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Lect 10 - HIV disease and aids


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Lect 10 - HIV disease and aids

  1. 1. HIV Disease and AIDS Historical Background 1981 : Few reports about a rare disease in previously healthy homosexual men with high incidence of : •Loss of immune function •Unusual opportunistic infections •Certain malignant tumors 1982 : Word AIDS was used 1st time by CDC 1983 : Viral cause was identified that selectively infects Th cells Was named as HTLV-III Now named as HIV (Human Immunodeficiency Virus)
  2. 2. Epidemiology • Worldwide >33 millions infected with HIV • Number 1 killer in Africa • >20 millions have died of AIDS • 4th leading cause of death in the world after heart diseases, strokes & pneumonia • A new infection occurs every 6 seconds • A person dies of AIDS every 5 minutes HIV Disease and AIDS
  3. 3. Routes of Transmission & Persons at High Risk 1. Sexual contact o Homosexual men : major infected group 2. Blood & Blood Products o Drug abusers & o Hemophiliacs 3. Mother to infant o During child birth o Breast feeding HIV Disease and AIDS
  4. 4. Causative Agent • HIV-1 : in most parts of the world • HIV-2 : in most parts of Africa & India • Family : Retroviridae • Subgroup : Lentivirus HIV Disease and AIDS
  5. 5. Structure of virus Important antigens • Surface glycoprotein (gp120) o Partly responsible for attachment to host cells • Transmembrane glycoprotein (gp41) o Probably plays a role in entry of virus into cell • Matrix protein (p17) o Helps maintain viral structure HIV Disease and AIDS
  6. 6. Structure of virus The Core of Virion • Capsid antigen (p24) • Two copies of ssRNA • Nucleocapsid • Viral enzymes o Reverse transcriptase o Protease o Integrase HIV Disease and AIDS
  7. 7. Types of Human Cells affected • CD4+ Th1 cells : o Principal target of HIV o Main cause of immunodeficiency • CD4+ Th2 cells • CD4+ macrophages, dendritic & other APC o Are continuing source of virus • Several types of brain cells o Probable cause of lethargy & dementia • Intestinal epithelium & lymphoid tissues o Probably contribute to chronic diarrhea & weight loss
  8. 8. Attachment, Entry & Replication of virus inside host cell
  9. 9. HIGH GENETIC VARIABILITY IN HIV • Is due to high rate of error when reverse transcriptase copies viral genome • Variant viruses show differences in: o Their preferred host cell o Rate of replication o Response to host immunity • Enormously complicates the development of vaccine against HIV
  11. 11. CLINICAL FEATURES OF HIV DISEASE A. Acute Retroviral syndrome (ARS) • Incubation period 1-6 weeks • In 50-70% of HIV infected subjects • Sore throat & Fever • Myalgia & headache • Enlarged lymph nodes • Symptoms may last for 1-4 weeks • Self-limiting without treatment
  12. 12. B. Asymptomatic period • Lasts for months to years • A silent struggle goes on between HIV & immune system • The virus continues to be present in blood and body secretions – a threat to others • Level of CD+ lymphocytes slowly falls • Leads to AIDS CLINICAL FEATURES OF HIV DISEASE
  13. 13. C. AIDS • The immune system slowly loses battle • Peripheral blood CD+ count slowly falls • Symptoms of AIDS appear when count falls below 300 cells per ul (Normal count 1000 cells per ul) Incubation period • 10% - 5 years ; 90% within 17 years • Weight loss, fatigue, diarrhea, fever • Enlarged lymph nodes • Opportunistic infections • Malignant tumors CLINICAL FEATURES OF HIV DISEASE
  14. 14. Malignant Tumours Associated with AIDS • Kaposi’Sarcoma o Unusual tumor arising from blood or lymphatic vessels o Caused by herpes virus-8 o Strong association with immunodeficiency • B-Lymphocytic Tumors of Brain o 60-100 times more common in AIDS • Cervical & Anal Carcinomas
  15. 15. • Pneumocystosis : o Pneumocystis carinii • Toxoplasmosis : o Toxoplasma gondii • Cytomegalovirus Disease : CMV • Tuberculosis o M. tuberculosis & o M. avium-intracellulare complex • Candidiasis Opportunistic infections Associated with AIDS
  16. 16. Lab Diagnosis • anti-HIV Abs by ELISA: Easier to detect than virus itself • Confirmed by Western Blot & RIBA • PCR : to detect viral RNA
  17. 17. Mechanism of action of antiretroviral drugs NRTI (Nucleoside RT Inhibitors) •Ziduvudine •Stavudine NNRTI (Nonnucleoside RT Inhibitors) •Nevirapine •Delaviridine TREATMENT OF AIDS • A cocktail of drugs with different mechanisms of action • HAART “Highly Active Antiretroviral Therapy” • Specific treatment for opportunistic infections
  18. 18. • Health education • Detection & Treatment of the HIV-pos cases • Changing sexual behaviors • Disinfection of all blood samples • Chemoprophylaxis with Ziduvidine to o HIV-positive pregnant mother & o Newborn infants to HIV-positive mother • Treatment of opportunistic infections PREVENTION OF AIDS
  19. 19. HIV Vaccine Prospects • No approved vaccine is currently available • A vaccine that is a combination of two previously unsuccessful vaccine candidates was reported in September 2009 to have resulted in a 30% reduction in infections in a trial conducted in Thailand • Theoretically two approaches: 1. Preventive Vaccine o To immunize uninfected persons 2. Therapeutic vaccine o To boost the immunity of already infected persons o Like post-exposure treatment of rabies PREVENTION OF AIDS