Antiretrovirals

Question 1

Integrase Strand Transfer Inhibitor’s (INSTIs)

Answer 1

MOA: bind integrase, inhibits final step in integration of viral DNA Into host DNA
SE:
Use: combo therapy approved for tx-experienced and tx-naive pt’s (few side-effects)

Question 2

Protease Inhibitors Drug Interactions and Resistance

Answer 2

Drug interactions: inhibition of CYP
CI: Rifampin and St. John’s Wort
Resistance: accumulation of mutations in protease gene

Question 3

Lamivudine

Answer 3

MOA: cytosine nucleoside analog (NRTI)
Resistance: high w/ single aa substitutions
SE: HA, dry 👄

Question 4

HIV Prophylaxis s/p Needle Stick Recommendation

Answer 4

Raltegravir + Tenofovir + Emtricitabine

Question 5

Enfuviritide

Answer 5

MOA: fusion inhibitor, structurally similar to gp41, binds gp41 subunit of viral envelop glycoprotein
Effect: prevent vision fusion w/ cell membrane
Use: tx-experienced adults w/ evidence of HIV replication
PK: parenteral only
SE: injection-related @ site, HS rxn

Question 6

Tenofovir

Answer 6

MOA: adenosine nucleotide analogue (NRTI)
PK: fixed-dose combination available (Tenofovir + Emtricitabine)
SE: N/V/D/gas
CI: monitor renal function, increases Didanosine concentrations and decrease Atazanavir concentrations

Question 7

Stavudine

Answer 7

MOA: thymidine nucleoside analog (NRTI), inhibitor of β and γ DNA polymerases
SE: peripheral neuropathy, lactic acidosis

Question 8

Maraviroc

Answer 8

MOA: binds specific/selectively to CCR5 blocking HIV entry
PK: metabolized by CYP3A4 (reduce dose when given w/ PIs)

Question 9

Didanosine

Answer 9

MOA: adenosine nucleoside analog (NRTI)
SE: pancreatitis (esp alcoholics and pt w/ hyperTG), peripheral neuropathy, diarrhea, liver dysfunction

Question 10

NRTIs

Answer 10

Competitive inhibition of RT
MOA: analog of ribosides (lack 3’OH), phosphorylated by enzymes and incorporated into viral DNA
Effect: chain termination
Spectrum: HIV-1 and HIV-2
Resistance: rapid if used alone, cross-resistance, mutation at codon 184 (lamivudine)
SE: neuropathy, myopathy, lipoatrophy and lactic acidosis, liver toxicity
Drug interactions: Didanosine levels increase w/ Tenofovir admin

Question 11

Ritonavir

Answer 11

Protease inhibitor
MOA: inhibit CYP3A4, increase plasma concentration of ARV allowing lower and less frequent dosing, improve tolerability
Use: combo w/ PIs (except Nelfinavir), NEVER used alone

Question 12

HIV Prophylactic Vaccines

Answer 12

S. pneumoniae, HAV, HBV, influenza

Question 13

Treatment-Naive Recommendations (PI-based)

Answer 13

Ritonavir-boosted Darunavir + Tenofovir + Emtricitabine

Question 14

NNRTIs Advantages/Disadvantages

Answer 14

Good: no effect on host blood-forming elements, lack cross-resistance w/ NRTIs
Bad: cross-resistance w/ NNRTIs, drug interactions, high incidence of HS rxn (rashes)

Question 15

Emtricitabine

Answer 15

Structurally similar to Lamivudine
MOA: cytosine nucleoside analog (NRTI)
SE: hyper-pigmentation of palms and soles

Question 16

Protease Inhibitors (PIs)

Answer 16

MOA: reversible inhibition of HIV aspartyl protease, prevents viral maturation
Effect: production of non-infectious varions
Spectrum: HIV-1 and HIV-2
PK: poor oral bioavailability, substrate for CYP-3A4 (most require low dose PK enhancer), substrate for P-gp pump
SE: buffalo hump (fat redistribution/accumulation), parasthesia, N/V/D, lipidemia, DM

Question 17

Elvitegravir

Answer 17

PK: metabolized by CYP3A4, may require PK enhancer (Cobicistat)
SE: well tolerated
Drug interactions: CYP interaction

Question 18

Raltegravir

Answer 18

PK: eliminated by glucoronidation via UGT1A1
SE: increases in CK
Drug interactions: Rifampin, Tipranavir and Efavirenz may decrease the concentration, PPIs may increase Raltegravir concentration

Question 19

Nevirapine

Answer 19

PK: excreted in urine
Metabolism: CYP-3A4 and CYP-2B6
SE: hepatotoxicity, rash, 2 wk titration @ 1/2 dose to reduce risk of reaction
CI: inducer of CYP-3A4, increases metabolism of PIs, contraceptives, Ketoconazole, Methadone, Metronidazole, Quinidine, Theophylline and Warfarin

Question 20

Ziduvodine

Answer 20

MOA: NRTI
Use: infant born to HIV infected mother (immediately after birth for 6 wks)
SE: dyslipidemia and insulin resistance, BM suppression
CI: toxicity potentially by co-admin of Probenecid, Acetaminophen, Lorazepam, Indomethnacin and Cimetidine; Statuvadine and Ribavirin activated by same pathways (might reduce active levels of Zidovudine)

Question 21

Rilpivirine

Answer 21

CI: pregnancy

Question 22

Vaccines CI in HIV pt w/ CD4 < 200

Answer 22

MMR, Varicella, Zoster (live vaccines)

Question 23

Treatment-Naive Recommendations (INSTI-based)

Answer 23

1. Raltegravir + Tenofovir + EMtricitabine

2. Dolutegravir + Tenofovir + Emtricitabine

Question 24

Dolutegravir

Answer 24

PK: eliminated by fglucoronidation via UGT1A1
SE: well tolerated
Drug interactions: CYP interactions (rarely)

Question 25

Cobicistat

Answer 25

MOA: inhibit CYP3A4, increase plasma concentration of ARV allowing lower and less frequent dosing, improve tolerability
Use: combo w/ INSTI Elvitegravir, and in combo w/ Darunavir and Atazanavir

Question 26

Abacavir

Answer 26

MOA: guanosine nucleoside analog (NRTI)
Resistance: develops slowly and requires several mutations
SE: GI sx’s, HA, dizziness, HS rxns
CI: pt w/ HLA-B*5701

Question 27

Efavirenz

Answer 27

SE: CNS (HA, loss of concentration, suicidal ideation), rash, increased blood lipids

Question 28

NNRTIs

Answer 28

Selective non competitive inhibition of HIV-1 RT
MOA: bind at distinct site, inhibit RNA and DNA dependent DNA polymerase
SE: skin rash (Steven Johnson), GI sx’s, CYP3A4 induction+, inhibition- or both