1. The National Shared Vision To See a HIV Free New Generation By 2020 !!

2. Welcome To The National PMTCT Training of Trainers/Facilitators Course FHAPCO/MOH

3. PMTCT_Module1 Introduction to HIV/AIDS and PMTCT Ministry of Health/HAPCO

4. Objectives By the end of this module you will be able to:  Explain the basics of HIV/AIDS  Describe global and national magnitude and impact of HIV  Describe the clinical stages of HIV  Describe the basics of PMTCT  Describe the different calss of ARVs  Introduction to ART and prophylaxis  Common side effects of ARV drugs, adherence and palliative care principles

5. Reading exercise

6. Section 1- Basics of HIV/AIDS What is HIV,? What types exist? What does it stand for?

7. The HIV Epidemic Unfolds Sudden outbreak in USA of opportunistic infections and cancers in homosexual men in 1981  Pneumocystis carinii pneumonia (PCP), Kaposi’s sarcoma, and non-Hodkins lymphoma HIV isolated in 1984 - Luc Montanier (Pasteur Institute, Paris) and Robert Gallo (NIH, Bethesda, USA) HIV diagnostic tests developed in 1985

8. First antiretroviral drug, zidovudine, developed in 1986 Exploding pandemic  Has infected more than 50 million people around the world  Has killed over 22 million people

9. Classification of HIV HIV type (distinguished genetically)  HIV-1 - worldwide pandemic (current ~ 33 M people)  HIV-2 - isolated in West Africa; causes AIDS much more slowly than HIV-1 but otherwise clinically similar

12. Section 1 HIV can be transmitted  Sexual ( anal, vaginal, oral) with infected partner  Blood transfusion  Use of syringes and needles which are contaminated  Mother to child during pregnancy, Labor and delivery and breastfeeding HIV can not be transmitted  Other body fluids: tears, saliva, Urine  Personal contact, social kisses  Social contact: eating from same plate  Inset bites: mosquitoes  Air or water  Others

13. Section 2-Magnitude of HIV/AIDS pandemic

14. Global Picture of HIV/AIDS Source: UNAIDS, 2006

15. Estimate Range People living with HIV/AIDS in 2007 33.2 million 30.6-36.1 million Adults living with HIV/AIDS in 2007 30.8 million 28.2-33.6 million Women living with HIV/AIDS in 2007 15.4 million 13.9-16.6 million Children living with HIV/AIDS in 2007 2.5 million 2.2-2.6 million Global picture

16. People newly infected with HIV in 2007 2.5 million 1.8- 4.1 million Adults newly infected with HIV in 20072. 1 million 1.4- 3.6 million Children newly infected with HIV in 2007 0.42 million 0.35-0.54 million AIDS deaths in 2007 2.1 million 1.9-2.4 million Adult AIDS deaths in 2007 1.7 million 1.6- 2.1 million Child AIDS deaths in 2007 0.33 million 0.31-0.38 million

17. Major HIV Indicators: National and Regional by Urban and Rural All Ages EthiopiaU+R Adult p (%)2004200520062007200820092010 Total 2.22.12.12.12.22.32.4 Male 1.71.71.71.71.81.81.9 Female2.62.52.52.62.62.82.9 HIV-pos population Total 891,862 901,893 929,699977,394 1,037,267 1,116,2161,216,908 Males 363,666 368,542 379,797399,376 424,452 457,373499,239 Females 528,196 533,351549,902 578,018612,815 658,843717,669 HIV-pos pregnant women69,77470,68671,85175,42079,183 84,18990,311 Annual HIV-pos births13,82013,97013,83614,14814,093 14,14014,276

18. Major HIV Indicators: National and Regional by Urban and Rural All Ages Ethiopia U+R New HIV infections Total115,527115,114122,971125,528125,147131,145 137,494 Males49,16250,50652,59053,49453,57055,75358,056 Females66,36564,60870,38172,03471,57775,39279,438 Adult HIV incidence (%)0.280.280.280.280.27 0.280.29 Annual AIDS deaths Total99,81499,36088,99771,90258,29044,75128,073 Males43,32842,99738,45931,15825,20619,31412,024 Females56,48756,36450,53840,74433,08425,43916,049 ART needs240,554242,453244,835258,264289,734336,160 397,818

