Africa and throughout the world Comprises several subtypes with different geographic distributions. Groups M, N, and O There are d/t groups of HIV-1: Pandemic dominated by Group M (major), which is responsible for most of the infections in the world Group O (outlier), a relatively rare viral form found originally in Cameroon, Gabon, and France

80. Conti….. The M group comprises eight subtypes, designated A, B, C, D, F, G, H, and J Subtype C is the most common worldwide In Africa, >75% of strains are subtypes A, C & D Subtype B is predominant in USA, Canada, South America, western Europe, and Australia. In Asia, subtypes C and B are predominant 80

81. Conti….. HIV 2 Found primarily in west Africa: Mozambique & Angola, parts of Europe and India Less easily transmittable Develops more slowly MTCT is relatively rare Most often found in West Central Africa 81

82. HIV 1 & HIV 2 Transmitted through the same route Associated with similar opportunistic infections HIV attacks white blood cells, attaching itself to cells with the help of a specific surface protein called CD4 CD4 is present on T helper lymphocytes and macrophages and the virus mainly infects these cells 82

83. Morphology of the Virus 83

84. HIV is Spherical shaped virus. The most important parts of the virus are:- Its viral envelop has many small spikes which consists of two important glycopropteins gp41 and gp120 Which play an important role when the virus attaches to its host cells The viral capsid( core ) which contains two single stranded viral RNA and an important enzyme for the virus called reverse transcriptase enzyme 84

85. The reverse transcriptase enzyme plays an important step in the life cycle of the virus. It converts the single stranded viral RNA into double stranded DNA ( this process is called reverse transcription) 85

86. Characteristics of HIV HIV infect cells that express CD4 receptor molecules Successful entry of the virus to a target cell also requires cellular co-receptors A fusion co-receptor is designated CXCR5 for T-cell tropic stain and CCR4 for monocyte -macrophage tropic strains The receptor and co-receptors of CD4 cells interact with HIV’s gp-120 and gp-41 proteins during entry into a cell 86

87. Life Cycle of HIV: Replication 1) Attachment /binding and fusion of the virus to the host cells The receptor and co-receptors of CD4 cells interact with HIV’s gp-120 and gp-41 proteins during entry into a cell 2) Uncoatting of the viral capsid and release of Viral RNA into the cytoplasm of the host cell( Fusion Viral envelope fuses with cell membrane, releasing contents into the cell. 3) Reverse transcription: Viral RNA is concerted in to Double stranded DNA by reverse transcriptase enzyme 87

88. Retroviruses, such as HIV, have RNA that is transcribed into DNA by the viral enzyme reverse transcriptase upon entry into the cell. (The ability of retroviruses to copy RNA into DNA earned them their name because this process is the reverse of the usual transfer of genetic information, from DNA to RNA.) The DNA form of the retrovirus genome is then integrated into the cellular DNA and is referred to as the provirus. The viral genome is replicated every time the host cell replicates its DNA and is thus passed on to daughter cells. 4) Translocation : viral DNA is Imported to cell nucleus

89. Conti….. 5) I ntegration of proviral DNA to host-cell DNA ( Viral DNA is inserted into host cell chromosome by unique enzyme integrase(P32) . Integrated viral DNA may remain latent for years and is called a provirus . 6) Cellular activation causes transcription (copying) of HIV DNA back to RNA Some RNA translated to HIV proteins Other RNA moved to cell membrane Replication: Viral DNA is transcribed and RNA is translated, making viral proteins. Viral genome is replicated. 89

90. Conti… 7) Viral Assembly :HIV assembled under cell membrane and buddes from cell ( New viruses are made). 8) Maturation : viral Proteases enzymes cleave longer proteins in to important viral proteins and help to convert immature viral particle into and infectious HIV ( New viruses bud through the cell membrane). 90

