1. Seminar Presentation onHIV ITS PREVENTION AND CONTROL Edited By Emmanuel Godwin 5th Year Medical Student College of Medicine University of Nigeria , Enugu Campus 1.6181

2. PRESENTERS Emmanuel Godwin Ejezie Tobenna Ekpemiro Uchechi Duru Nancy Egwuatu Emmanuel 1.6182 3. outline Introduction to HIV Epidermiology Etiology and Risk Factors Pathogenesis Clinical Features Diagnosis and Management Treatment and prophylaxis Prevention and control Visit to PEPFAR References 3 4. INTRODUCTION TO HIV Emmanuel Godwin 4 5. Human Immunodeficiency Virus Infection PRESENTATION5 6. Beginning of HIV/AIDS Thefirst published article related to AIDS was in 1981. The principal authors 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. 1.6186 7. 1.6187 8. 1.6188 9. 9 10. 10 11. 1.61811 12. 1.61812 13. 13 14. 1.61814 15. Discovery of HIV infection. In 1982, the term Acquired Immune Deficiency Syndrome is used for the first time. The name was designated by the CDC. 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 HLTVIII. 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. 14415 16. Dr. Luc Montagnier wins the Nobel Prize in Medicine in 200814416 17. What is Human Immune Deficiency Virus Family- RetroviridaeSubfamily-Lentivirus, which literally means slow virus - it takes such a long time to develop adverse effects in the body.This virus attacks the immune systemThere are two strains HIV 1 & HIV 2 1.61817 18. What is Human Immune Deficiency Virus These contain RNA, the genetic material of HIVThe 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.The virus infects and destroys the CD4 lymphocytes which are critical to the bodys immune response. 1.61818 19. History of HIV The HIV virus first came to light during the early 1980s.A number of healthy gay men in New York began to develop rare opportunistic infections & cancers, that were resistant to treatment.One such viral opportunistic infection is cytomegalovirus that causes blindness & inflammation of the colon 1.61819 20. HIV Origins Research teams in the U.S.A & France made independent research discoveries of the virus.French researchers discovered a virus linked to AIDS in 1983, they called it LymphadenopathyAssociated Virus (LAV)In 1984, American researchers isolated a virus that caused AIDS, calling it Human T-lymph tropic Virus type III (HTLV- III )These two viruses were later found to be the same virus - HIV 1.61820 21. HIV Origin The emergence of HIV & AIDS has resulted in countless debates as to where it originated from Its suspected that it originated from S.I.V (Simian Immunodeficiency Virus) SIV affects Monkeys1.61821 22. HIV Origins Certain strains of SIV closely resemble the two types of HIVHIV 1 was difficult to link with SIVIn 1999 SIVcpz closely related to HIV 1Originated from chimpanzees but it has significant differences from HIV-1HIV 2 closely related to SIVsmOriginated from the green monkey 1.61822 23. 14423 24. Family : Retroviridae Subfamily : Lentivirus RNA virus, 120nm in diameter Envelope gp160; gp120 & gp41 Icosahedral symmetry Nucelocapsid Outer matrix protein (p17) Major capsid protein (p24) Nuclear protein (p7)Diploid RNA with several copies of reverse transcriptase 1.61824 25. Retroviral Genes gag (group-specific antigen): makes the cone shape viral capsid. pol (polymerase): codes for viral enzymes reverse transcriptase, integrase, and viral protease. env (envelope): makes surface protein gp120 and trans membrane gp41, enabling HIV to fuse to CD4 cells. 14425 26. Genes Coding Structural Proteins gag 1 The gag gene core and shell expressed as p55 ( p18,- p17) cleaved as p15, p18,and p24 make up as viral core and shellp24 seen during early stages reappearance in the late stages exacerbation of disease 14426 27. Envelop glycoprotein's env 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. The gp120 antibodies are present till the death of the patient. 14427 28. Polymerase reverse transcriptase pol The pol gene codes for the polymerase reverse transcriptase and other viral enzymes Expressed as precursor protein which is cleaved into proteins p31, p51,and p66 1.161828 29. Other genes Tat The Tran activator gene influences the function of genes some distance away. It controls transactivation of all HIV proteins. rev The differential regulator of expression of virus protein genes. vif The virus infectivity factor gene is required for infectivity as cell-free virus. nef The negative regulator factor retards HIV replication. vpr The virus protein R gene has an undetermined function.. 14429 30. Genes differ HIV I for HIV II vpu The virus protein U gene is required for efficient viral replication and release. It is found only in HIV-1. vpx The virus protein X gene has an undetermined function. It is found only in HIV-2 and SIV. 14430 31. Types of HIV14431 32. 