19. Discuss the impacts of HIV?

20. Section 3- HIV and the Immune system Host: mounts HIV-specific immune responses  Cellular (cell-mediated) - most important  Humoral (antibody-mediated) Virus: subverts the immune system  Infects CD4 cells that control normal immune responses  Integrates into host DNA  High rate of mutation  Hides in tissue not readily accessible to immune system  Induces a cytokine environment that the virus uses to its own replicative advantage Achieved by “activation” of the immune system

21. Cells Infected by HIV Numerous organ systems are infected by HIV:  Brain: macrophages and glial cells  Lymph nodes and thymus: lymphocytes and dendritic cells  Blood, semen, vaginal fluids: macrophages  Bone marrow: lymphocytes  Skin: langerhans cells  Colon, duodenum, rectum: chromaffin cells  Lung: alveolar macrophages

22. Natural History of HIV Infection

23. Primary HIV Infection The period immediately after infection characterized by high level of viremia (>1 million) for a duration of a few weeks Associated with a transient fall in CD4 Nearly half of patients experience some mononucleosis-like symptoms (fever, rash, swollen lymph glands) Primary infection resolves as body mounts HIV- specific adaptive immune response  Cell-mediated response (CTL) followed by humoral  Patient enters “clinical latency”

24. Plasma RNA Copies CD4 Cells 4-8 WeeksUp to 12 Years2-3 Years CD4 Cell Count 1,000 500 Intermediate StageAIDS HIV Infection: Pathogenesis Viral set point Anti-HIV T-cell response Seroconversion Antibody response

25. Plasma RNA Copies CD4 Cells 4-8 WeeksUp to 12 Years2-3 Years CD4 Cell Count 1,000 500 Intermediate StageAIDS HIV Infection: Pathogenesis Typical Course OIs start here Anti-HIV T-cell response Sero-conversion Antibody response A lot of important stuff happens here

26. Opportunistic Infection: Definition Infections that develop as a result of damage to the immune system are called opportunistic infections or OIs These infections take advantage of the opportunity provided by a weakened immune system Infections tend to appear at predictable stages of immune deterioration

27. MAC, CMV, PML, PCNSL, Cryptococcus, Microsporidia, Toxo PCP CD4 Cells 4-8 WeeksUp to 12 Years2-3 Years CD4 Cell Count 1,000 500 CD4 Count and Opportunistic Infections 200 100 Bacterial Pneumonia, TB, HSV, Cryptosporidiosis Thrush, lymphoma, KS

28. Opportunistic infections Affects different body parts  CNS  GI  Skin and Mucosal surface  Respiratory system  Cardiac Pictures

29. Examples of OIs PCP Cryptococcal meningitis Toxoplasmosis etc.

30. HIV/AIDS Staging Combining the clinical manifestations and immunologic deterioration WHO suggested 4 stages of conditions I- IV Help in decision making regarding initiation of treatment or delaying treatment and many other prevention and care intervention

31. WHO Staging System for HIV/AIDS: Overview Tool used to guide management of HIV patient in resource limited settings with limited laboratory access Clinically based; CD4 count not required Simple, flexible and widely used Utilizes 5 clinical stages based on the degree of immunocompromise and prognosis  Primary HIV Infection, I,II, III, IV

32. WHO Staging System for HIV/AIDS: Overview Performed at each clinical visit  Diagnosis  Entry to clinical care (pre-ART)  Follow-up Stage assessment can be adjusted upwards or downwards over time according to response to ART and/or clinical progression

33. WHO Staging of HIV/AIDS Primary HIV Infection Stage I - asymptomatic Stage II - mild disease Stage III - moderate disease Stage IV - advanced immunocompromise

34. Primary HIV Infection (Acute HIV: A “Flu-like” Illness) Sudden onset, lasting from 3-14 days Clinical features:  Fever/sweats  Headaches, malaise, anorexia, sore throat  Lethargy, myalgias/arthralgias  Generalized LAN, “erythematous maculopapular truncal eruption” DA Cooper et.al., Lancet 1985;1:537.

