II. Pathophysiology

  1. HIV is a single-stranded RNA Retrovirus, a Sexually Transmitted Infection as well as bloodbourne pathogen
    1. HIV 1 is the most common worldwide HIV form and is the major cause of AIDS
    2. HIV 2 causes a similar presentation to HIV 1 and is found in South Africa and India
  2. HIV is a Retrovirus
    1. Virus that generates complementary DNA from RNA via reverse transcriptase enzyme
    2. Virus then inserts its DNA into the host DNA via integrase enzyme
  3. HIV Structure
    1. Outer wall of HIV is a lipid bilayer membrane
      1. Membrane contains embedded glycoproteins (gp120 is external, gp41 is transmembrane)
      2. P10 protease is present between this outer wall and the nucleus-like structure's capsid membrane
    2. Nucleus-like structure is surrounded by capsid wall (p17) and contains RNA and enzymes
      1. Two strands of single stranded RNA, each enclosed in a nucleocapsid (p24)
      2. Enzymes: p32 Integrase, p64 reverse transcriptase
  4. HIV Infection
    1. Fusion
      1. HIV gp120 binds to CD4 receptors on CD4+ T Cells (as well as Macrophages and dendritic cells)
    2. Proviral DNA generation
      1. Virus penetrates the host cells, with its RNA infiltrating the cytoplasm
      2. Complementary DNA (cDNA) is formed from HIV RNA via reverse transcriptase enzyme
      3. cDNA penetrates the host cell's nucleus and integrates with host DNA via HIV integrase enzyme
    3. HIV DNA transcription and translation
      1. Proviral DNA is transcribed into messenger RNA (mRNA)
      2. mRNA is translated into HIV viral proteins
    4. HIV Budding
      1. Single stranded RNA and viral protein enzymes are repackaged via part of host cells membrane
      2. Newly formed encapsulated virus leaves the cell
    5. Reactivation Propagation
      1. HIV proviral DNA is activated after a latent period of months to years
      2. Reactivation and propagation via HIV Budding results in progressive CD4+ T Cell destruction
  5. References
    1. Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL

III. Course: Natural History of HIV Disease

  1. Total duration from initial HIV Infection to AIDS
    1. No treatment: 10 years
    2. Early Antiretroviral therapy: May approach normal Life Expectancy
  2. Active immune response after infection: 2.1 months
  3. Primary infection usually asymptomatic
    1. Acute Retroviral Syndrome in 30-50%
  4. Initial infection with single Genotype
    1. Evolves into 15-20 distinct viral variants
  5. Virus gains access to CD4+ Cells via sequential binding
    1. CD4 receptor via sequential binding with CD4 receptor in combination with CCR5 or CXCR4 co-receptors
  6. Over time:
    1. CD4+ Cell numbers decrease
    2. Viral concentrations increases

V. Staging: General

  1. Stage 1: CD4 500 Cells/mm3 or more
  2. Stage 2: CD4 200 to 499 Cells/mm3
  3. Stage 3: CD4 <200 Cells/mm3 or AIDS-Defining Illness

VI. Staging: Early disease (CD4 Count > 500 cells)

  1. Presentation
    1. No symptoms
    2. May show mild Lymphadenopathy
  2. Management
    1. Early Antiretroviral therapy is recommended for all stages of HIV
    2. Previously, asymptomatic patients in this stage received no therapy
  3. Course over following 18-24 months
    1. Risk of occult infection or death: <5%
    2. Slow decline in CD4 Counts (40 to 80 cells/year)

VII. Staging: Intermediate Disease (CD4 Count 200 - 500 cells)

  1. HIV related disorders
    1. Thrush
    2. Pronounced Vaginal Candidiasis, Onychomycosis
    3. Recurrent Herpes Simplex Virus Infection
    4. Recurrent Varicella Zoster Virus Infection
    5. Pruritic Folliculitis
    6. Recurrent Bacterial Infections
    7. Mycobacterium tuberculosis
    8. Anogenital ulcers or warts
  2. Complications
    1. Pneumocystis carinii Pneumonia
      1. Atypical in this stage
    2. Kaposi's Sarcoma
    3. Non-Hodgkin's Lymphoma
  3. Management
    1. Antiretroviral therapy is continued from prior stages
  4. Course (Untreated) over following 18-24 months
    1. Risk of occult infection or death: 20-30%
    2. Treatment reduces risk by 2-3 fold

VIII. Staging: AIDS Late Symptomatic Disease (CD4 50-200 Cells)

  1. Complications
    1. Development of Occult Infections
  2. Management
    1. Pneumocystis jiroveci prophylaxis (when CD4 Count <200 cells/mm3)
    2. Toxoplasmosis prophylaxis when CD4 Count <100 cells/mm3
    3. Antiretroviral therapy continues
  3. Course (Untreated) over following 18-24 months
    1. Risk of occult infection or death: 70-80%

IX. Staging: Advanced Disease (CD4 Count < 50-100 cells)

  1. Complications
    1. Disseminated Mycobacterium Avium Complex
    2. Cryptococcal Meningitis
    3. Cytomegalovirus retinitis
    4. Cryptosporidiosis
    5. Disseminated Histoplasmosis
    6. Progressive Multifocal Leukoencephalopathy
    7. Primary CNS Lymphoma
    8. AIDS Dementia
  2. Routine Management
    1. Anti-Pneumocystis carinii prophylaxis
    2. Antiretroviral Management
    3. Anti-Mycobacterium Avium Complex prophylaxis
      1. Start at CD4 Count < 50 cells/mm3
    4. Screen for CMV Retinitis
      1. Ophthalmology exam every 6 months
  3. Course
    1. High likelihood of Occult Infection or death

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