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Human Immunodeficiency Virus (HIV) By: Dr .Mona Badr As sistant Professor & Consultant Virologist College of Medicine & KKUH Human Immunodeficiency Virus HIV consists of an outer envelope covered with glycoprotein spikes. An internal core genome consists of two identical ss-RNA transcriptase is bound. genome of which enzyme reverse Structure of genetic Map of HIV Human Immunodeficiency Virus (Continued) HIV is known to infect mainly T-helper cells(CD4), macrophages. Destroying T-helper cells(CD4)lead to severe immunologic impairment, leading to multiple opportunistic infections, unusual cancers and death. LATANCY infection. is known feature of HIV Human Immunodeficiency Virus Transmission: 1. Sexually: By sexual contact with infected individual especially homosexual The virus is present in semen and vaginal secretions 2. Parenterally: Direct exposure to infected blood and blood products. Use contaminated needles and syringes as in (drug abuser) and Tattooing. Through contaminated surgical and dental instruments. Sharing contaminated razors &tooth brushes, nail cutters. Human Immunodeficiency Virus (Continued) Transmission: 3. From mother to child (VIRTICAL TRANSMITION) Infected mother transmit HIV to their babies transplacentally(25%) ,but Treatment of the mother with antiviral therapy(Zidovudine) during pregnancy can reduce transmission in most cases. Virus spread to child prenatally mainly (50%)during delivery given (Nevirapine) as single dose during delivery can reduce the transmission . breast feeding also an important way of transmission (25%). Virus Inactivation HIV is easily inactivated by treatment for 10 min at 37oC with any of the following 10% house hold bleach, Sodium Hypochlorite 50% ethanol 35% isopropanol 0.5% Paraformaldehyde 0.3% hydrogen peroxide The Course of HIV-infection The course of HIV-infection can be divided into three stages: The acute phase The chronic phase 1- A(PGL) 2-B(ARC) AIDS The Course of HIV-infection 1. The acute phase Incubation period (1-4) weeks. Mostly asymptomatic, in 25-50% of cases patients may have symptoms resembling infectious mononucleosis or influenza like illness for short period. Characterized by normal no of CD4 and the appearance of viral RNA in the blood ( core Agp24) followed by appearance of two antibodies Anti-envelop(Anti-gp120) & Anti- core(Anti-gp24). The Course of HIV-infection (Continued) 2. The chronic phase totally asymptomatic This phase , which lasts for about 1-10 years in adults, 1-5 years in children. Characterized by the disappearance of HIV-Ag (p24) from circulation and the presence of anti-envelope (Anti-gp120) and anti-core(Anti-gp24). CD4 counts are generally within normal limits (usually above 350 x106 cells/L) At the end of this stage, two syndromes appear: Persistent generalized lymph-adenopathy (PGL) AIDS-related complex (ARC) The Course of HIV-infection (Continued) A. Persistent Generalized Lymphadenopathy: Enlarged lymph nodes (at least 1 cm in diameter), in two or more extra-inguinal sites, persisting for at least 3-months in the absence of any current illness or medication known to cause enlarge lymph node. Blood markers: HIV Ag p24 (indicate active viral replication) CD4 Anti-envelop (+ve) Anti-gp120.& but still more than 200 x106 cells/L count decrease The Course of HIV-infection (Continued) B. AIDS-related complex (ARC): Are indicative of a defect in cell-mediated immunity. Characterized by candidacies (oral thrush) and all symptoms and signs of AIDS, but lack the opportunistic infections as Pneumocytosis OR tumors as Kaposi sarcoma. ARC Characterized by: Fever, diarrhea persisting more than a month with weight loss greater than 10% (Slim disease), night sweat, fatigue and malaise Neurological neuropathy. disease as myelopathy and peripheral The Course of HIV-infection (Continued) Blood markers: HIV Ag +ve p24 (indicate active viral replication) Anti-envelop +ve(Anti-gp120) CD4 count decreased but still more than x106 cells/L 200 The Course of HIV-infection (Continued) 3. AIDS The end stage of the disease characterized by: Marked decrease in CD4 T-helper cells < 200 x 106 cells/L Severe immunologic impairment, cell mediated immunity Opportunistic Unusual cancers ( pneumocystis carinii pneumonia, toxoplasmosis of brain, disseminated or extra pulmonary myco-baceriosis . infections e.g. Kaposi’s sarcoma) Blood markers: HIV Ag p24 Anti envelop +ve(Anti-gp120) , Marked CD4 count less than 200 x106 cells/L Slim disease Kaposi’s sarcoma Kaposi’s sarcoma & Slim disease Kaposi’s sarcoma Pneumocystis pneumonia Laboratory Diagnosis Screening Elisa HIV-antibody HIV Ag p24 Confirming W.B. Riba PCR Laboratory Diagnosis By detection of both HIV-Ab and HIV-Ag, using EISA (screening test). If results are negative, report negative. If results are positive, repeat the screening test in duplicate Repeatedly reactive specimens, must be confirmed by Western blot and HIV-Ag test by Eliza. If the confirmatory results are negative, report negative If the confirmatory test results are positive, report positive Laboratory Diagnosis (Continued) Western Blot: To confirm the presence of Anti –HIV to the structural proteins of the virus by ELECTROPHORESIS. . PCR: For detection of HIV RNA in the blood plasma (viral load) this test is important for HIV diagnosis in infant of infected mother and also to monitor the antiviral treatment LABORATORY DIAGNOSIS Indeterminate results: Western blot indeterminate result, means that the test specimen not positive nor negative. The individual must be retested after 8-12 weeks. If the result is negative, report negative If the result is positive, report positive If the individual still indeterminate then he or she must be referred to medical evaluation The aim of medical evaluation is to look for signs and symptoms suggesting HIV-infection. Or PCR to look for HIV-RNA genome. Treatment Treatment does not eradicate the virus, but suppress the HIV replication. Treatment, should continue for all life The aim of treatment is to maintain the immune system of the patient near normal as possible At the present time the combined therapy is used two reverse transcriptase inhibitors pulse one protease inhibitor Treatment (Continued) A. Reverse Transcriptase Inhibitors: AZT Zidovudine ddC Zalcitabine ddI Didanosine d4T Stavudine 3TC Lamivudine All the above anti-viral drugs are nucleoside analogues. B. Protease inhibitors Saquinavir Indiniavir Ritonavir Nelfinavir Human Immunodeficiency Virus (VIRTICAL TRANSMITION) Infected mother transmit HIV to their babies transplacentally(25%) ,but Treatment of the mother with antiviral therapy(Zidovudine) during pregnancy can reduce transmission in most cases. Virus spread to child prenatally mainly (50%)during delivery given (Nevirapine) as single dose during delivery can reduce the transmission . breast feeding also an important way of transmission (25%). Treatment (Continued) Prevention & Control: There is no vaccine available yet for HIV Practice safer sex by having one sexual partner Do not share razors, tooth brushes, etc Do not share needles and syringes Avoid direct exposure to body fluids Educate the public about HIV-infection. THANK YOU GOOD LUCK