35. JO Kahn & B Walker, N Engl J Med 1998;339:36.

36. WHO Stage I Asymptomatic or Persistent generalized lymphadenopathy (PGL)

37. Persistent Generalized Lymphadenopathy (PGL) Courtesy of Charles Steinberg MD

38. WHO Stage II Moderate unexplained weight loss (<10% of presumed or measured body weight) Recurrent respiratory tract infections (RTIs, sinusitis, bronchitis, otitis media, pharyngitis) Herpes zoster Angular cheilitis Recurrent oral ulcerations Papular pruritic eruptions (PPE) Seborrhoeic dermatitis Fungal nail infections of fingers

39. Pruritic Papular Eruption Courtesy of Charles Steinberg MD

40. Pruritic Papular Eruption Courtesy of Charles Steinberg MD

41. Apthous Ulcer Source: www.HIVdent.org. Copyright © 1996-2000 David Reznik, D.D.S.

42. Herpes Zoster Courtesy of Tom Thacher, MD Courtesy of the Public Health Image Library/CDC

43. Herpes Zoster Courtesy of Samuel Anderson, MD

44. Molluscum Contagiosum

45. WHO Stage III Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations  Severe weight loss (>10% of presumed or measured body weight)  Unexplained chronic diarrhea for > one month  Unexplained persistent fever (intermittent or constant for > one month)  Oral candidiasis  Oral hairy leukoplakia  Pulmonary tuberculosis (TB) diagnosed in last two years  Severe presumed bacterial infections (e.g. pneumonia, empyema, pyomyositis, bone or joint infection, meningitis, bacteremia)  Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis

46. WHO Stage III cont…. Conditions where confirmatory diagnostic testing is necessary  Unexplained anemia (<8 g/dl), and or  neutropenia (<500/mm3) and or  thrombocytopenia (<50 000/ mm3) for more than one month

47. Oral Candidiasis Courtesy of Samuel Anderson, MD Courtesy of Dr. R. Ojoh

48. Oral Candidiasis (2) Source: http://members.xoom.virgilio.it/Aidsimaging

49. Oral Hairy leukoplakia Courtesy of Dr. R. Ojoh

50. Pyomyositis Courtesy of Samuel Anderson, MD

51. WHO Stage IV Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations  HIV wasting syndrome  Pneumocystis pneumonia  Recurrent severe or radiological bacterial pneumonia  Chronic herpes simplex infection (orolabial, genital or anorectal of more than one month’s duration)  Oesophageal candidiasis  Extra pulmonary TB  Kaposi’s sarcoma  Central nervous system (CNS) toxoplasmosis  HIV encephalopathy

52. WHO Stage IV (2) Conditions where confirmatory diagnostic testing is necessary:  Extra pulmonary cryptococcosis including meningitis  Disseminated non-tuberculous mycobacteria infection  Progressive multifocal leukoencephalopathy (PML)  Candida of trachea, bronchi or lungs  Cryptosporidiosis  Isosporiasis  Visceral herpes simplex infection

53. WHO Stage IV (3) Conditions where confirmatory diagnostic testing is necessary:  Cytomegalovirus (CMV) infection (retinitis or of an organ other than liver, spleen or lymph nodes)  Any disseminated mycosis (e.g. histoplasmosis, coccidiomycosis, penicilliosis)  Recurrent non-typhoidal salmonella septicemia  Lymphoma (cerebral or B cell non-Hodgkin)  Invasive cervical carcinoma  Visceral leishmaniasis

