Hiv

• AIDS


  Acquired Immunodeficiency Syndrome
• Topics covered


  • Biochemistry of the Virus
  • Spread
  • Detection
  • Drug treatment
• Structure of HIV


  • Approximately 100 nm in diameter
  • Has an envelope of lipids, which embeds the gp41 trimeric transmembrane glycoprotein
  • The gp120 surface glycoprotein is attached to the envelope
  • Core proteins p6, p24, p17 (matrix protein), and p7 (nucleocapsid protein) are encoded by the viral gag gene
• Viral genome


  Two copies of ~10 kilobase (kb) positive-sense viral RNA genome, with integrase, protease and reverse transcriptase enzymes
• Other HIV proteins


  • vpr (viral protein R)
  • vif (viral infectivity protein)
  • nef (negative regulatory factor)
  • rev (regulator of viral protein expression)
  • tat (transactivator of transcription)
• HIV targets


  Human immune system, particularly CD4+ T cells, dendritic cells and macrophages
• CD4+ T cell count declines below a critical point


  Cell-mediated immunity is lost, body becomes susceptible to opportunistic infections, resulting in AIDS
• Difference between HIV-1 and HIV-2

  • They are genetically distinct, with only 55% sequence identity
  • HIV-2 tends to develop more slowly than HIV-1
  • HIV-2 has a lower mortality rate than HIV-1
• Methods of HIV transmission

  • Sexual intercourse
  • Use of contaminated syringes, needles and other piercing instruments
  • Use of contaminated blood and its products, organs and tissues
  • Mother to child transmission (MTCT)
• HIV infection cycle in CD4 cells

  1. Entry and binding

  2. Reverse transcription

  3. Integration

  4. Replication

  5. Budding and maturation
• Progression of HIV-1 vs HIV-2

  • HIV-2 is less likely to progress into AIDS due to lower transmissibility
  • HIV-2 infections have lower viral loads and more protective immune response, slowing disease progression
• Types of HIV tests

  • Antibody tests
  • Antigen/antibody tests
  • Nucleic acid tests (NAT)
• Antibody tests


  Look for antibodies to HIV, can take 23 to 90 days to detect HIV after exposure
• Antigen/antibody tests


  Look for both HIV antibodies and antigens, can detect HIV 18 to 45 days after exposure
• Nucleic acid tests (NAT)

  Look for the actual virus in the blood, can detect HIV 10 to 33 days after exposure
• Goals of HAART (Highly Active Antiretroviral Therapy)

  • Reduce morbidity and mortality
  • Improve quality of life
  • Reduce plasma viral RNA load
  • Prevent transmission to others
  • Prevent drug resistance
  • Improve immune function
• How HAART reduces HIV transmission

  Reduces HIV-1 RNA levels, which reduces the risk of sexual transmission to partners to nearly zero
• Main classes of HAART agents

  • Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
  • Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
  • Protease inhibitors (PIs)
  • Integrase Strand Transfer Inhibitors (INSTIs)
  • Fusion inhibitors (FIs)
  • Chemokine Receptor Antagonists (CCR5 Antagonists)
• NRTIs


  Nucleoside or nucleotide analogs that inhibit viral replication by causing premature DNA chain termination
• NNRTIs


  Bind to HIV reverse transcriptase at an allosteric site, causing a stereochemical change that inhibits DNA polymerase
• Protease inhibitors (PIs)


  Competitively inhibit the proteolytic cleavage of the gag/pol polyproteins, resulting in immature, non-infectious virions
• Integrase Strand Transfer Inhibitors (INSTIs)


  Bind viral integrase and prevent viral DNA from being incorporated into the host cell chromosome
• Fusion inhibitors (FIs)


  Bind to the envelope glycoprotein gp41 and prevent viral fusion to the CD4 T-cells
• Chemokine Receptor Antagonists (CCR5 Antagonists)

  Selectively and reversibly block entry into the CD4 T-cells by preventing interaction between CD4 cells and the gp120 subunit of the viral envelope glycoprotein