1.61832 33. Epidemiology of HIV/AIDS Ejezie Tobenna K. 432Hz33 34. Epidemiology of HIV HIV is a global pandemic, as of 2011 approximately 34million people had HIV worldwide. Of these approximately 17.2million are men, 16.8million are women and 3.4million are less than 15 years of age. Sub-saharan Africa is the region most affected with HIV. South Africa has the highest population of people living with HIV of any country in the world with about 5.9million.34 35. In Nigeria, about 3.1million people are living with HIV and about 300,000 new infections occur annually with people between the ages of 15-24 contributing to 60% of the infection. Prevalence between women of 15-24 years of age is estimated to be three times higher than that of men of the same age, females constitute about 58% of persons living with HIV in Nigeria. Research shows that Benue state has the largest number of people living with HIV in Nigeria. In Enugu state, a greater percentage of people living with HIV are said to be found in Nsukka area of the state for reasons not really understood. 1.61835 36. ETIOLOGY AND RISK FACTORS36 37. Aetiology and Risk factors of HIV/AIDS The causative agents of the disease are strains of two structurally and geographically relatively distinct retroviruses; HIV-1 and HIV-2 of which man is the only known reservoir. Amongst the various aetiological factors of HIV/AIDS, the following are the most important predisposing factors to HIV 1.Unprotected sexual intercourse (including anal and oral sex); rape, sexual assault, multiple sexual partners, homosexual practise. 2. Transfusion of unscreened and contaminated blood. 1.61837 38. 3. Use of unsterilized needles like syringes in clinical practise and blades of clippers as used in barbing saloons. Note that intravenous drug abusers are at high risk of infection cause of continuous puncturing of veins with same needles used by different individuals who also engage in the same practise. Sexually transmitted disease which produce open sores on the genitals which act as door ways to entry of the virus. Another very important risk factor is that of mother to child transmission which has caused an increase in HIV infected newborns. 1.61838 39. Pathogenesis of HIV infection Ekpemiro, C. C. U 40. Transmission Four fluids are essentially involved in the transmission of HIV. Blood , Breast milk, Semen, Vaginal fluid ( have a potential for high HIV load-exchange infection) [Tears, saliva, sweat, and urine have a low concentration of the virus( natural cpds that decrease the conc. & infectiousness of HIV)]. 41. Heterosexual intercourse with infected persons. Injections with infected needles Through blood or blood products Transplacental transfer from mother to child etc. (all involve tranmission of body fluids which contain lymphocytes to which HIV attaches and more or less becomes a vehicle for transmission) 42. HIV is not transmitted by Handshakes, hugging, use of the same feeding utensils, sharing of conveniences (toilets) etc. 43. HIV virus contains numerous external spikes formed by two major envelope proteins;the external gp120 and the transmembrane gp41 [ both responsible for cell attachment and entry]. Has genes that encode the structural proteins of the virus: structural gene [gag] the enzymes responsible for reverse transcription and integration -Polymorphic gene [pol] the envelope glycoprotein- envelope gene [env] 44. Life cycle BINDING [gp 120 to CD4 surface protein rc]FUSION-of viral membrane to host cell membrane[ virus binds to ccr5 orcxcr4 coreceptors]ENTRYuncated viral rnaReverse transcriptase integraseVIRAL RNA or mRNA [viral in host cell] reprogramsPRO-VIRAL DNATranslationDs-DNA[integration into host chromosomal DNA-Proviral DNA ENVELOPED VIRUSBudding off host membrane Proteinbuilding blocksSmaller protein Protease- viral peices enzymeViral core [RNA-viral+enzymes+protein assembly pieces] 45. Each point in the life cycle of HIV is a real or potential target for therapeutic intervention.Hallmark of HIV infection is immunodeficiency! 46. Antibodies to HIV are produced invariably within 8 weeks of onset of primary infection. Detection of these antibodies forms the basis of most diagnostic screening test. 47. Phases in HIV infection Acute Clinical syndrome : initial infection with HIV Non specific symptoms lasting 1-3 wks.Phase of asymptomatic infection Period btw infections and onset of clinical symptoms( clinical latency) 2-15yrs not static , Persistent replication of virus, gradual decline in function and number of CD4+ T-cells. This stage marks the establishment of chronic and persistent infection which is the hallmark of HIV infection. 48. Early Symptomatic disease phase: onset of minor opportunistic infections. Mild bacterial, fungal, & viral infections but with longer duration than in healthy people. ARC or Pre-AIDSOnset of definite AIDS; Onset of AIDS opportunistic infections which are life threatening. They include disease of body organs, secondary neoplasm, infectious disease, constitutional neurologic disease. 