91. HIV Life Cycle: Latent versus Active Infection

92. HIV Life Cycle: Latent versus Active Infection in Macrophages

93. Antiviral agents can potentially target any of these steps. 93

94. AIDS and HIV ‘THE NATURAL HISTORY’ HIV POSITIVE PERSON AIDS PATIENT NORMAL PERSON WINDOW PERIOD (3 MONTHS) PROMISCOUS SEX

95. Progression of HIV is different in different individuals Rapid progressors: After the initial infection patients progress fast and develop OIs and die within 2-3 years. Account for 15 % of all patients Normal Progressors: After the initial primary infection patients remain health for 6-8 years before they start having overt clinical manifestations: account for 80 % of all patients Patients who remain alive for 10-15 years after initial infection. In most the diseases might have progressed and there may be evidences of immunodeficiency. 95

96. Conti….. Long term survivors:. Patients who remain alive for 10-15 years after initial infection. In most the diseases might have progressed and there may be evidences of immunodeficiency 96

97. What affects disease progression in HIV Infected individuals Viral set point: The level of steady-state viremia (set-point) at six months to one year after infection, Has an important prognostic implication for progression of HIV disease Those with a high viral set-point have faster progression to AIDS, if not treated Immune response High CD8 slow progression Low CD8 rapid decline 97

98. Conti….. Viral type; HIV 2 slow course Concomitant conditions Malnutrition hastens the progression of HIV Chronic infectious conditions e.g. Tuberculosis 98

99. Window period The period after infection but before the test becomes positive. Amount of time for your body to start making HIV antibodies . The window period can be from 9 days to 3-6 months , depending on the person's body and on the HIV-test that's used. The immune system usually takes 3 to 8 weeks to make antibodies against HIV, but tests differ in how early they are able to detect antibodies. 99

100. Window period A few people will have a longer window period, so if you get a negative antibody test result in the first 3 months after possible exposure, you should get a repeat test after 3 months. 97% of people will develop antibodies in the first 3 months after they are infected. In very rare cases, it can take up to 6 months to develop antibodies to HIV. Antibody tests cannot accurately identify infection during this time Immediately contagious 100

101. Diagnosis and Laboratory monitoring of HIV 1. Serologic Tests : a. HIV antibody tests :-detect antibodies formed by the immune system against HIV i . ELISA : used to be standard screening test for HIV Tests for a number of antibody proteins in combination A very sensitive test ( 99.5 % ), but not very specific A positive result needs to be confirmed by Western blot for confirmation The test need skilled personnel , takes several hours 101

102. Conti….. ii. Western blot: is an excellent confirmatory test . It has high specificity but relatively poor sensitivity It should not be used for screening purpose iii. Rapid HIV antibody testes Advantages: Rapid tests have reasonably good sensitivity and specificity ( >99 % ) Easy logistically , does not need continuous water or electric supply Can be done by less skilled personnel and the interpretation of results is easy Test result can be made available in < 30 minutes 102

103. b. HIV antigen assays ( Tests ) i.P24 antigen capture assay: this test detects p24 viral protein in the blood of HIV infected individuals. This viral protein can be detected during early infection, before sero conversion. Thus this test is used to detect blood donors during the Window period 103

104. Conti….. 2. DNA –PCR : Viral replication Is an extremely sensitive test -can detect 1-10 copies of HIV proviral DNA per ml of blood. It uses PCR technology to amplify proviral DNA This test is costly and needs sophisticated instruments and highly skilled professional It is highly sensitive and the chance of false positivity is high. Hence it should not be used for making initial diagnosis of HIV infection. 104

105. Conti….. It is often used i . To make early diagnosis of HIV in HIV exposed infants as serology tests are unable to diagnose HIV till the infant is 18 months old. ii. To diagnose or confirm virologic failure in patients who are not responding to ART iii. When there is indeterminate serology 105

106. Conti….. 3. CD4 T cell count : as CD4 cells play a crucial role in the body defense mechanism. measuring the amount of CD4 cells is an important indicator of the level of immune suppression that a patient infected with HIV. In patients with HIV CD4 count drops by an average of 50 -100 cells per year Tells you the level of immune damage inflicted by HIV. 106

