HIV Pharm Flashcards by Kara Albright

When on tenofovir, what test do you need to have and how often?

urinalysis q 6 months

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What test do you need when giving a patient abacavir?

HLA-B 5701 test

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What tests do you need when giving a patient CCR5 blocker (ex: maraviroc)?

tropism testing

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What is ART?

antiretroviral therapy

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What is the fxn of ART?

reduce HIV-related morbid/mort at ALL stages of infection

reduced HIV transmission

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How does ART work?

suppresses plasma RNA viremia–> delays or prevents mutations, improves CD4 numbers

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How does ART in HIV therapy decrease cardiovascular and end-organ damage?

decreases inflammation and immune activation thought to contribute to them

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Can eradication of HIV be achieved with antiretrovirals?

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What can occur with abrupt ART discontinuation?

rebound viremia
worsening immune fxn
increased morb/mort

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Describe current ARV regimens

for viral suppression: combo of 3 active drugs from more than 2 drug classes

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What are the predictors of virologic success in HIV tmt

low baseline viremia

high potency of ARV regimen

tolerability of regimen

convenience of regimen

excellect adherence

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How fast does viral load reduction occur with ART

12-24 weeks, viral load is below limits of assay detection

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What are targets of HIV therapy?

nucleoside reverse transcriptase -

non-nucleoside reverse transcriptase -

integrase strand transfer - (inhibits integration)

HIV fusion - (inhibits attachment and fusion)

CCR5 - (inhibits CD4 and chemokine receptors used for attachment)

protease - (inhibits maturation)

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What is the backbone of ART?

2 NRTIs that target different bases are combined

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How do NRTIs work?

enter cell and phosphorlyated

compete for base pairs in the growing viral DNA strand, leads to termination of DNA production from RNA (lack 3’OH)

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What ARV drug prevents infection of susceptible cells but DOES NOT eradicate virus from cells that are already infected?

NRTIs

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What base pair does the NRTI AZT (zidovudine) compete with?

thymidine

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What base pair does the NRTI emtricitabine compete with?

cytidine

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What base pair does the NRTI lamivudine compete with?

cytidine

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What base pair does the NRTI abacavir compete with?

Guanosine

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What base pair does the NRTI tenofovir compete with?

adenosine

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Describe selective toxicity of NRTIs

need to inhibit HIV reverse transcriptase without disrupting host cell DNA poly

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What NRTIs would you use to not disrupt mitochondrial DNA polymerase y (d/t drugs having low affinity for DNA poly y)?

emtricitabine

lamivudine

abacavir

tenofovir

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Describe toxicities a/q NRTIs

lactic acidosis syndrome (d/t mito tox)

peripheral neuropathy (d/t mito tox)

pancreatitis (d/t mito tox)

anemia

myopathy

*****risks much lower now d/t use of drugs that don’t affect mito (tenofovir, abacavir, lamivudine, emtricitabine)

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What are toxicities of AZT/zidovudine?

bone marrow suppression skeletal muscle myopathy hepatic steatosis

Which NRTI was the first ARV discovered, competes with thymidine and is the only NRTI available IV?

AZT (zidovudine)

Which NRTI competes with thymidine but is rarely used because of toxicities such as fat wasting (lipodystrophy)?

stavudine (d4T) also peripheral neuropathy, lactic acidosis, hepatic steatosis

Which NRTI competes with cytosine, terminates elongation of DNA, has a long intracellular half-life, low barrier to resistance, active againts HBV, co-formulated with tenofovir (superior combo), and is excreted unchanged in urine?

emtricitabine (FTC)

What are toxicities a/w emtricitabine (FTC)?

ONE OF THE LEAST TOXIC ARV prolonged use--> hyperpigmentation of palms and soles in AA

What NRTI mimics emtricitabine but can be used as dual treatment with doltegravir for treatment in naive patients with low HIV numbers in plasma?

lamivudine (3TC)

What NRTI is the only guanine analog, NOT effective against HBV, not a CYP substrate, half life of 21 hours and shouldn't be given to pt with HLA B 5701 genotype (-->fatal hypersensitivity)?

ABC (abacavir)

What are toxicities a/w ABC (abacavir)?

potentially fatal hypersensitivity syndrome d/t HLA B 5701 genotype avoid in pts with CAD d/t a/w hyperlipidemia

What drug is a nuleoTIDE RTI, competes with adenosine, is approved for HBV, has a long half-life so can do 1x day dosing and is unchanged in urine?