49. Progression ( depends on response rate) Rapid Progressors: Median time from HIV to AIDS approx 10yrs. Some before 5yrs.Typical progressors: Currently considered long term survivors 1015yrs initial infections at this time most have immunodeficiency & opportunistic infections. Some have CD4+ T-cell count below 200/ul 50. Non progressors ( 5%): infected for a long time(10yrs), normal CD4+ counts, stable, never received antiretroviral therapy = long term nonprogressors. 51. Clinical features There are four clinical stages which encapsulates some of the clinical features in HIV disease Clinical stage 1 Asymptomatic Generalised lymphadenopathy Acute (primary) HIV infection Performance scale 1: asymptomatic, normal activity 52. Clinical stage 2 - Weight loss < 10% of body weight - Minor mucocutaneous manifestation (seborrheic dermatitis, prurigo, finger nail infections, recurrent oral ulcerations, angular cheilitis) Herpes zoster within the last five years - Recurrent upper respiratory tract infections Performance scale 2: symptomatic, normal activity 53. Seborrheic dermitits 54. Clinical stage 3 Weight loss > 10% of body weight Unexplained chronic diarrhoea > 1 month Unexplained prolonged fever > 1 month Oral candidiasis (thrush) Oral hairy leukoplakia Pulmonary tuberculosis within the past year Severe bacterial infection (ie pneumonia, pyomyositis Performance scale 3: bedridden 55. Clinical stage 4 -HIV wasting syndrome -Pneumocystic carinii pneumonia -Toxoplasmosis of the brain -Cryptosporidiosis with diarrhoea > 1 month -Cryptococcosis extrapulmonary -Cytomegalovirus disease of an organ other than liver, spleen or lymph node (eg retinitis) -Herpes simplex virus infection, mucocutaneous (> 1month) or visceral. -Progressive multifocal leucoencephalopathy -Any disseminated endemic mycosis -Candidiasis of esophagus, trachea, bronchi. -Atypical mycobacteriosis, disseminated or lungs -Non-typhoid salmonella septicaemia. -Extra pulmonary tuberculosis -Lymphoma -Kaposis sarcoma -HIV encephalopathy Performance scale 4: Bedridden >50% of the day during the last 56. KAPOSI SARCOMA 57. Really, is he the same person? 58. DIAGNOSIS AND MANAGEMENT OF HIV Duru Nancy A. 59. DIAGNOSIS OF HIV HIV can be diagnosed in the laboratory by - Antibody tests - Antigen detection methods. It is most commonly diagnosed by testing body fluids(usually blood) for the presence of antibodies to the virus. However, these tests are not accurate immediately after infection because it takes about 3week to 6months for these antibodies to be developed. A newer type of test which checks for the HIV antigen, a protein produced by the virus immediately 60. Clinical diagnosis may not be feasible except in advanced disease where HIV symptoms and associated complications are present. These may be a good pointer to the existence of the infection. 61. DIAGNOSIS OF HIV ANTIBODY TESTS: These includes: HIV Enzyme linked Immunosorbent Assay (EIA) cheap non specific Gives false positives Screening test Simple/Rapid HIV Test not expensive more Reliable simple Western blot(immunoblot) test: Very reliable Sensitive and specific Confirmatory test 62. ANTIGEN DETECTION TESTS- detects virus in blood sample. Viral culture- time consuming and expensive DNA Polymerase Chain Reaction(PCR) RNA PCR(viral load)- most sensitive thetest of choice in children less than 18 months because maternal antibodies persists for 1518months of age. The test is best done within 23months of life in non-breastfeeding infants, and 3months after cessation of breastfeeding. Also recommended for patients in the window period (2-12wks) 63. HIV COUNSELLING AND TESTING Pre-test counselling -discuss purpose of test -explore knowledge of the disease and risk assessment, transmission and reduction -explain test procedure and obtain informed consent from client. Testing Screening test : if negative, repeat test 3months afterwards if positive, confirm using two different immunoassays or western blot. Post-test counselling - if negative, discuss transmission and behavioural modification, advice to repeat test 3months afterwards. -if positive, explain significance and implication, organize urgent medical follow up, discuss confidentiality issues, provide practical support. 