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4th stage اسماعيل.د Medicine Lec-1 /2015 AIDS Acquired immunodeficiency syndrome 36.9 million [34.3 million–41.4 million] people globally were living with HIV (end 2014) 2 million [1.9 million–2.2 million] people became newly infected with HIV (end 2014) 1.21 million People died from AIDS-related illnesses (end 2014). New HIV infections have fallen by 35% since 2000. Worldwide, 2 million people became newly infected with HIV in 2014, down from 3.1 million in 2000. Definition: AIDS is a combination of signs and symptoms which occur together due to the HIV infection as well as many other infections as a result of the acquired immunodeficiency. Virology : HIV is a type of virus related to the group of retroviruses (RNA viruses). Like all viruses, it must invade the cells of other organisms to survive and reproduce. HIV multiplies in the human immune system's CD4+ T cells and kills vast numbers of the cells it infects. The result is disease symptoms. There are two forms of HIV: 1. HIV-1 is the more common and more potent form. This form of HIV has spread throughout the world. 2. HIV-2, which is less potent that HIV-1, is found predominantly in West Africa. It is also more closely related to two HIV-like viruses found in monkeys. There also are different strains of the virus, which makes it difficult to find one single vaccine. The virus contains 2 main enzymes: 1. Reverse transcriptase: to transcribe new RNA viral copies (viral replication). 2. Protease: important for protein synthesis (viral structure). 1 Cells affected : 1. CD4+ T-cells Count: Healthy adults usually have CD4+ T-cell counts (Helper) of 1,000 or more. Aids and some HIV sufferers have less than 200 CD4+ T-cells with abnormal function (cellular immunity). 2. Also affect the function of B-cells (Antibody production), Macrophages (phagocytic activity) and dentritic cells (modified macrophage). So the body will be invaded by different low and high virulent micro-organisms. Transmission : • HIV located in body fluids (Blood, breast milk, saliva, semen, tears, and vaginal fluids) The AIDS virus is transmitted from one person to another through several methods: 1. Blood or blood products 2. Mother to infant 3.Sexual contact (Hetero and Homo) 4. Sharing of needles or syringes Blood : • • • • Accidents in health care (i.e., needle stick or other medical instruments) Ear piercing Needle sharing with an infected person for any reason (IV drug needles [only minute amounts of blood are needed] Receiving a blood transfusion with infected blood (HIV screening of blood donation is applied in blood banks) HIV was transmitted through transfusions of contaminated blood or blood components, prior to the screening of blood for HIV infection and before the introduction in 1985 of heat-treating techniques to destroy HIV in blood products. The risk of acquiring HIV from transfusions today is extremely small. Sexual Contact : • The virus can be spread in body fluids including seminal and vaginal secretion • The infection can be spread from unprotected sex (sex without condoms) with an infected partner, including: Vaginal, Anal, and oral intercourse • and is spread from: men to men, men to women, women to men, women to women 2 Peri-natal HIV can be spread from Mother to infant during: • Birth (Peripartum) • Breast feeding • Pregnancy (Intrauterine) HIV has been detected in the saliva of infected individuals, however, no evidence exists that the virus is spread by contact with saliva. Tests show saliva has natural compounds that inhibit the infectiousness of HIV. No evidence has been found that the virus is spread to others through saliva such as by kissing. HIV has not been found to spread through: feces, sweat, tears and urine. There is no risk of transmission through: • sharing of bedding • sharing of food utensils • sharing of towels • swimming pools • Telephones • Donating blood when sterile needles are used • Touching an HIV infected person • or through touching objects such as: • clothes • door knobs • toilet seats Diagnosis : 1. The Standard HIV/AIDS Test: measures antibodies that are generated in response to the infection. Antibodies take time to develop (8 – 12 Ws), so in the very early stages of infection there may be a negative antibody test even though the person can be infected. The standard blood test for HIV also is negative in persons with acute HIV infection. 3 Two main serological tests are available: A. ELISA test: is simple, easy, cheap, low false negative and rapid. This test is the initial test that is performed in every suspected case or as screening test. B. If the above test is positive the next test is performed and called “Western blot test” to confirm the diagnosis. 2. PCR In the neonate with positive mother, the presence of antibodies in the serum is due to maternal antibodies and not always indicate infection in neonate (false positive) so another method is to detect viral Ag by using PCR (polymerase chain reaction) method. This is also important for diagnosis of early AIDS before antibodies are detected in the serum, and also useful in acute HIV infection. NOTE: HIV Self -Test Kit for home use is available and takes only 5 minutes. 