TDF (tenofovir disoproxil fumarate)

What toxicities are a/w TDF?

nephrotoxicity with acute tubular necrosis--> Fanconi syndrome decreased bone mineral density

What is didanosine?

adenosine analong that is toxic d/t mito effects

What drug is a nuleoTIDE RTI, competes with adenosine, is approved for HBV, has a long half-life so can do 1x day dosing, is unchanged in urine and is well tolerated?

tenofovir alafenamine (TAF) transported differently c/w TDF (low dose but high intracellular concentrations)

What NRTI combo is used and superior to other combos?

emtricitabine and tenofovir

Are emtricitabine and lamivudine combined?

NO because they are both cytosine analogs

Are TAF and TDF combined?

no, both prodrugs with active tenofovir

What NRTI combo is used in naive patients with HIV?

lamivudine combined with INSTI dolutegravir

What active agents are recommended for treatment in naive HIV patients?

integrase strand transfer inhibitors (INSTI)

What do all INSTI drugs end in?

-gravir

What INSTI prevents formation of covalent bonds between viral and host DNA, generally well tolerated and is excellent target (DNA of humans doesn't undergo excision/reintegration)?

raltegravir

What INSTI blocks chromosomal integration of viral DNA, can develop resistence (high genetic barrier though) and should be avoided in pregnancy d/t neural tube defects?

dolutegravir

What INSTI is metabolized by CYP3A4 and needs to be boosted?

elvitegravir (combined with cobicistat)

What INSTI has similar resistance c/w dolutegravir but is only available as fixed-dose single tablet?

bictegravir

What are second line ART active agents?

protease inhibitors --> prevent cleavage of polypeptide and subsequent maturation of virion

How do protease inhibitors work?

competitively inhibit virus aspartyl protease (homodimer) --> human protease are monomers so not affected prevent cleavage of HIV gag and pol precursors that are needed to make reverse transcriptase, protease and integrase (mature)

Do PIs penetrate CSF?

no, highly protein bound

How do PIs affect CYP3A4?

inhibit metabolism of other drugs --> ritonavir used to boost other agents with low dose *****all substrates for P-glycoprotein

What is unique about indinavir?

early PI no longer recommended, but unique d/t crystaluria/renal stones

What drug was the first PI but is no longer widely used d/t pill burden?

saquinavir

What PI is a sulfa drug and can cause rashes?

darunavir

What PI causes unconjugated hyperbilirubinemia not associated with hepatitis?

atazanavir

What PI often works after failure of other PI-containing regiments and was boosted with ritonavir?

lopinavir --> now replaced with darunavir and azatanavir

What are the CYP3A4 inhibitors that boost PIs?

ritonavir cobicistat

What are third line active agents in ART?

Non-nucleoside reverse transcriptase inhibitors (NNRTI)

How do NNRTIs work?

only active against HIV 1 ---> HIV 2 resistant non-competitive antagonist to reverse transcriptase-->denatures it by binding to p66

What can happen with a single aa substitution in a pocket of NNRTIs?

resistance ex: single exposure to nevirapine causes resistance, must be combined with other drugs to prevent rapid resistance

What NNRTI was first approved for once daily dosing, is co-formulated with emtricitabine and tenofovir, should not be added to failing regimen and has CNS toxicity?

efavirenz was considered teratogenic but not anymore

What NNRTI is unique in that it still works after mutations that disrupt activity of other NNRTIs?

etravirine

What is the newest NNRTI that is best in class that has novel resistance mutations?

doravirine

What NNRTI is used with HIV-1 naive patients?

rilpivirine also not susceptible to malfunction with mutations

How do HIV fusion inhibitors work

add T20 peptides, prevent conformation change and fusion of virus with host

What drug is a 36aa peptide that inhibits viral infection via blocking fusion, not active against HIV-2, and must be given parenterally?

enfuvirtide (T-20) hella expensive and not used very often

What drug binds to CCR5 co-receptor and blocks entry into cells, NOT active against CXCR4 viruses, is a CYP3A4 substrate and generally well tolerated?

maraviroc not rec as initial therapy, seldom used

Maintaining less than 200 copies/mL of plasma HIV RNA...

prevents sexual transmission of HIV if first starting ART, wait 6 months or use other protection

What drug can cause neural tube defects?

dolutegravir

HIV Pharm Flashcards

(68 cards)