107. Conti….. It should never used to make diagnosis of HIV CD4 count may be variable depending on circumstances Diurnal variation; High evening low at midnight Inter current infection, use of steroids and stress could affect CD4 count Following the trend in CD4 count is us full in clinical decision making Percentage of CD4 count is useful in children below 6 years 107

108. Conti….. Importance’s of CD4 count To decide eligibility of a patient for ART To follow the progress of a patient on ART To diagnose immunologic failure in patients who are not responding well to ART 108

109. What are opportunistic infections? An opportunistic infection is an infection caused by harmful infectious agents, or pathogens (bacteria, viruses, fungi, parasites or protozoa), That usually do not cause disease in a healthy person, i.e. one with an immune system whose function is not impaired. Opportunistic infections observed in PLHIV include a wide range of diseases, from minor ailments like chronic skin itching to severe diseases such as tuberculosis (TB). 109

110. Conti….. When the CD4 count has decreased below 450 cells/mm³ , a person living with HIV will start to acquire some mild or moderate opportunistic infections. When the CD4 count has decreased below 200 cells/mm³ , a person living with HIV is highly likely to acquire severe opportunistic infections. CD4 cells reside primarily (although not exclusively) in the blood, where they are most likely to encounter 110

111. WHO HIV clinical stages Staging means categorizing the patient clinically into one of the four WHO HIV stages. It is useful to know these stages because it enables you clinically to identify patients with mild and severe diseases associated with HIV. 111

112. WHO Clinical Staging of HIV Disease in Adults and Adolescents CLINICAL STAGE 1 Asymptomatic Persistent generalized lymphadenopathy(PGL) (PGL-is defined as the presence of lymph node > 1cm , In two extra inguinal sites and persisting for more than three months)

113. WHO Clinical Staging of HIV Disease in Adults and Adolescents CLINICAL STAGE 2 Moderate unexplained weight loss (<10% of presumed or measured body weight) Recurrent respiratory tract infections: sinusitis, tonsillitis, otitis media and pharyngitis ) Herpes zoster Angular cheilitis Recurrent oral ulceration Papular pruritic eruptions Seborrhoeic dermatitis Fungal nail infections

114. Varicella Zoster Virus Disease: Epidemiology Reactivation of VZV that had been latent in dorsal root ganglia since original infection with VZV (chickenpox) Herpes zoster occurs in 3-5% of adults and more prevalent in immunocompromised and elderly Incidence 15-25 times greater in HIV-infected than in general population Can occur at any CD4 count Advanced immunosuppression may change manifestations but does not substantially change incidence

115. Varicella Zoster Virus Disease: Clinical Manifestations Herpes zoster (shingles): prodrome of pain in affected dermatome, then characteristic skin lesions in same dermatome Extensive skin involvement or visceral involvement are rare Progressive outer retinal necrosis may be seen, usually with CD4 count <50 cells/µL Rapid progression and vision loss Acute retinal necrosis due to peripheral necrotizing retinitis may occur at any CD4 count (more often at higher CD4)

116. Varicella Zoster Virus Disease: Clinical Manifestations Chickenpox: primary VZV infection, uncommon in adults and adolescents Respiratory prodrome, then vesiculopapular lesions (face and trunk > extremities) In advanced immunosuppression, may persist for weeks Reports of transverse myelitis, encephalitis, vasculitic stroke

117. Varicella Zoster Virus Disease: Diagnosis Clinical diagnosis based on appearance of lesions Viral culture or antigen detection from swabs from fresh lesion or tissue biopsy

118. BACTERIAL SKIN INFECTION (PRURITIC PAPURIC ERUPTIONS) BACTERIAL SKIN INFECTION (PRURITIC ECZEMATOUS ERUPTIONS

119. Seborrheic Dermatitis

120. SEBORRHEIC DERMATITIS

121. WHO Clinical Staging of HIV Disease in Adults and Adolescents CLINICAL STAGE III Unexplained severe weight loss (>10% of presumed or measured body weight) Unexplained chronic diarrhea for longer than one month Unexplained persistent fever (above 37.6°C intermittent or constant, for longer than one month) Persistent oral candidiasis Oral hairy leukoplakia