3. After confirmation of the diagnosis you should do the CD4 T cell(T-Helper) count. Normally the number of cells are > 500cells/ml but in AIDS it will drop to < 200/ml. so that predispose the patient to numerous opportunistic infectious (mainly intracellular) like mycobacterium TB, viral and fungal infections. Clinical picture : 1. Following infection with HIV, a latent period (IP) of about 8-12 weeks during which the patient is asymptomatic and seronegative. 2. Seropositive stage/acute HIV infection (not AIDS): some patient develop acute symptoms for a short period of time (fever, malaise, headache, skin rash, lymphadenopathy, diarrhea, mouth ulcers and rarely encephalitis) which may persist for 10-14days. 3. A long period of asymptomatic phase which may extend up to 10 years in which the patient may develop no symptoms and looks normal. This is the most dangerous period in which the disease may be transmitted to others. 4. Some HIV positive develop persistent generalized lymphadenopathy (PGL): lymph nodes more than 1 cm in diameter in two sites for more than 3 months. 5. Acquired immunodeficiency syndrome (AIDS) (CDC Classification category C disease) is defined by the development of specified opportunistic infections, unusual tumours, when CD4 lymphocytes dropped to < 200 cells/ uL. The median interval from infection to the development of AIDS symptoms is around 7-10 years, although subgroups of patients exhibit 'fast' or 'slow' rates of progression. A. General symptoms and signs ( e. g. fever, fatigue, weight loss, diarrhea, oral candida, perianal herpes, splenomegaly, etc. B. Specific /AIDS defining or (HIV associated conditions):general symptoms and signs. Specific (HIV associated conditions): or disease (AIDS) defining conditions 4 HIV associated conditions: Infections • Disseminated cytomegalovirus infection • Chronic mucocutanous, disseminated herpes simplex infection. • Progressive multifocalleukcoencephalopathy • Extra-pulmonary tuberculosis. • Pneumocystis carinii pneumonia. • Disseminated mycobacterium avium intracellulare. • Candiasis of esophagus, bronchi or pulmpnary tree. • Extra-intestinal strongyloidiasis • Disseminated histoplasmosis • Other diseases Secondary neoplasms: kaposi’s sarcoma (in younger age), brain lymphoma, Burkitt's lymphoma and other non-Hodgkin Lymphoma . Every system or organ of the body may be involved (organ specific HIV disease) like skin, GIT, liver, nervous system (central and peripheral), heart, respiratory system and others can be a differential diagnosis of many diseases. الطبية الكتب في التفاصيل الى الرجوع الممكن من ANTIRETROVIRAL THERAPY (ART) The use of combination therapy, commonly referred to as highly active antiretroviral therapy (HAART), is now standard of care for HIV-infected patients requiring treatment. The introduction and widespread use of HAART has dramatically improved the prognosis for HIV-infected people. However, a variety of problems may limit the effectiveness of HAART in controlling HIV infection. There are 3 groups of drugs (antiretroviral drugs) 1. Nucleoside analogous: like Zidovudine and Lamivudine, Abacavir. 2. Protease inhibitors: like Ritonavir and Indinavir. 3. Non-nucleoside reverse transcriptase inhibitors: Like Loviride. 5 Combination of 2 or 3 drugs (HAART) are used to avoid drug resistance. The problem of drug toxicity and drug price also considered (usually the drugs are distributed free in poor countries) Treatment depends on the viral load (number of RNA copies) and the number of T helper (CD4+) lymphocytes. Most AIDS centers start therapy when the number of viral copies exceeding 10000/ml and number of T helper (CD4+) lymphocytes are less than 500 – 300/ml. 1. mild cases: combination of 2 drugs e. g. Zidovudine + Lamivudine 2. Moderate to severe cases: Combination of 3 drugs e. g. two nucleoside analogous and one protease inhibitor. The duration of treatment is unlimited. ANT-HIV drugs also can be used as a single drug prophylaxis e. g. for health care workers who had percutaneous exposure to HIV – infected blood. e. g. Zidovudine for short period. Prevention : 1. Unlike western countries; in Arabic and Islamic countries, the influences of religion, family and community are great and are the main factors against AIDS spread in such communities. 2. Public education and awareness about this disease and its squallies (medical, psychological and social). 3. Avoidness of illegal relationships. 4. In western countries and in many other countries in Asia and Africa where the sex practice is free; they speak about “safe sex practice” like using condoms and other measures. 5. Avoidness of needle exchange in drug addicts. 6. Screening of blood and blood product for HIV virus. In Iraq most of HIV positive cases are due to blood product transfusion especially in previous years when the screening for the virus in blood banks was not available. 7. no effective vaccine is available till now. 6