HIV

• Immunodeficiencies


  Uncommon, chronic and severe disorders of the immune system where the body cannot mount a sufficiently protective immune response, leading to an increased susceptibility to infections
• Types of immunodeficiencies


  • Congenital - inherited defective genes or absence of genes necessary for immune system function
  • Acquired - caused by a variety of drugs, cancers, infectious agents or environmental exposure to toxins
• Viruses capable of infecting and killing lymphocytes


  e.g. Hodgkin's Disease, AIDS
• DiGeorge Syndrome (DGS)


  Also known as 22q11.2 deletion syndrome, caused by a small deletion in chromosome 22 at position 22q11.2 leading to abnormal development of certain cells/tissues, impaired T-lymphocyte production, low T-lymphocyte numbers, frequent infections, distinctive facial appearance, congenital heart disease, hypocalcemia
• Hodgkin's Disease (HD)


  A type of lymphoma (blood cancer) where lymphocytes grow abnormally and spread, making it difficult for the body to fight infections. Main cause is unknown but linked to DNA mutations and Epstein-Barr virus (EBV), most common in ages 15 to 40 and over 55. Symptoms include swelling of lymph nodes in the neck, armpit, groin that is not painful.
• Hodgkin's Disease (HD) treatment

  1. Chemotherapy and radiation

  2. Immunotherapy or stem cell transplant if chemotherapy/radiation doesn't work
• Hodgkin's Disease (HD) outlook

  Five-year survival rate ~86%, ten-year survival rate ~80%
• Human Immunodeficiency Virus (HIV)


  Pathogen that causes Acquired Immunodeficiency Syndrome (AIDS)
• HIV believed to have originally come from a virus particular to chimpanzees in West Africa, transmitted to humans through blood transfer during hunting


  1930s
• Rare types of pneumonia (Pneumocystis pneumonia), cancer (Kaposi's sarcoma), and other illnesses being reported by gay men and injection drug users, all with decreased immune function


  Early 1980s
• Pneumocystis pneumonia (PCP)


  Serious infection caused by the fungus Pneumocystis jiroveci, common member of the respiratory microbiome and an opportunistic pathogen that isn't hard to prevent and control unless you have a weakened immune system like HIV/AIDS
• Kaposi's sarcoma


  Tumor of the blood vessel walls caused by human herpesvirus-8 (HHV-8), rare in people not infected with HIV but common in HIV-positive people, appears as pink, red or purple lesions on the skin, mouth, and internal organs
• Realized that the HIV infection can be sexually transmitted


  1983
• Earliest reported AIDS-related death in Congo


  1959
• First AIDS-related death in the Western world


  1976
• HIV structure


  Two RNA strands, enzymes including reverse transcriptase, capsid, envelope with glycoprotein spikes called gp120
• HIV infection


  1. Attachment

  2. Fusion and entry

  3. Incorporation
• HIV as a retrovirus

  Type of RNA virus that inserts a copy of its genome into the DNA of the host cell it invades, changing the genome of that cell
• HIV life cycle


  Attachment to CD4 receptor and co-receptor, fusion and entry, reverse transcription, incorporation of viral DNA into host cell DNA as a latent provirus, production of new virions, release of new virions to infect more cells
• Characteristics of HIV that challenge the immune system

  • Retrovirus with reverse transcription leading to mutation and genetic variation, targets CD4 helper T-cells and macrophages important for the immune system, antigenic variability, induces fusion of infected cells with neighbouring cells
• Seroconversion


  The development of antibodies to HIV, occurs between one and two months after infection
• Antiretroviral therapy


  Can prevent progression to AIDS by decreasing viral load in an infected person
• Viral load


  The amount of virus in an infected person's blood, expressed as the number of viral particles per milliliter. Higher viral load indicates the infection is progressing.
• Stages of HIV infection

  • Asymptomatic - viral load increases, billions of CD4 T-cells infected, immune response depletes virus at first, persistent swollen lymph nodes
  • Symptomatic - early indications of immune failure, many latent viruses, persistent yeast infections, fever, diarrhea, shingles, joint pain
  • AIDS - opportunistic infections like respiratory tract infections, eye infections, TB, toxoplasmosis, Pneumocystis pneumonia, Kaposi's sarcoma, low CD4 cell count
• Normal CD4 T-cell count

  800-1000 cells/μL
• Asymptomatic HIV infection


  CD4 T-cell count above 500 cells/μL
• Need for HIV treatment

  CD4 T-cell count below 350 cells/μL
• AIDS diagnosis


  CD4 T-cell count below 200 cells/μL
• Understanding how HIV infection progresses in a host is integral to understanding the diagnosis, transmission, and prevention of this pandemic. Although there is no cure, there are drug treatments.
• Normal CD4+ T-cells count

  800-1000 cells/μL
• Below normal but above 500 CD4+ T-cells/μL


  Asymptomatic, in Phase 1
• Below 350 CD4+ T-cells/μL


  Indicates treatment is needed, in Phase 2
• Below 200 CD4+ T-cells/μL


  Has progressed to Phase 3, AIDS
• Stages of HIV Infection

  • Phase 1 - Asymptomatic
  • Phase 2 - Symptomatic
  • Phase 3 - AIDS
• CD4 (helper T-cell) count


  You want it to be high
• Viral load (amount of HIV in blood)


  You want it to be low
• Stage Progression


  1. Phase 1 - Viral load increases, billions of CD4+ T cells infected, immune response depletes virus at first, persistent swollen lymph nodes

  2. Phase 2 - Many latent viruses, persistent yeast infections, fever, diarrhea, shingles, joint pain, CD4+ cell numbers decrease

  3. Phase 3 - Opportunistic infections: respiratory tract, eye, TB, toxoplasmosis, Pneumocystis pneumonia, Kaposi's sarcoma, CD4+ cells low
• Understanding how the HIV infection progresses in a host is integral to understanding the diagnosis, transmission, and prevention of this pandemic
• Although there is no cure, there are drug treatments
• HIV infection often does not cause any immediate symptoms, but a person newly infected with HIV is infectious and can transmit the virus to another person