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Human Immunodeficiency Virus By: Dr.Mona Badr Assistant Professor & Consultant Virologist College of Medicine & KKUH Human Immunodeficiency Virus Retroviridae family is divided into three subfamilies: Oncovirinae includes human T-lymphotropic virus types 1 & 2 (HTLV-1 Adult T-cell leukemia (HTLV-2 No human infection) Lentivirinae includes HIV 1 HIV2 Spumavirinae Worldwide AIDS (Pandemic) West Africa AIDS No human infection Human Immunodeficiency Virus (Continued) HIV consists of an outer envelope covered with glycoprotein spikes. An internal core genome consists of two identical ss-RNA genome of which enzyme reverse transcriptase is bound. The viral genome has 3-structural genes termed 1. gag core , 2. Env (envelop) 3. Pol (Reverse Transcriptase) Structure of genetic Map of HIV HIV replication cycle Human Immunodeficiency Virus (Continued) HIV is known to infect mainly T-helper cells and macrophages. Destroying T-helper cells results and severe immunologic impairment, leading to multiple opportunistic infections, unusual cancers and death. Human Immunodeficiency Virus Transmission: 1. Sexually: By sexual contact 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 and tooth brushes, nail cutters. Human Immunodeficiency Virus (Continued) Transmission: 3. From mother to child Infected mother transmit HIV to their babies in approximately 15-30% of cases. Treatment of the mother with antiviral therapy can prevent this in most cases. HIV is transmitted from mother to child ,in utero, during delivery or perinatally via breast feeding. 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 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 the appearance of HIV-Ag in the blood (p24 Ag core Ag) followed by: Appearance of two antibodies, one directed to the envelope and the other to the core proteins The Course of HIV-infection (Continued) 2. The chronic phase This phase totally asymptomatic, 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 and anti-core. CD4 counts are generally within normal limits (usually above 350 x106 cells/L) At the end of this stage, two syndromes appear: Persistent generalized lymphadenopathy (PGL) AIDS-related complex (ARC) The Course of HIV-infection (Continued) A. Persistent Generalized Lymphadenopathy: Is present in 25-30% of patient who are otherwise asymptomatic. Enlarged lymph nodes (at least 1 cm in diameter), in two or more non-contagious extra-inguinal sites, persisting for at least 3-months in the absence of any other illness or medication known to cause enlarge lymph node Blood markers: HIV Ag p24 (indicate active viral replication) Anti-envelop +ve Anti-core –ve CD4 count but still >200 x106 cells/L The Course of HIV-infection (Continued) B. AIDS-related complex (ARC): Are indicative of a defect in cell-mediated immunity and often manifested as candidiasis(oral thrush) seborrhoeic dermatitis,and disseminated zoster (shingles). .constitutional symptoms; Fever, diarrhea persisting more than a month with weight loss greater than 10% (Slim disease), night sweat, fatigue and malaise Neurological disease as myelopathies and peripheral neuropathy. The Course of HIV-infection (Continued) Blood markers: HIV Ag +ve( p24 indicate active viral replication) Anti-envelop +ve Anti-core -ve Decrease count of 200 x106 cells/L CD4 but still more than The Course of HIV-infection (Continued) Blood markers: HIV Ag +ve( p24 indicate active viral replication) Anti-envelop +ve Anti-core -ve Decrease count of 200 x106 cells/L CD4 but still more than 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 (Kaposi’s pneumocystis carinii pneumonia, toxoplasmosis of brain, disseminated or extra pulmonary mycobaceriosis etc. infections e.g. sarcoma) Blood markers HIV Ag +ve( replication). p24 . Anti-envelop +ve Anti-envelop +ve . indicate active viral Slim disease Kaposi’s sarcoma Kaposi’s sarcoma Kaposi’s sarcoma Pneumocystis pneumonia Laboratory Diagnosis Screening Elisa HIV-antibody Confirming W.B. Riba HIV Ag p24 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(twice) 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 gag core protein env. envelop Protein pol reverse transctpise HIV Ag p24: To confirm the presence of the major protein of the core. PCR: For detection of HIV RNA in the blood by using reverse transcriptase. Treatment Treatment does not eradicate the virus, but suppress the HIV replication. Treatment, should continue all life The aim of treatment is to maintain the immune system of the treated 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 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 Significant reduction in mother-to –child HIV transmition if ZIDOVUDINE is given during pregnancy OR NEVIRAPINE given as a single dose during delivary.