122. CLINICAL STAGE 3 cont ; Pulmonary tuberculosis (current) Severe bacterial infections (such as pneumonia, empyema, pyomyositis, bone or joint infection, meningitis or bacteremia) Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis Unexplained anemia (<8 g/dl), neutropenia (<0.5 × 109 per liter) or chronic Thrombocytopaenia (<50 × 109 per litre)

123. Mucocutaneous Candidiasis: Epidemiology Oropharyngeal and esophageal candidiasis are common Most common in patients with CD4 count <200 cells/µL Prevalence lower in patients on ART Vulvovaginal candidiasis Occurs in non-HIV-infected women; does not indicate immunosuppression In advanced immunosuppression, may be more severe or recur more frequently Usually caused by Candida albicans ; other species (especially C glabrata ) seen in advanced immunosuppression, refractory cases

124. Mucocutaneous Candidiasis: Clinical Manifestations Oropharyngeal (thrush): Pseudomembranous: painless, creamy white plaques on buccal or oropharyngeal mucosa or tongue; can be scraped off easily Erythematous: patches on anterior or posterior upper palate or tongue Angular cheilosis Esophageal: retrosternal burning pain or discomfort, odynophagia, fever; on endoscopy, whitish plaques with or without mucosal ulceration Vulvovaginal : creamy discharge, mucosal burning and itching

125. Mucocutaneous Candidiasis: Diagnosis Oropharyngeal : Usually clinical diagnosis KOH preparation, culture Esophageal: Clinical, with trial of therapy Endoscopy with histopathology and culture Vulvovaginal : Clinical diagnosis, KOH preparation

126. WHO Clinical Staging of HIV Disease in Adults and Adolescents CLINICAL STAGE IV HIV wasting syndrome Pneumocystis pneumonia Recurrent severe bacterial pneumonia Chronic herpes simplex infection ( orolabial , genital or anorectal of more than one month’s duration or visceral at any site) Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs) Extrapulmonary tuberculosis

127. CLINICAL STAGE IV cont ; Kaposi’s sarcoma Cytomegalovirus infection (retinitis or infection of other organs) Central nervous system toxoplasmosis HIV encephalopathy Extrapulmonary cryptococcosis including meningitis Disseminated non- tuberculous mycobacterial infection

128. Progressive multifocal leukoencephalopathy Chronic cryptosporidiosis (with diarrhoed ) Chronic isosporiasis Disseminated mycosis ( coccidiomycosis or histoplasmosis ) Recurrent non- typhoidal Salmonella bacteraemia Lymphoma (cerebral or B-cell non-Hodgkin) or other solid HIV-associated tumours 129

129. CLINICAL STAGE IV cont ; Invasive cervical carcinoma Atypical disseminated leishmaniasis Symptomatic HIV-associated nephropathy or symptomatic HIV-associated cardiomyopathy

130. Pneumocystis jiroveci Pneumonia: Epidemiology Caused by P jiroveci (formerly P carinii ) PCP may result from reactivation or new exposure In immunosuppressed patients, possible airborne spread Risk factors: CD4 count <200 cells/µL CD4% <15% Oral thrush Recurrent bacterial pneumonia Unintentional weight loss High HIV RNA

131. PCP: Clinical Manifestations Progressive exertional dyspnea, fever, nonproductive cough, chest discomfort Subacute onset, worsens over days-weeks (fulminant pneumonia is uncommon) Chest exam may be normal, or diffuse dry rales , tachypnea, tachycardia (especially with exertion) Extrapulmonary disease seen rarely; occurs in any organ, associated with aerosolized pentamidine prophylaxis