54. Severe Chronic Herpes Simplex Ulcers © Slice of Life and Suzanne S. Stensaas

55. Disseminated Cutaneous Cryptococcosis Courtesy of Samuel Anderson, MD

56. Disseminated cutaneous cryptococcosis (2) Courtesy of Samuel Anderson, MD

57. HIV wasting syndrome Weight loss >10% body weight plus Unexplained chronic diarrhea (>1 mo) or Unexplained fever (>1 mo) plus chronic weakness

58. Exercise Photos/staging

59. Section 4-Preventing HIV Prevention from non sexual route of transmission  Screening of blood and blood products  Standard Precaution for health care providers and other care givers Prevention from sexual route of transmission  No contact with semen or vaginal secretions. Prevention of Mother to child transmission of HIV

60. PMTCT Majority of the children infected with HIV got it through MTCT Transmission of HIV occurs during pregnancy, Labor and delivery and breast feeding Comprehensive approach: need to be used in order to reduce MTCT Four Prongs_PMTCT Four Prongs_PMTCT

61. Primary prevention of HIV Prevention of unintended pregnancy on infected women Prevention of HIV from infected women to their infants Treatment care and support of infected women, infants and families

62. Exercise prevention methods Condom use

63. Section 5- Basics of ARVs What are:  ARVs ?  ART?  HAART? The goal of ART is to reduce the number of virus in the blood and increase the number of CD4 as much as possible

64. Basics of ARVs ARV stands for Ante Retro Viral Drugs ART the use of ARV drugs is called ARV Therapy in Short ART HAART: The use of Combination of at least three effective ARV drugs is known as HAART: Highly Active Ante Retroviral Therapy

65. History of ART In 1986 AZT was discovered as the first ARV drug  Reduced viral replication  Effect short lived due to the rapid development of resistance Dual therapy showed better results than monotherapy  Effect still limited by resistance In 1996, HAART was introduced  Sustained clinical and virological response seen

66. What is HAART? HAART stands for Highly Active Anti Retroviral Therapy Similar to ART (can be used interchangeably) A combination of at least three effective ARV drugs Controls HIV replication with reduced risk of resistance development However, it does not eliminate the virus from the body. It is not a cure

67. Goals of HAART- Primary Reduce HIV RNA (viral load) to undetectable levels within 4-6 months of ART initiation with durable suppression Increase CD4 cell count, allowing preservation or improvement of immune function Reduce HIV related morbidity thereby improving quality of life of the patient Reduce HIV related mortality

68. Goals of HAART- Secondary Reduction of the incidence of HIV by:  Increasing uptake of HCT  Prevention of mother to child transmission  Reducing stigma and discrimination through raising community’s hope  Reducing transmission of HIV at the community level

69. Groups of ARVs and Eligibility Groups  NRTIs  NNRTIs  PI

70. ARVs and the HIV Lifecycle

71. Antiretroviral Drugs

72. Ethiopian ART Guideline First LineSecond Line AZT or d4T and 3TC and NVP or EFV ABC, TDF, or AZT and ddI and Lop/r, SQV/r, NFV, IND/r

73. Side Effects Yellow eyes Change s in fat Skin rash Nausea, vomiting, diarrhea Abdominal pain Tingling or numbness in feet or hands More on Side Effects

74. When to Start ART Starting Antiretroviral Drugs is NOT AN EMERGENCY! Criteria for initiation must be met At least two visits are necessary before initiation to ensure patient readiness

75. Indications for ART Based on ‘Guidelines for Use of Antiretroviral Drugs in Ethiopia,’ January 2005.  Adapted from the revised WHO guidelines  Can be used in the presence or absence of CD4 values  Uses WHO clinical staging, CD4 count and TLC as appropriate

76. Clinical Criteria for ART Initiation for Adults (eligibility) If CD4 count available:  WHO stage IV irrespective of CD4  WHO stage III with CD4 ≤ 350/mm3  CD4 < 200/mm3 irrespective of the clinical stage If CD4 count not available:  WHO stage IV irrespective of TLC  WHO stage III irrespective of TLC  WHO stage II with TLC < 1200/ mm3

77. Exercise