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Human Immunodeficiency Virus (HIV) By: Dr .Mona Badr As sistant 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 protein, (p24) 2. Env (envelop glycoproteins) ,gp120,gp41. 3. Pol (Reverse Transcriptase,protease,integrase) Structure of genetic Map of HIV HIV replication cycle Human Immunodeficiency Virus (Continued)  HIV is known to infect mainly T-helper cells(CD4), macrophages and monocytes that have(CD4)proteins on their surfaces.  Destroying T-helper cells(CD4)lead to severe immunologic impairment, leading to multiple opportunistic infections, unusual cancers and death. Human Immunodeficiency Virus Transmission: 1. Sexually:  By sexual contact with infected individual especially homosexual  The virus is present in semens 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 transplacentally(25%) ,but Treatment of the mother with antiviral therapy(Zidovudine) during pregnancy can reduce transmission in most cases.  Virus spread to child perinatally mainly (50%)during delivery given (Nevirapine) as single dose during delivery can reduce the transmission . breast feeding also an important way of peri natal 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& maculopapular rash.  Characterized by normal no of CD4 and the appearance of viral RNA in the blood (p24 ) core Ag followed by:  Appearance of two antibodies, one directed to the envelope(Anti-gp120) and the other to the core proteins(Anti-p24) start the chronic phase. 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 and anticore.  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:  Is present in 25-30% of patient who are otherwise asymptomatic.  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)  Anti-envelop (+ve) Anti-gp120.  Anti-core( –ve )Anti-p24 disappear from circulation. CD4 count decrease but still more than 200 x106 cells/L 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) 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)  Anti-core -ve (Anti-p24)  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 etc. infections e.g. Kaposi’s sarcoma) Blood markers:  HIV Ag p24  Anti envelop +ve(Anti-gp120) , Anti-core –ve (Anti-p24) 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 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  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 by electrophoresis env pol envelop protein reverse transcreptase HIV Ag p24: ( ELIZA)  To confirm the presence of the major protein of the core. 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 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  THANK YOU
 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                            