132. HPV (MUCOSAL VIRAL WARTS)

133. HPV II GENITALIA

134. COMMON SITES FOR KAPOSIS SARCOMA

135. COMMON SITES FOR KAPOSIS SARCOMA

136. EXTENSIVE CUTENOUS KAPOSIS SARCOMA

137. EXTENSIVE CUTENOUS KAPOSIS SARCOMA

138. Cryptococcosis: Epidemiology Caused by Cryptococcus neoformans Most cases seen in patients with CD4 count <50 cells/µL 5-8% prevalence in HIV-infected patients in developed countries before widespread use of effective ART Incidence much lower with use of ART

139. Cryptococcosis: Clinical Manifestations Subacute meningitis or meningoencephalitis (most common presentation) Fever, malaise, headache Neck stiffness, photophobia, or other classic meningeal signs and symptoms in 25-35% of cases Lethargy, altered mental status, personality changes (rarely) Acute illness with nuchal rigidity, seizures, focal neurologic signs observed in developing countries

140. Cryptococcosis: Clinical Manifestations Disseminated disease is common: often pulmonary infection with or without meningeal involvement Cough, dyspnea, abnormal chest X ray Skin lesions Papules, nodules, ulcers, infiltrated plaques seen in disseminated disease

141. Conti….. Angular chelitis : Oral thrush 142

142. WHO Recommendation A. Establish the mechanisms for collaboration 1.Set up a coordinating body for TB/ HIV activities effective at all levels 2.Conduct surveillance of HIV prevalence among tuberculosis patients 3.Carry out joint TB/HIV planning 4.Conduct monitoring and evaluation B.DecreasetheburdenoftuberculosisinpeoplelivingwithHIV/AIDS 1.Establishintensifiedtuberculosiscase-finding 2.Introduceionizedpreventivetherapy.INH300mg/dfor6-9months. 3.Ensuretuberculosisinfectioncontrolinhealthcareandcongregatesettings 143

143. Conti….. C. Decrease the burden of HIV in tuberculosis patients 1.ProvideHIVtestingandcounseling 2.IntroduceHIVpreventionmethods 3.Introduceco-trimoxazolepreventivetherapy 4.EnsureHIV/ AIDScareandsupport 5.Introduceantiretroviraltherapy 144

144. Overview HIV Post-Exposure Prophylaxis (PEP) Hepatitis B and C post-exposure protocols

145. Post-Exposure Prophylaxis (PEP) PEP is the use of therapeutic agents to prevent infection following exposure to a pathogen. In the case of HIV, Post-exposure prophylaxis (PEP) is short-term antiretroviral treatment to reduce the likelihood of HIV infection after potential exposure. The types of exposures include percutaneous (needle stick injury), splash, bite, suspected sexual assaults. For health-care workers, PEP commonly is considered for exposures to HIV and Hepatitis B. 146

146. The least expensive way to deal with a disease is via prevention. The implementation of standard Precautions with appropriate training and monitoring is the number one priority. Although standard Precautions will decrease the need for PEP there are “accidents” and unanticipated occupational exposure. PEP will be made available free of charge for accidental occupational exposures for health workers and emergency personnel as well as for rape victims. 147

147. Risk of viral transmission with sharp injury from infected source Source Risk (%) Source Risk (%) HBsAg+ 30 HCV 1.8 HIV 0.3 0.3 148 The risk of transmission of HIV is much less than that of Hepatitis B by a factor of 100. These transmission rates apply to occupation risk due to sharp injury.

