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What is the env gene for in HIV?

What does it code for?


Cleavage product of envelope glycoproteins--> gp120 and gp41

gp41 = fusion and entry

gp120 = attachment to host CD4+T cells


What is the function of the pol gene in HIV

pol—reverse transcriptase, aspartate protease, integrase.

integrates the virus into the host


What is the function of the gag (p24) in HIV?

gag = capsid protein


What are the three structual genes in HIV?

ƒ env (gp120 and gp41):: Formed from cleavage of gp160 to form envelope glycoproteins.
ƒ       gp120—attachment to host CD4+ T cell (docking). ƒ gp41—fusion and entry (transmembrane)


gag (p24)—capsid protein

pol—reverse transcriptase, aspartate protease, integrase.


Explain how HIV gets into host?

What does it bind to?

Who may have immunity to this virus?

Reverse transcriptase synthesizes dsDNA from genomic RNA; dsDNA integrates into host genome.
Virus binds CD4 as well as a coreceptor, either

CCR5 on macrophages (early infection) or CXCR4 on T cells (late infection).

Homozygous CCR5 mutation = immunity.

Heterozygous CCR5 mutation = slower course. 


What is the role of CCR5 in HIV

What about CXCR4

Virus binds CD4 as well as a coreceptor, either 

CCR5 on macrophages (early infection) or

CXCR4 on T cells (late infection). 


What do we use to screen for HIV? What characteritstics do we want this to have?

What do we confirm Dx with? What do we want this test to have?


Presumptive diagnosis made with ELISA (sensitive, high false-positive rate and low threshold, rule out test);

⊕ results are then confirmed with Western blot assay (specific, low false-positive rate and high threshold, rule in test). 


When does pt have AIDS?

Three different ways to determine this:

Viral load tests determine the amount of viral RNA in the plasma.

1. AIDS diagnosis ≤ 200 CD4+ cells/mm (normal: 500–1500 cells/mm3).

2. HIV-positive with AIDS-defining condition (e.g., Pneumocystis pneumonia)

3.  CD4+ percentage < 14%.  


When is an ELISA and Western Blot a less reliable test?

ELISA/Western blot tests look for antibodies to viral proteins; these tests often are falsely negative in the first 1–2 months of HIV infection and falsely positive initially in babies born to infected mothers (anti-gp120 crosses placenta). 


What pathogens are seen when viral count falls below 500

1. Scrapable white plaque, pseudohyphae on microscopy = thrush or Albicans

2. Unscrapable white plaque on lateral tongue= Hairy leukoplakia or EBV

3. Biopsy with neutrophilic inflammation= BAcillary angiomatosis  or Bartonella Henselae

4. Biopsy with lymphocytic inflammation = Kaposis sarcoma or HHV-8

5. Acid-fast oocysts in stool or Cryptosporidium (chronic watery diarrhea)

1. Scrapable white plaque, pseudohyphae on microscopy

2. Unscrapable white plaque on lateral tongue

3. Biopsy with neutrophilic inflammation

4. Biopsy with lymphocytic inflammation 

5. Acid-fast oocysts in stool 


What disease do we worry about with AIDS pts when counts fall under 200

1. MUltiple ring enhancing lesions on MRI

2. Dementia

3. Non enhancing areas of demyelination on MRI

4. Ground glass opacities on CXR

1. MUltiple ring enhancing lesions on MRI= brain abcess = Toxoplasmossis

2. Dementia = from HIV

3. Non enhancing areas of demyelination on MRI = PML from JC virus

4. Ground glass opacities on CXR = PNeumocytisis pneumo from PCP


Aids pts has horrible cough with pleuritic chest pain and hemoptysis. You get chest xray and see several cavitations and inflitrates. What is the pathogen responsible, what are his counts below?

Aspergillus fumigatus 

Below 100


AIDS pt has sensitivity to light, neck stiffness. The agent can be culture on Sabouraud agar and stains with indian ink  

What is the causitive agent?

What is his CD4 count?

What is a better way to dxs this?

Cryptococcus neoformans

CD4 under 100

Latex agglutination test detects THICK polysaccharide capsular YEAST and  “Soap bubble” lesions in brain. 



