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What is the difference between "HIV-seropositive" and "AIDS"?

S+: if a pt has Ab to HIV (first way to detect infection)

AIDS: symptoms of opportunistic infections or Kaposi's sarcoma, their Th (CD4+) cells are <200/microL of blood


What is the virus that causes AIDS?



What is HIV-1's classification?

- A nontransforming retrovirus
- RNA virus that carries no oncogene


What is the origin of the AIDS virus?

Simian Immunodeficiency Virus (SIV)

Thought that HIV evolved from SIV in DRC


What is the approximate number of HIV cases in the US?

1.1 million


What is the approximate number of HIV cases in the world?

35 million


What is the rate of change in incidence?



Discuss the pathogenesis of AIDS. Include target cells types, mode of entry of virus, mode of exit, and latency vs productive infection

- After first exposure => high blood virus levels, peak at 6 weeks
- loss of CD4 cells in gut => increased gut permeability => systemic spread
- Ab peaks @ 9 wks, falls to almost 0 but at steady state
- DCs w/ HIV = Trojan horse, go to lymph nodes
- HIV gp120 bind to CD4 on Th cells => cause host cell CCR-5 binding as coreceptor
- CCR-5 binds => conf change of gp41 => exposes hydrophobic region that melts T cell membrane
- Th cell and virus fuse => vRNA and reverse transcriptase injected into cell => vDNA production
- W/ viral integrase, vDNA inserts at random break of host DNA => latent virus


What is the role of Tfh cells in persistence of HIV latency?

- They are able to suppress viral replication
- Can't eliminate the virus DNA from their nuclei


What is the role of Tfh cells in persistence of active HIV infection?

- If the Tfh cell w/ viral DNA is activated by its correct Ag => a clone of virus-producing cells
- Accompanied w/ or leads to dysregulation o f B cells


What are the types of infections seen in patients w/ AIDS?

1) Viral infection
2) Fungal infection
3) Protozoan infection
4) OIs of intracellular bacteria


What is the immunological basis for the spectrum of infection types seen in patients w/ AIDS?

- Virus targets T-cell mediated immunity
- More infections occur that require this


What are the possible reasons for which the total number of CD4 cells in patients w/ AIDS decline?

- When infected w/ HIV, you have to replace your CD4 cells OFTEN
- Simple exhaustion => decreased ability to produce more
- This is when CD4s decline... => opportunistic infections w/ a weak immune system


What are the reasons for apparent ineffectiveness of Ab in HIV infection?

- When virus is replicating => gp120/gp41 made early => inserted into plasma membrane of host
- Helps w/ fusion of infected cell to nearby uninfected CD4 cells
- Can spread w/o an extracellular phase
- Abs can't attack w/o extracellular presence

- Abs bind to virus but can't block attachment to/infection of Th cells
- Neutralizing epitopes on virus are shielded by carb --- if pt makes neutralizing Ab, virus mutates, escapes


Define "long term survivors" in HIV infection. Discuss

- Those who survived longer than other in the time before the first HIV drug, pre-1987
- Homozygous for 32-base pair deletion for CCR5 (chemokine, HIV coreceptor)
- 10% frequency in caucasians


Define "elite controllers" in HIV infection. Discuss

- Infected w/ HIV but didn't progress to AIDS
- 2/3 have HLA-B57 allele
- They just make effective CTL to HIV peptides presented at HLA-B57
- More HIV-specific CTL#s = better prognosis


Describe the laboratory diagnosis of AIDS

- Test for Ab to HIV
- Measured by ELISA (can have false+) => confirmed w/ Western blot analysis --- must bind to gp120/41 to be true positive

- Small amounts of RNA can be detected w/ PCR


What are the prospects of AIDS vaccine development?

Broad neutralizing Ab!!

- can block infection by almost all HIV strains/mutant forms
- Trying to find a vaccine that can produce that
- People (LTS) develop this Ab after having the disease for 20 years


What are the problems of AIDS vaccine development?

- Kind of like the flu vaccine
- Epitopes/virus is always changing => how do you make a vaccine with that?

As Cohen says: an HIV vaccine would neutralize today's virus but not tomorrow's


What are the three things that happen after HIV infects Tn cells?

HIV-infected T cells:

1) Die rapidly
2) Become persistent virus-producers
3) Enter latency


Why do HIV-infected T cells die rapidly?

- Viruses try to bud
- But it tears so many holes in membrane => cells dies


What is the standard antiretroviral therapy for patients w/ HIV?

- 2 NRTIs
- 1 drug from a different class (usually NNRTI)


What are two drugs that target reverse transcriptase?

1) Nucleosides (NRTI)
2) Non-nucleosides (NNRTI)


What are NRTIs?

- Competitive inhibitors of reverse transcriptase
- Chain terminators!


What are NNRTIs?

- Bind a hydrophobic pocket on reverse transcriptase => changes conformation => changes activity of catalytic site
- Escape common to these types of drugs


What is the target for protease inhibitors?

- The gag, pol, and env proteins
- These are made by cleaving a larger polyprotein using a viral protease


What is Enfuviritide?

- a fusion inhibitor
- binds to part og gp41 => can't change conformations => no cell entry/fusion


What is maraviroc?

- A CCR5 antagonist
- Blocks viral entry into CD4 cells
- Binds to transmembrane part of CCR5 => changes conformation of external receptor
- Can't bind to gp120


What is Raltegravir?

- Integrase inhibitor
- Used in pts w/ reverse transcriptase inhibitor-resistant strains of HIV