148. Cotrimoxazole treats The most commonly used prophylactic drug for HIV/AIDS is cotrimoxazole. A wide-spectrum antibiotic that targets the pathogens causing the most common opportunistic infections. Pneumocysitiscarni/ jerovecipneumonia (PCP) Streptococcus pneumonia Isosporabelli (causes of entritis) Toxopasmosis Malaria (plasmodium falciparum) Shigellosis 149

149. Criteria for starting cotrimoxazole prophylaxis by adult All HIV-positive people at WHO clinical stages 2, 3, 4, Or with a CD4 count less than 350 cells/mm³, should start cotrimoxazoleprophylaxis. The drug regimen for cotrimoxazoleprophylaxis is two 480 mg tablets, or one 960 mg tablet daily. 150

150. Duration of cotrimoxazole prophylaxis for adult PLHIV If a person living with HIV has no access to HIV treatment, cotrimoxazoleprophylaxis should be taken for the rest of the patient’s life . If the patient has access to antiretroviral therapy (ART) for HIV, cotrimoxazoleprophylaxis should be stopped when the CD4 count has increased to 350 cells/mm³ and remains above that level for at least six months. 151

151. Key Elements of Post-Exposure Prophylaxis (PEP) Programs Medical knowledge Indications Regimens Follow-up Programmatic readiness Awareness of need Timely availability of medical evaluation and PEP agents Availability of follow-up Confidentiality and documentation

152. Key Elements Assess Risk Manage Exposure Determine HIV Status of source, when possible Dispense PEP if indicated Educate and Counsel Exposed Patient Documentation

153. Assess Risk Percutaneous injury Contact of mucous membrane Contact non-intact skin Assess Risk: Blood or Body Fluid Fluids with Risk: Blood or visibly bloody fluid Semen Vaginal secretions Cerebrospinal fluid Synovial fluid Pleural fluid Pericardial fluid Amniotic fluid

154. Community Needlestick Injuries Consider: HIV prevalence in the community or facility Surrounding prevalence of injection drug use Do not test discarded needles for HIV False negatives Risk Non-risky Fluids* Saliva, sputum or nasal secretions Tears Sweat Urine Stool Emesis *Unless there is visible blood

155. 156

156. PEP of Non-Occupational Exposures PEP recommended if source HIV+, high-risk, unknown (e.g. sexual assault) PEP NOT recommended Unprotected vaginal/anal intercourse (receptive or insertive) Unprotected receptive penile-oral contact with ejaculation Oral-vaginal contact with blood exposure Needle-sharing Injury with blood exposure needlestick, bite, accident Consider PEP when: Blood exposure to biter and/or bitten person (e.g. source has bleeding gums or lesions) Blood exposure unknown Kissing, or oral-oral contact & no mucosal damage Bites without blood Needles/sharps exposure not in contact with HIV + or at-risk person Mutual masturbation – intact skin Oral-anal contact Receptive penile-oral contact without ejaculation Insertive penile-oral contact Oral-vaginal – no blood exposure

157. Exposure Management Wash immediately w/ soap and water Flush mucous membranes with water No evidence that use of antiseptics or expressing fluid reduces potential transmission Antiseptics not indicated; caustic agents (bleach) not recommended “Milking the wound” may increase risk increases local inflammation

158. 4. PEP Recommendations PEP ideally within 2 hrs, no later than 36 hrs from exposure HAART (3 antiretroviral drugs) x 4 weeks Baseline HIV serology of exposed person within 72 hours of initiating PEP HIV specialist follow-up within 72 hours PEP Recommendations Beyond 36 Hours? “Decisions regarding initiation of nPEP beyond 36 hours post exposure should be made by the clinician in conjunction with the patient with the realization of diminished potential for success when timing of initiation is prolonged”1 Consider likelihood of HIV transmission

159. Preferred PEP Regimen Zidovudine (AZT) 300 mg po bid Lamivudine (3TC) 150 mg po bid PLUS Tenofovir 300 mg po daily with food OR Zidovudine 300 mg po bid PLUS Tenofovir 300 mg PO qd Emtricitabine 200mg po qd Combivir 1 po bid Truvada 1 po qd

160. CDC: Basic HIV PEP Regimen zidovudine (ZDV) + lamivudine (3TC) or emtricitabine (FTC) ZDV 300 mg BID; 3TC 300 QD or 150 BID; FTC 200 QD tenofovir (TNF) + lamivudine (3TC) or emtricitabine (FTC) TNF 300 mg QD// 3TC 300 QD or 150 BID; FTC 200 QD lopinavir/ritonavir (LPV/RTV) (or efavirenz LPV/RTV: 400/100 mg = 2 tablets twice daily with food Medication Side Effects Nausea Vomiting Fatigue Headache Loss of appetite Diarrhea

