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125 Cards in this Set
- Front
- Back
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Antiretroviral therapy, pregnancy, co-infxn with Hep B or C
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HIV infxn--early disease considerations
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Prophylaxis against reactivation of latent infxn, long term toxicity of antiretroviral tx
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HIV infxn--middle stage disease considerations
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Tx of opportunistic infxns/malignancy, supportive therapy
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HIV infxn--late/advanced stage disease consideration
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Viral replication begins when in infxn?
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Right from the start
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CD4 turnover is slow or rapid in infected cells?
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Rapid (t 1 1/2 = 3 days)
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Resistance develops faster or slower in early disease?
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Slower
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Immune fxn is better or worse early in disease?
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Better
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Five goals of antiretroviral therapy (ART)
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1)suppress viral replication
2)preserve immune response 3)delay immune dysfxn 4)improve quality of life 5)improve overall survival |
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Four things to consider before starting tx
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1)pt willingness to commit to complicated drug regimen
2)likelihood of adherence 3)degree of immune deficiency, CD4 count, viral load 4)likelihood of disease progression |
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What percentage adherence must a pt acheive for tx to be effective?
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90%-95%
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No tx, recommend tx, consider tx, optional tx: pt with CD4>350 and viral load <100,000
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No tx
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No tx, recommend tx, consider tx, optional tx: pt with CD4<350 and VL>100,000
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Recommend tx
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No tx, recommend tx, consider tx, optional tx: pt with CD4<200
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Recommend tx
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No tx, recommend tx, consider tx, optional tx: pt with opportunistic infxn, whatever the CD4 count
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Recommend tx
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No tx, recommend tx, consider tx, optional tx: pt with symptomatic HIV infxn
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Recommend tx
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No tx, recommend tx, consider tx, optional tx: pregnant women
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Recommend tx
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No tx, recommend tx, consider tx, optional tx: asymptomatic pt with CD4 between 201 and 350
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Consider tx
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Most docs would treat asymptomatic pt with CD4 between 201 and 350 if what?
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If pt is committed
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Lower CD4 counts predict what?
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More rapid progression to AIDS
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No tx, recommend tx, consider tx, optional tx: asymptomatic pt with CD4>350 and VL>100,000
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Consider tx
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Minimum recommendation for asymptomatic pt with CD4>350 and VL>100,000?
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Close monitoring for 3 mos
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Why might some docs treat asymptomatic pt with CD4>350 and VL>100,000?
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At risk for immune deterioration
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No tx, recommend tx, consider tx, optional tx: pt actively seroconverting
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Optional tx
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No tx, recommend tx, consider tx, optional tx: pt within 6 mos of seroconverting
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Optional tx
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All the Nucleoside Reverse Transcriptase Inhibitors (NRTIs) live on DAZZLES CT.
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1)Didanosine (ddI)
2)Abacavir (ABC) 3)Zidovudine (AZT) 4)Zalcitabine (ddC) 5)Lamivudine (3TC) 6)Emtricitabine (FTC) 7)Stavudine (d4T) 8)Combavir 9)Trizavir |
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Combavir is a combo of what two NRTIs?
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AZT + 3TC
(zidovudine + lamivudine) |
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Trizavir is a combo of what three NRTIs?
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ABC + AZT + 3TC
(abacavir + zidovudine + lamivudine) |
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What three side effect are associated with the NRTIs?
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Pancreatitis, neuropathy, lactic acidosis (rare but life-threatening)
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If a drug has "T" in its abbreviation, it's a *what* analog?
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Thymidine analog
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If a drug has "C" in its abbreviation, it's a *what* analog?
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Cytosine analog
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If a drug has "I" in its abbreviation, it's a *what* analog?
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Adenosine
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What is the only drug with "I" in its abbreviation?
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Didanosine (ddI)
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Which two drugs may cause hyperpigmentation of the palms/soles?
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Zidovudine (AZT) and Emtricitabine (FTC)
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Which drug is considered to be the safest NRTI?
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Lamivudine (3TC)
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Rash and anaphylaxis may be seen with what NRTI?
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Abacavir (ABC)
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Should you rechallenge with Abacavir (ABC)?
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No!
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Name the three Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
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Nevirapine (NVP), Delavirdine (rarely used) and Efavirenz (EFV)
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Nevirapine increases or decreases the AUC of protease inhibitors (PIs)?
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Decreases
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Delavirdine increases or decreases the AUC of PIs?
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Increases
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Serious hepatotoxicity is associated with early tx with which NNRTI?