Pt with AIDS comes in with trouble seeing. You lineary ulcers on endoscopic exam and see white spots on endoscopy. 

What is the causitive agent?

What will you see on biopsy

CMV! can also cause retinitis, esophagitis, colitis, pneumonitis, encephalitis 

Biopsy reveals cells with intranuclear (owl eye) inclusion bodies 

seen with CD4 under 100


Single ring enhancing lesion in AIDs pt on MRI

Causitive agent?

EBV associated B-cell lymphoma (e.g., non-Hodgkin lymphoma, CNS lymphoma) 


Agent reponsible for low grade fevers, cough, hepatosplenomegaly and toung ulcer in AID pt

You see Oval yeast cells with macrophages that are CD4+

Histoplama capsulatum


Cell count is under 200

What are you at risk for?

What should you px?


prescribe TMP-SMX


Your CD4 is under 100

What are you at risk for?

What do you px?

PCP and toxoplasmosis

prescribe TMP-SMX


Your CD4 is under 50, what are you at risk for?

What should you prescribe?

Risk = Mycobacterium avium complx

Rx: Azithromycin or clarithrmoycin


Goals of HAART:


Highly active antiretroviral therapy (HAART): often initiated at the time of HIV diagnosis. Strongest indication for patients presenting with AIDS-defining illness, low CD4+ cell counts

(< 500 cells/mm3), or high viral load.

Regimen consists of 3 drugs to prevent resistance: 2 NRTIs and 1 of the following: NNRTI or protease inhibitor or integrase inhibitor 


What is the MOA of Protease inhibitors?

Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts.

Thus, protease inhibitors prevent maturation of new viruses. 


What drugs are protease inhibitors?

All protease inhibitors end in -navir. Navir (never) tease a protease. 

Atazanavir Darunavir Fosamprenavir Indinavir Lopinavir Ritonavir Saquinavir 


What is special about Ritonavir?

What kind of drug is it?

What' is MOA?

Ritonavir can “boost” other drug concentrations by inhibiting cytochrome P-450. 

Protease inhibitor


What is the side effect profile of Protease inhibitors?

What about specifically Indinavir?

Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy. 

Nephropathy, hematuria (indinavir). 


What drug should not be given with Protease inhibitors and why?

Rifampin (a potent CYP/UGT inducer)

contraindicated with protease inhibitors because it can decrease protease inhibitor concentration. 


What is the Mechanism of action of NRTIs?


Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3′ OH group) 


What are teh NRTIs?

What is their mechanism of action?

Abacavir (ABC) Didanosine (ddI) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4T) Tenofovir (TDF) Zidovudine (ZDV)

 Mechanism: competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3′ OH group) 


Which NRTI is different from the others?

Tenofovir is a nucleoTide; which the others are nucleosides and need to be phosphorylated to be active


What drug is given to women to prevent HIV transission to baby?

What's it's mechanism?

Zidovudine : NRTI

It competitively inhibits nucleotie binding to reverse transcriptase and terminates te DNA chain 


What is the side effect profile for NRTIs?

Bone marrow suppression (can be reversed with granulocyte colony-stimulating factor [G-CSF] and erythropoietin), peripheral neuropathy, lactic acidosis (nucleosides), anemia (ZDV), pancreatitis (didanosine). 


Bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides. 

NNRTIs: Delavirdine, Efavirenz, Nevirapine 


What is the mechanism of the following drugs?

Delaviridine, Efavirenz and Nevirapine?


Bind to reverse transcriptase site other then where NRTIS do and don't require phosphorylathion to be active or compete with nucleotides


What is the side effect profile with NNRTIs: Delviridine, Efavirenz, Nevirapine

Rash and hepatotoxicity are common to all NNRTIs. Vivid dreams and CNS symptoms are common with efavirenz. Delavirdine and efavirenz are contraindicated in pregnancy 


What is Raltegravir?

What is it's MOA?

Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase. 

Integrase inhibitor


What is the side effect of Raltegravir?

increases creatine kinase


Drug that Binds gp41, inhibiting viral entry. 



Drug that Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120.