161. Antiretroviral therapy Learning objectives By the end of this session you expected to: Demonstrate how to prepare a patient for ART initiation Describe the requirements for ART initiation Discuss when and what to start first line ARV regimen Describe what to expect in the first few months after ARV initiation Describe common drug interactions that may occur in patients taking ARV Describe how to monitor for treatment response, drug toxicity and Rx failure 162

162. Introduction ART What is ART? A-anti R-retroviral T-Therapy ART is the treatment of HIV infected individual with anti-retroviral drug. What is HAART? H-Highly A-Active A-anti R-retroviral T- treatment 163

163. Goals of ART The goal of ART is to reduce the number of virus in the blood and increase the number of CD4 as much as possible. NB: The virus can never be eradicated completely from the body; hence the person should take the drugs forever, even if the symptoms have disappeared. NB: Since the virus cannot be eradicated safer sex should be practiced. 164

164. The benefits of ART The benefits of ART can be divided into three — benefits to PLHIV, benefits to the health service, benefits to the community at large. 165

165. Conti….. Benefits of ART to the patient: Prolongs life and improves quality of life. Decreased stigma surrounding HIV infection Households can stay intact, because patients survive for longer. Businesses and jobs can stay intact for the same reason. Reduces mother-to-child transmission of HIV. Less money is spent on treating opportunistic infections and providing palliative care (end-of-life care). 166

166. Conti….. Benefits of ART to the health service: Increased number of people who accept HIV testing and counselling . Increased motivation of health workers, since they feel they can do more for PLHIV. Benefits of ART to the community: Decreased number of orphans. Increased awareness of HIV in the community, since more people accept HIV counselling and testing. 167

167. Antiretroviral drugs (ARVs) and antiretroviral therapy (ART) Drugs that are used to treat HIV infection are called antiretroviral drugs, which can be shortened to ARVs. Antiretroviral therapy (HIV treatment), also known as ART, is a treatment that uses ARV drugs 168

168. The two main goals of ART are: 1 . To reduce the number of viruses in the patient’s blood to a very low level 2. To increase the number of CD4 lymphocytes in the patient as much as possible, to increase the body’s immunity to infection, including immunity against HIV. 169

169. Preparing patients for ART Before people start ART, it is important to have a detailed discussion with them about their willingness and readiness to initiate ART. The following issues should be addressed during the preparation: The likely benefits Possible adverse effects Provide information regarding lifelong treatment The required follow-up and monitoring visits. Detailed examination and treatment of OIs Proper adherence counseling and support -Education on safer sex practice and screening of family members 170

170. Requirements for initiation of ART 1. HIV positive test result with written documentation 2. Ensure that all adherence barriers are addressed 3. Start only patients with medical eligibility for ART 4. Any opportunistic infection has been screened and addressed according to the standard guidelines 5. Ensure readiness of patient for ARV therapy 171

171. Summary of recommendations on when to start ART in adults, adolescents, pregnant and breastfeeding women and children. All Adults and adolescents a. HIV infection with CD4 count ≤500 cells/mm should be started on HAART irrespective of WHO clinical stage. b. HIV infection and WHO clinical stage 3 and 4 should be started on HAART irrespective of CD4 cell count. c. HIV infection and Active TB disease should be started on HAART irrespective of CD4 cell count d. All HIV positive pregnant and breast feeding women irrespective of CD4 count e. Provide ART to all HIV infected partners of sero discordant couple regardless of CD4 cell count (to reduce the risk of HIV transmission to the negative partner) 172