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Nevirapine (NVP)
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Paradoxically, NVP's hepatotoxicity is associated with what?
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Good immune fxn (possibly something to do with BMI or cyp450 activity)
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EFV's long half life (40-55h) confers what benefit?
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One-a-day dosing
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Should you take EFV with or without food?
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Doesn't matter
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EFV can get into what important compartment?
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The brain-- it can cross the BBB
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EFV has what characteristic but not totally unpleasant side effect?
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Nightmares/vivid dreams for first few weeks
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EFV is good salvage for pts who fail on which two drugs?
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Delavirdine and NVP
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What is the only NucleoTide Reverse Transcriptase Inhibitor for HIV tx?
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Tenofovir (TNF)
(cidofovir- resistant CMV retinitis adefovir- HBV) |
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What are three good qualities of TNF?
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1)once-a-day dosing
2)it's well-tolerated 3)considered very safe |
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What quality of TNF gives it faster onset?
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It's monophosphorylated
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In general, protease inhibitors do what?
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They block proteolytic cleavage of the viral precursor gag-pol
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PIs are highly protein-bound, leading to what undesirable side effect?
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Poor bioavailability
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PIs interact with CYP450s, leading to what undesirable side effect?
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Many drug interactions
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PIs make a FAIR SNAK(L)
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1)Fosamprenavir (FOS)
2)Atazanavir (TAZ) 3)Indinavir (IND) 4)Ritonavir (RIT) 5)Saquinavir (SAQ) 6)Nelfinavir (NEL) 7)Amprenavir (AMP) 8)Kaletra (KAL) 9) Lopinavir |
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Kaletra is a combo of what two drugs?
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Lopinavir + ritonavir
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Kaletra may be used to salvage failures of what two PIs?
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saquinavir and nelfinavir
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This form of saquinavir (SAQ) has improved absorption
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Fortovase soft gel tab
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This saquinavir (SAQ) formulation is absorbed poorly
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Invirase
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When should saquinavir be taken in relation to meals?
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Within two hours of meals
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When should ritonavir (RIT) be taken in relation to meals?
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With meals
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This PI is used at low doses to block clearance of a 2nd PI.
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Ritonavir (it's called "ritonavir boosting")
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When should indinavir (IND)be taken in relation to meals?
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Should be taken on an empty stomach
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Two side effects of indinavir (vaguely kidney-related)
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Nephrolithiasis and insulin resistance
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When should nelfinavir (NEL)be taken in relation to meals?
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Take it with food.
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This side effect of nelfinavir (NEL) is predictable and easily controlled with fiber.
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Diarrhea
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What is the dietary concern with taking amprenavir (AMP)?
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Take it with or without food, just don't take it with fatty food.
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Amprenavir (AMP) may cause this derm side effect
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Rash
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Is it okay to rechallenge with amprenavir (AMP) once the rash is gone?
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Yes!
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What NRTI also causes a rash and SHOULDN'T be rechallenged?
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Abacavir (ABC)
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When do you take kaletra (KAL) in relation to meals?
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With meals
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Kaletra is a less-effective salvage for pts treated how?
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With multiple PIs
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What beneficial side effect is associated with atazanavir (TAZ)?
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Increased HDL level
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Atazanavir (TAZ) may not helpful in pts resistant to what?
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Other PIs
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Atazanavir may cause what inapparent side effect (hint: he doesn't look yellow to me!)
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Asymptomatic hyperbilirubinemia
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TRUE or FALSE: you should take fosamprenavir (FOS) on an empty stomach.
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False. You can take it with or without food.
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Fosamprenavir (FOS) is a prodrug of what other PI?
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Amprenavir
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Fosamprenavir (FOS) increases what more than what?
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Triglycerides more than cholesterol
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TRUE or FALSE: fusion inhibitors are good early tx for HIV infxn
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FALSE. Fusion inhibitors are last ditch therapy (hard to inject 2x/day for the rest of your life)
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FIs block HIV fusion by binding to what region of what?
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The HR1 region of Gp41
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FIs block what interaction needed for fusion?
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HR1-HR2
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What are four common side effects of FIs?
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1)injxn site irritation
2)bacterial pneumonia 3)increased AST and ALT 4)hypersensitivity |
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What is the starting NNRTI regimen for drug-naive pts?
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Efavirenz + (AZT or Tenofovir) + (3TC or Emtricitabine)
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Why might you replace efavirenz with nevirapine in the initial NNRTI regimen?
