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Author: Amelia Virostko

1. Encounter

  1. Early risk groups: homosexual men, hemophiliacs, and IV drug users
  2. Sexual transmission or contaminated blood products
    1. Heterosexual transmission leading risk factor in developing countries

2. Entry

  1. Retrovirus coated by 2-layer lipid envelope
    1. gp120 binds CD4 and gp41 mediates membrane fusion
  2. p24 forms chief component of nucleocapsid
  3. Preferentially infects activated CD4 lymphocytes
  4. Follicular dendritic cells trap virus initially, but eventually degenerate after years of infection
  5. After viral uncoating, reverse transcriptase transcribes viral RNA into double-stranded DNA, which circularizes and integrates into the host genome using HIV integrase
  6. Synctytium-inducing variants are associated with greater cytopathicity and virulence resulting in more severe CD4 depletion through “innocent bystander” effect
  7. HIV requires usage of chemokine co-receptors CCR5 and CXCR4
    1. CCR5 heterozygous mutants have delayed progression to AIDS
    2. CCR5 homozygous mutants have decreased susceptibility to HIV infection
  8. Long-term nonprogressors have vigorous CD4 and broad-based cytotoxic responses
  9. Humoral immunity is not protective against HIV
    1. During late stage disease, patients often develop hypergammaglobulinemia

3. Spread

  1. Lymphoid tissue is a preferred and continuous site of viral replication

4. Multiplication

  1. 1010 virions produced and cleared in an infected person per day
  2. After an effective cellular response against HIV develops, a “set-point” of HIV RNA levels is attained which remains stable for years
  3. When the immune system is exhausted and CD4 replenishment cannot keep up with CD4 destruction, immunosuppression ensues
  4. During primary infection, high levels of viremia develop in days to weeks, followed by flu-like symptoms (e.g. fever, fatigue, pharyngitis, rash, lymphadenopathy)
    1. Genetic heterogeneity develops due to a lack of DNA proofreading mechanisms by the RNA virus
    2. High mutation rates and high levels of virus production can lead to viral resistance to antiretroviral therapy

5. Damage

  1. 50-70% of newly infected persons present with an acute mononucleosis-like syndrome 2-6 weeks after initial infection
  2. Continuous destruction of immune system leads to opportunistic infections and death

6. Outcome

  1. AIDS development generally occurs after 7-11 years of HIV infection
  2. 5-10% of patients remain asymptomatic and have normal CD4 counts and low HIV RNA levels for more than 10 years (long-term non-progressors)
  3. 10% of patients have a rapid clinical course to AIDS and die within 5 years
  4. Lifelong highly active antiretroviral therapy (HAART) helps suppress viral load
    1. Targets for therapy include HIV reverse transcriptase, HIV protease, HIV fusion, and HIV co-receptors