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47 Cards in this Set
- Front
- Back
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What type of virus is HIV?
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Retroviridae - enveloped RNA
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What is the replicative strategy of HIV?
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Reverse transcriptase makes copies of viral DNA from viral RNA, then a complementary strand is made giving viral dsDNA, then this is entered into host chromosomes and host cell RNA polymerases make mRNA from viral dsDNA
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Why does HIV mutate so much?
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Reverse transcriptase does not have proofreading capability, so replicates quickly but with errors that are not corrected
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What are some complications of the high mutation rate of HIV?
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HIV mutates at a rate of one nucleotide per day, which makes it hard to create a vaccine or use antivirals (resistance can develop quickly)
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What are the three key HIV genes?
Where do the HIV medications work? |
gag, pol, env
medications work at pol |
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What molecules are critical to HIV attachment to CD4 cells?
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CCR5
CXCR4 (on host cell) |
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Which HIV predominates in early infection?
In late infection? |
M-tropic which bind to CD4/CCR5 cells early in infection (macrophages, dendritic cells, some T cells)
T-tropic which binds to CD4/CXCR4 cells late in infection (to naive or helper T cells) |
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What is the sequence of HIV binding to a cell?
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gp120 on HIV binds to CD4, then conformational change, then gp120-CD4 binds to CCR5, then gp41 penetrates the membrane and the two membranes fuse and dump in RNA material
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What does integrase do?
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Splices HIV into the host genome
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What does protease do?
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Cleaves viral polyproteins during viral release from cell, rendering an infectious virion
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What are the divisions of HIV?
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2 types (HIV-1 and HIV-2)
HIV-1 has M, O, and N types Within M there are clades A-J |
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What is the most common type of HIV?
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HIV-1 M, clade B
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What parts of the body are clades C and E more likely to infect?
What parts of the world have this strain most? |
Vaginal mucosa, cervix, foreskin of penis (found in heterosexually-spread)
Asia and Africa |
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What are some differences between HIV-1 and HIV-2?
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HIV-2 is less infectious and has slower disease progression
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How is HIV-2 often treated?
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With protease inhibitors (have intrinsic resistance to NNRTIs)
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How do most males get HIV in the US? Most females?
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Males through MSM, females through high-risk heterosexual contact
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Is it easier to get HIV from male-->female or female-->male?
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male-->female (volume of fluid and amount of mucosa exposed)
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What is the method of transmission most likely to spread HIV to the recipient?
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Blood transfusion or organ transplant
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How many infections per 100 exposures will result in HIV from a needle stick?
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0.3
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How many days after exposure will an antibody assay be able to identify HIV infection?
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about 21 days (3-4 weeks usually)
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What diagnostic test is used to confirm an ELISA?
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Western blot
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What test cannot be used to diagnose HIV?
Why? |
CD4 count
It can be affected by a lot of different factors such as stress, steroids, illness) |
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What are the two factors important in disease progression?
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CD4 count
Viral load |
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What are some indications of HIV therapy?
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Nephropathy
Hep B CD4 <350 (recently changed to 500) Pregnancy Post-Exposure Prophylaxis AIDS-defining illness NOT VIRAL LOAD |
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Why is viral load not an indicator for HIV therapy?
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Cannot predict rate of CD4 cell count decline using HIV-1 RNA level
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How do NRTIs work?
What is the class side effect? |
Stops chain growth of viral DNA from viral RNA (which is done by RT)
Can cause lactic acidosis |
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What class is abacavir in? What is the side effect of it?
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NRTI
Causes hypersensitivity (rash in 2/3 along with fever, fatigue, GI distress, cough, pharyngitis) due to HLA-B*5701 |
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What is the most-commonly used NNRTI?
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Efavirenz
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What are two downsides to the use of efavirenz?
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Cannot give during pregnancy
Gives very vivid sexual dreams during the first month |
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What is the mechanism of action of NNRTIs?
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Bind directly to reverse transcriptase so it cannot add new nucleotides to viral DNA strand
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What are the class side effects of NNRTIs?
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Rash
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What is the biggest downfall to using NNRTIs?
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Class resistance - if lose resistance to one, lose it to all
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What are two advantages of using NNRTIs?
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Low pill burden and only take once daily - compliance is easy
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What are the class side effects of protease inhibitors?
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Drug interactions and dyslipidemia
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What is the main side effect of the protease inhibitor indinavir?
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Kidney stones (look for R flank pain or blood in urine as warning signs)
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What are the two most commonly used protease inhibitors?
Side effects? |
Fosamprenavir - parasthesias
Atazanavir - increased indirect bilirubin |
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What is the mechanism of action of fusion inhibitors?
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Prevents the virus from attaching to the CD4 cell
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In combination HIV medications what kinds of combinations are used?
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2 NRTIs and NNRTI
2 NRTIs and PI NRTI and NNRTI and PI Atripla common (efavirenz the NNRTI and FTC and TDF, the NRTIs) |
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What is the first type of resistance test done? What is next?
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Genotype, then phenotype or virtual phenotype
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What are the symptoms of acute retroviral syndrome?
What are people with this often diagnosed with? |
Nonspecific mild symptoms like fever, adenopathy, pharyngitis, maculopapular rash, myalgia
EBV Mononucleosis (except rash is often also found in mouth, genitals) |
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What tests should be used to confirm acute retroviral infection?
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HIV viral load (RNA, confirmed with serological testing)
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What are some potential complications of HIV treatment?
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Inflammatory syndrome/flare (CMV infection)
Worsening of previously-stable viral hepatitis Treat with NSAIDS, steroids, need to determine whether bad enough to discontinue HIV meds |
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What is the needlestick rule of 3?
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Chances of coming down with these infections due to a needlestick:
~HBV (30%) ~HCV (3%) ~HIV (0.3%) |
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When should PEP be considered, what does it involve?
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Percutaneous exposure is 0.3%, mucous membrane exposure is 0.09%, not a risk if exposure is through intact skin
Treat within a few hours and for 4 weeks - check HIV at baseline, 3mo, and 6mo |
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What is the mother-to-child transmission rate when triple drugs are being used (besides atripla)?
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1.2%
If viral load is over 1000c/mL, consider a C-section |
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What opportunistic infection has the broadest range of CD4 levels it will attack at?
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TB
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What is used to for primary prophylaxis for PCP when CD4 is under 200 and Toxoplasma when CD4 is under 100?
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Bactrim
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