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You suspect pregnancy
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Why wouldn't you use delavirdine in place of efavirenz?
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Not potent enough
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What is the starting PI regimen for drug-naive pts?
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Kaletra + AZT + (3TC or emtricitabine)
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What four PIs **shouldn't** be used in the PI regimen?
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1)amprenavir
2)ritonavir alone 3)unboosted indinavir 4)unboosted saquinavir |
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This type of regimen should be used only when an NNRTI- or PI-based regimen cannot be used.
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Triple NRTI regimen
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What drugs make up the triple NRTI regimen?
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ABC + 3TC + AZT
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TRUE or FALSE: tx is recommended in ALL preggos, regardless of CD4 count or viral load.
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TRUE
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In women with a VL<1000, this drug can be used alone.
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AZT
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This drug has a long half life and is good for women in labor w/o any prior retroviral tx.
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Nevirapine
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3 other agents recommended for HIV (+) preggos (1 is a combo)
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Nelfinavir, saquinavir and AZT + 3TC
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You should NEVER use these 3 drugs in preggos (high teratogenicity)
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Efavirenz, ddC and delvirdine
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C section is recommended for what 2 types of women?
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Women on no Rx or only on AZT w/unknown VL
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But recent data suggests what about C-section?
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elective C-section may benefit all women.
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When should you start giving drugs to an HIV (+) pregnant woman?
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Week 14
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What if she's already taking Rx?
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Stop the meds, then restart at week 14
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When should you start treating the newborn?
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Within 6-12 hours of birth
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How long does it take HIV (+) people w/Hep C to develop cirrhosis?
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20% have it in 20 yrs (3x rate seen in HIV (-) )
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You treat for Hep C co-infxn when what 2 criteria are met?
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detectable plasma HCV RNA and liver biopsy showing bridging or portal fibrosis
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Tx works best in pts with what type of CD4 count?
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CD4>200
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What drug combo can you use to treat Hep C co-infxn?
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pegylated interferon + ribavin
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What should the viral load look like by 8 weeks of tx?
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should be a 1 log decline by 8 weeks
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By how much should T cell counts increase each year?
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100-150 cells (more in first three months)
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What accounts for initial rapid rise in CD4 cells?
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Redistribution of memory cells
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Repeated VL>400 copies after 24 wks of tx is defined as...
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incomplete response
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VL detectable after sustained period of suppression is called...
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rebound
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What 2 criteria make up "immunologic failure"?
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1)failure to increase CD4 count by 20-25 cells over baseline in first year of therapy
2)decrease in CD4 count below baseline |
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"Clinical progression" is defined as...
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occurrence or recurrence of an HIV-related event after 3 mos tx
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What are four causes of tx failure>
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1)adherence
2)toxicity 3)pharmacokintetics 4)resistance |
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Genotypic testing
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1)most commonly used
2)reverse transcriptase/protease genes are sequenced 3)mutations are polymorphisms vs. drug resistance mutations |
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phenotypic testing
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helps define inter-relationship between mutations (some are synergystic, some cancel each other out)
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Resistance testing is recommended when...
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pt fails successful regimen/has incomplete response
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Resistance testing is suggested for...
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pts seroconverting that you want to give drugs
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Resistance testing should be considered in...
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chronically infected pts initiating therapy
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Secondary prophylaxis protects against what?
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Recurring non-life-threatening infxns (thrush, HSV)
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Primary prophylaxis is used for what?
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Potentially lethal conditions (PCP, TB)
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Name 4 complications of long term antiviral tx?
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1)lactic acidosis
2)diabetes mellitus 3)fat redistribution 4)hyperlipidemia |
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How do NRTIs cause lactic acidosis?
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They have an affinity for DNA polymerase gamma that leads to mitochondrial dysfxn
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How do antivirals cause DM?
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beta cell destruction
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How do antivirals cause fat redistribution?
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Again, mito dysfxn
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This drug, used to battle CMV retinitis, comes as ocular implant and an oral form
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ganciclovir (oral form called valganciclovir)
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Name 3 drugs given IV for sight-threatening CMV retinitis
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ganciclovir, foscarnet, cidofovir
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Name 2 ways to treat non-sight-threatening CMV retinitis
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1)antiviral therapy only
2)oral valganciclovir |
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Generally, how do you treat active MAC infxn?
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a macrolide AB (clarithromycin) + ethambutol +/- rifabutin (may block PI absorption)
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What is the goal of therapy in end stage disease?
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control symptoms
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