172. Groups of ARV drugs There are three big groups of ARV drugs available in Ethiopia: 1 The NRTI drugs: this stands for ‘Nucleoside and Nucleotide Reverse Transcriptase Inhibitors’ (divided into NsRTIsand NtRTIs). 2 The NNRTI drugs: this stands for ‘Non-Nucleoside Reverse Transcriptase Inhibitors’. 3 The PI drugs: this stands for ‘Protease Inhibitors’. 173

173. Nucleoside reverse transcriptase inhibitors ( NsRTI ) Stavudine(d4T) Lamivudine(3TC) Zidovudine(AZT or ZDV) Didanosine(ddI) Abacavir(ABC) 174

174. Nucleotide reverse transcriptase inhibitors ( NtRTI ) Tenofovirdisoproxilfumarate (TDF) Non-nucleoside reverse transcriptase inhibitors (NNRTI) Nevirapine (NVP) Efavirenz (EFV) Protease inhibitors (PI) Lopinavir (LPV) Ritonavir (RTV) Atazanavir (ATV) 175

175. How are antiretroviral drugs combined? A prescribed or recommended collection of medications intended to treat a disease is called a treatment regimen (or simply a regimen). The regimens used in ART can be first line, second line. 176

176. Common first-line drug regimens for ART What ART regimen to start with (first-line ART)? Using simplified, less toxic and more convenient regimens as fixed-dose combinations is recommended for first-line ART. Once-daily regimens comprising NRTI backbone (TDF + 3TC) and one NNRTI (EFV) are maintained as the preferred choices in adults, adolescents and children AZT-3TC-NVP AZT-3TC-EFV d4T-3TC-NVP d4T-3TC-EFV TDF-3TC-EFV TDF-3TC-NVP 177

177. Classes and Dosages of anti-RVD for Adults and Adolescents and children currently used in Ethiopia Drug class/ drug Dose Nucleoside RTIs Abacavir (ABC) 300 mg twice daily Lamivudine (3TC) 150 mg twice daily or 300 mg once daily Zidovudine (ZDV) 300 mg twice daily. Nucleotide RTI Tenofovir (TDF) 300 mg once daily Non-nucleoside RTIs Efavirenz (EFV) 600 mg once daily Nevirapine (NVP) 200 mg daily for the first 14 days, then 200 mg twice daily Protease inhibitors Lopinavir/ ritonavir (LPV/r) 400 mg/ 100 mg twice daily Atazanavir /ritonavir(ATV/r) 300mg/100 once daily 178

178. WHY DO WE HAVE TO USE THE COMBINATION OF 3 ARV DRUGS? It takes three drugs to have sustained viral suppression (low level of virus in the body). HIV makes new copies of itself very rapidly. Everyday billions of new copies of HIV are made and many infected cells die. Giving a single drug might suppress viral replication for a short period of time but resistance to the drug develops soon. The same holds true to two drugs regimen and therefore giving two drugs alone for treatment is strongly discouraged. Whenever ART is given, it is administered as a minimum of three drugs combination referred as HAART. 179

179. Antiretroviral drugs from different drug groups attack the virus in different ways. Hitting two targets increases the chance of stopping HIV and protecting new cells from infection. Combinations of anti-HIV drugs may overcome or delay resistance. Resistance is the ability of HIV to change its structure in ways that make ARV drugs less effective. HIV has to make only a single, small change to resist the effects of some drugs. 180

180. Second-line regimens Many patients on ART will eventually develop failure of therapy, which means the first-line regimen will not be effective anymore. This is often because the drugs were not taken correctly, and this allowed HIV to become resistant to them. In that case, the doctor may decide to switch to a second line regimen, which is more expensive. Usually, the second-line regimen will consist of two NRTIs and one PI drug in combination. 181

181. HIV/AIDS Prevention & Control Strategies Risk reduction Vulnerability reduction Ensure the safety of the blood supply Provide HIV-related information and education Condom Promotion and Distribution Management STIs Care, Support and treatment 182

182. 183 8/18/2020 By Emiru Ayalew (Lecturer ,BDU ) MSC IN ADULT HEALTH