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HIV and AIDS

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HIV and AIDS

  1. 1. Pathophysiology: HIV and AIDS HIV = Human Immunodeficiency Virus (Initial Infection) AIDS = Acquired Immunodeficiency Syndrome (Sequale of HIV)  The first AIDs cases = in USA (1981)  34,000,000 people were living with HIV in 2010  1,800,000 people died of AIDS in 2010  Sub-Saharan Africa = Greatest Incidence of HIV HIV is thought to have originated from cross-species transfers from Chimpanzees in Central Africa – potentially through the Bush Meat Trade  Spread of HIV follows trucking routes around Africa. Transmission Transmission is Via Infected Body Fluids:  Blood  Serous effusions  Cerebrospinal fluid  Semen  Vaginal fluid  Breast milk Or other body fluids containing infected blood such as: Saliva, Vomit and Urine  Common routes of transmission The Virus  HIV is a Retrovirus (Genus = Lentivirus)  Its Features include: o Enveloped o Diploid o An RNA Virus (with a DNA intermediate)  There are two different types: 1. HIV-1 = Global Pandemic 2. HIV-2 = Mostly Western Africa  HIV-1 is more transmissible and associated with a faster rate of CD4 decline than HIV-2.  Both types of HIV contain the 3 Retroviral Genes: o Gag encodes for Inner Structural Proteins o Pol encodes for enzymes:  Polymerase  Integrase  Protease o Env encodes for the Viral Envelope:  On which is Glycoprotein 120 (Attaches to CD4 of host)
  2. 2. Immunology: 1. HIV infects human  Attaches to cells bearing the CD4 protein: o T- Helper Lymphocytes o Macrophages o Monocytes o Neural Cells 2. Uncoating: The Viral envelope fuses to host cell membrane and the Viral Nucleus is released from its’ Capsid into the Host’s Cytoplasm 3. Reverse Transcription: o An enzyme is created by HIV = Reverse Transcriptase o This enzyme is used by the Virus, to Reverse Transcribe its own RNA genomes into DNA that can be integrated into the host’s DNA. o So: HIV’s own RNA Genome  Reverse Transcriptase  Proviral DNA o NB: The above is ESSENTIAL to understand the main HIV drug mechanisms 4. Circularisation: This pro-viral DNA becomes circular (increases efficiency apparently) and migrates to the Host Cell nucleus. 5. Integration: The enzyme Integrase integrates the Proviral DNA into the cellular DNA 6. Transcription: Proviral DNA  Transcription by the Cell’s Polymerase  Proviral mRNA 7. Translation: Proviral mRNA  Translation by the Cell’s Ribosomes  Viral Proteins 8. Core Particle Assembly: o Viral Proteins  Transported to the Cell membrane Immature Virions o Polypeptide Precursors  Processed by Viral Protease  Mature Virus Particles 9. Budding: o Release of Mature Virus Particles and Immature Virions from Host Cell Following release: these new replications of HIV infect further CD4 cells. This whole process essentially has TWO effects: 1. Increases the Viral Load of HIV 2. Decreases the number of functional CD4 cells
  3. 3. Natural History: Clinically there are FOUR phases of HIV infection: 1. Acute HIV Infection 2. Asymptomatic HIV Infection 3. Symptomatic HIV Infections 4. AIDS defining Illness Acute HIV Infection  Also known as “Seroconversion”  2-4 weeks after initial exposure in 60% of sufferers  Similar symptoms to Glandular Fever   Serology = Negative or Indeterminate Asymptomatic HIV Infection  The virus is in balance with the immune system  The only sign may: o Generalised Lymphadenopathy  Varies in Length – average around 8 years Symptomatic HIV Infection  CD4 Count has started to fall – treatment level is <350cells/mm³  Viral Load is increasing steadily  Constitutional Symptoms o Fever and Diarrhoea  Opportunistic Infections   Always consider HIV in presentations that are: o Atypical o Recurrent o Severe AIDS defining Illness A diagnosis of AIDS depends on the TWO things: 1. CD4 Count: o 1 = CD4 of 500cells/mm³ o 2 = CD4 of 200-499cells/mm³ o 3 = CD4 of <200cells/mm³ 2. Clinical Stage: o A = Asymptomatic HIV o B = Symptomatic HIV o C = AIDS defining Diagnoses  AIDS is classified as any patient with:  A Combined Classification of: o C1 / C2 / C3 / A3 / B3 / C3  So basically anyone who has: o Ever had a CD4 count of <200cells/mm³ - whatever their current clinical state o Ever had an AIDS defining diagnosis – whatever their current CD4 count
  4. 4. Clinically it is important to check for co-infections with similar routes of Transmission: o Hepatitis C / B and Herpes Virus Key Points:  The greatest incidence of HIV infection is in Sub-Saharan Africa  The main HIV risk groups include: o Gay men, IV Drug Abusers, Sex Workers and Sub-Saharan Africans  HIV is an RNA Retrovirus, with a DNA intermediate to allow integration into Host Cells  The Virology of HIV is important to learn to understand HAART (Highly Active Anti-Retroviral Therapy – see David’s PBL)  HIV infection results in a reduced CD4 count predisposing to Opportunistic Infections  To diagnose AIDS a patient must have at one point had: o A CD4 count of <200cells/mm³ o An AIDS defining diagnosis References: 1. Sierra et al. Basics of the Virology and HIV-1and its Replication. Journal of Clinical Virology. Volume 34. Issue 4; 2005. 2. Dr N David. Clinical HIV Management. UEA Seminar; January 2012 3. Centres for Disease Control and Prevention (CDC). Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults; 1993 4. Medscape. HIV Disease. Available at: http://emedicine.medscape.com/article/211316-overview#a0101 5. Patient UK. HIV. Available at: http://www.patient.co.uk/showdoc/40000389/

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