64. MANAGEMENT OF HIV 65. MANAGEMENT OF HIV This involves the treatment of the virus and prevention of opportunistic infections. The aim is to prevent the immune system from deteriorating to the point that opportunistic infection s becomes more likely. Treatment does not eradicate the virus 66. MANAGEMENT OF HIV HISTORY TAKING Assess time of HIV acquisition: previous negative test, previous antenatal screening, history consistent with seroconversion, known HIVinfected sexual partner, presence of HIV indicator disease Recreational drug use Occupation, residence, birthplace, travel history Past STIs Partners and children Past History of TB or any HIV indicator disease Immunization History BCG, Hep B and C Review of systems 67. CLINICAL EXAMINATION General: fever, generalised rashes, skin lesions, dry cough/tachypnoea, weight loss, generalized lymphadenopathy, jaundice, dermatitis. Eye: uveitis , retinitis Mouth and Oropharynx: White patches( oropharyngeal candidiasis, hairy leukoplakia), aphthous ulcers, herpes simplex infections. Gingivitis or periodontitis may be seen on the teeth. Chest : dull percussion, crepitations Abdomen: hepatosplenomegaly Anorectal region: rashes, ulcer, anal cancer, herpes Simplex CNS: Meningeal symptoms, dementia, Primary lymphoma, peripheral neuropathy. 68. Oropharyngeal candidiasisOral Hairy Leucoplakia 69. Anal Ulcers 70. INVESTIGATIONS CD4 count Viral load Hep B and C status HIV resistance test Toxoplasma and CMV IgG antibody(annually if negative initially) Treponema serology Urinalysis Liver function testFull blood count. Serum electrolyte, Urea, creatinine Lipid profile Chest X-ray Dilated fundoscopy Cervical smear for women(yearly is normal at previous test) STI sreen 71. Dilated fundoscopy 72. TB-HIV COINFECTIONTB In Immunocompetent patients. 73. In UNTH, the tests routinely done are: viral load, CD4 count, SEUCr, FBC Liver function tests, hep B and C, Chest X-ray. These tests are repeated 6monthly. Patient is seen 1month after samples are taken for the test on the 1st visit for possible commencement of therapy. Abnormal test results may contraindicate the administration of certain drugs A chest x-ray suggestive of TB co-infection may require patient to be seen by the Chest Unit where the DOTs therapy is administered for at least 2wks before commencement antiretroviral therapy. 74. The cornerstone In the management and treatment of HIV is the Highly Active Antiretroviral Therapy(HAART). It involves multiple drug therapy. The principle of combining drugs serves to provide additive antiviral activity and reduction in emergence of viral resistance. The decision to start therapy is dependent on several factors of which the CD4 count is the most important. Research data led the US guideline in 2011 to recommend the initiation of ART in patients with CD4 count threshold of 350cells/microL or in patients with a history of AIDS defining illness. 75. 2013 guidelines from WHO now however recommends that a threshold of 500cells/microL. It also states that ART should begin immediately regardless of CD4 count, in HIV positive serodiscordant couples, patients with Hep B co-infection, HIVAssociated nephropathy, pregnant and breastfeeding women and children under 5years. Choice of drugs made based on -virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug reaction potential, co-morbid conditions, drug resistance test results. 76. TREATMENT, PR EVENTION AND CONTROL OF HIV INFECTION Egwuatu, Emmanuel C. 77. TREATMENT The standard for treatment of HIV infection & PMTCT is the Combination HAARTHAART (Highly Active Antiretroviral Therapy)-is a combination of about 3diff. drugs from diff. classes of ARV drugs(atleast 2 diff grps eg 2 NRTIs + 1 NNRTIs)CLASSES OF ARV DRUGS:1.Reverse Transcriptase Inhibitors:-NRTIs Zidovudine,stavudine,lamivudine, didanosine, abacavir, zalcitabineNNRTIs- Nevirapine, EfavirenzNtRTIs-Tenofovir2. Protease Inhibitors:Saquinavir, retronavir, indinavir, nelfanavir.3. Entry inhibitors enfuvirtide,maraviroc.4. integrase inhibitors raltegravirN/B : The most widely used ARV drugs in Nigeria, which are approved by NAFDAC are those in the class of reverse transcriptase inhibitors & protease inhibitors. WE HAVE NO CURE FOR HIV/AIDS presently!!!!. 78. Adult Regime & Dosages : 1st line drugs used in Nigeria viz: Zidovudine, stavudine,lamivudine, nevirapine, efavirenz. These are used under the ff fixed combination : stavudine (dt4)+ lamivudine(3TC) + nevirapine(NVP) zidovudine(AZT)+ lamivudine (3TC) + nevirapine(NVP) Doses of these 1st line drugs given: Stav(dt4) --40mg 2x daily (30mg if < 60kg) Zido(AZT) --250-300mg 2x daily Lami(3TC) --150mg 2x daily Efavirenz(EFV) --600mg x1 daily Nevirapine(NVP) : 1st 2wks -200mg x1 daily if no rxn 200mg x2 daily 79. Choice and onset of ART depends on : Clinical condition of the patient(+ knowledge of side effect of the ARV drugs) CD 4+ cell count(>350 cells/mm) Clinical staging (esp stages 3 & 4)Childrens regime & dosages:Both children and adolescents are best managed by a specialist in paed. HIV infection & a multidisciplinary approach shld be employed due to the peculiarites of HIV /AIDS mgt in children. The onset of ART depends on the stage & age of the child;this can be started in the ff: All HIV+ve children(24mths with WHO stages 3&4(regardless of CD 4 count) All HIV+ve children aged 24-59 mths with CD4 count