Due to 91 lower plasma concentrations of tenofovir Non nucleoside Reverse

Due to 91 lower plasma concentrations of tenofovir

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Due to 91% lower plasma concentrations of tenofovir Non-nucleoside Reverse Transcriptase Inhibitors Drugs Efavirenz (sustiva) Rilpivirine (edurant) Etravirine (intelence) Doravirine (pifeltro) Pharmacology MOA: non-competitively inhibit RT Bind at hydrophobic pocket, distant from active site of RT Induces a conformational change in RT, alters the active site, limits its activity Do not require phosphorylation Class related properties Dosed QD or BID Administration requirements All undergo hepatic elimination Utilize CYP450 system for metabolism Low genetic barrier to resistance Toxicities No activity against host cell DNA polymerase Rash (class wide adverse event) Develops with first few weeks, resolves with continuation Rare causes of potentially fatal DRESS or SJ syndrome have been reported Fat accumulation after long-term use Efavirenz (sustiva) QD HS without food Increase BA with high fat meal results in increased SEs Moderate 3A4 inducer Weak to moderate CYP inhibitor Potential for teratogenicity
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CNS AE (drowsiness, insomnia, vivid dreams, and impaired concentration), rash Rilpivirine (edurant) QD w/ food 400 Cal of food and acidic environment Decrease BA with H2RAs, PPIs, etc Less effective if baseline HIV VL > 100,000 copies/mL or CD4 < 200 Resistance associated with cross resistance within class Best SE profile of available NNRTIs Rash, depression, HA, insomnia, transaminitis QTc prolongation Etravirine (intelence) BID with food Active against NNRTI-resistant strains Resistance associated with cross resistance within class 3A4 substrate and inducer 2C9 and 2C19 inhibitor Lower rates of rash and CNS SEs vs other NNRTIs Doravirine (Pifeltro, Destrigo) NNRTI Compared to other NNRTIs: Fewer drug interactions Can be taken w/ or w/o food More favorable lipid profile, lower incidence of rash, fewer CNS AEs vs efavirenz Non-inferior vs darunavir/ritonavir Pifeltro = doravirine Delstrigo = doravirine/lamivudine/tenofovir disoproxil fumarate Protease Inhibitors Drugs Lopinavir/Ritonavir (Kaletra) Atazanavir (Reyataz) Darunavir (Prezista) Ritonavir (Norvir) Pharmacology MOA: directly bind to HIV protease to prevent subsequent cleavage of polypeptides Visions are produced but are incomplete and non-infectious Class-related properties Multiple times daily dosing QD or BID with “boosting” Most inhibit 3A4 Substrates for P-gP efflux pump High genetic barrier to resistance Cobicistat (Tybost) question or on y ou if id
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Novel PK enhancer Potent and selective inhibitor of 3A4 Increases plasma concentrations of PIs and INSTIs No anti-HIV activity Exclusively used as enhancer Inhibits: 3A4, 2D6, PGP, BCRP, OATP1B1, OAT1B3 Modest, rapid increase in SCr, without affecting actual GFR PI-related toxicities
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  • Fall '19
  • Tetracycline, UTI, Ceftriaxone

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