human immunodeficiency virus (HIV)

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VASUpharm14
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human immunodeficiency virus (HIV)
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2014-06-23 20:22:24
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CH. 19 HIV
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  1. human deficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
    • HIV - RNA retro virus that attacks the immune system, mainly CD4+ T cells until possibly low enough to be susceptible to opportunistic infections
    • transmission - breast milk, blood, semen, vaginal secretions, sharing needles, unprotected intercourse, cuts/sores in vagina/penis/rectum/mouth
    • vertical transmission - mom to baby any time
    • CD4+ = immune function
    • HIV-1 RNA viral load = response to therapy
  2. HIV replication cycles and sites of action of antiretrovirals
    • 1. fusion of HIV cell to the host cell surface (Fusion inhibitor, CCR5 antagonist)
    • 2. HIV RNA, reverse transcriptase, integrase, viral proteins enter cell
    • 3. uncoating of viral core exposes the viral RNA which is converted to viral DNA by reverse transcriptase (NRTIs, NNRTIs)
    • 4. viral DNA is transported across the nucleus and integrates into host DNA (Integrase Strand Transfer Inhibitors)
    • 5. New viral RNA is used as genomic RNA and assemble viral proteins
    • 6. new viral RNA and proteins move to cell surface and a new, immature, HIV virus forms
    • 7. virus matures by protease releasing individual HIV proteins (PIs)
  3. lab parameters to measure in initial evaluation
    • 1. CD4+ count and HIV RNA viral load - prior to ART initiation or modification, 2-8 weeks post initiation, every 3-6 months thereafter
    • 2. drug resistance testing
    • 3. lipid panel, blood chemistry, CBC with differential - prior or modification and every 6-12 months thereafter
  4. crofelemer
    • Fulyzaq - for non-infectious diarrhea with HIV/AIDS on ART
    • MOA: inhibiting cyclic adenosine monophosphate (cAMP)-stimulated cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion channel and calcium activated chloride ion channels at teh enterocyte luminal membrane
    • SE: URTIs, bronchitis, cough, flatulence, increased bilirubin
    • Dose: 125 mg BID
  5. treatment overview
    • 1. NNRTI - NO cyp
    • 2. NRTI - A LOT OF CYP
    • 3. PI - A LOT OF CYP
  6. preferred initial combination regimens for Naive
    • 1. NNRTI-based: -
    • -efavirenz/tenofovir (RENAL)/emtricitabine
    • 2. PI-based: - 
    • -atazanavir (NO >20 mg omeprazole) + ritonavir + tenofovir (RENAL)/emtricitabine
    • -darunavir + ritonavir + tenofovir (RENAL)/emtricitabine
    • 3. INSTI-based: -
    • -raltegravir + tenofavir (RENAL)/emtricitabine
    • -elvitegravir/cobicistat/tenofovir (RENAL)/emtricitabine -- ONLY CRCL ≤70 ml/min
    • -dolutegravir + abacavir/lamivudine
    • -dolutegravir + tenofovir (RENAL)/emtricitabine
  7. preferred regimen for PREGGO
    • 1. PI-based: -
    • -lopinavir/ritonavir (BID always) + zidovudine/lamivudine
    • -atazanavir + ritonavir + zidovudine/lamivudine
    • 2. NNRTI-based: -
    • - nevirapine + zidovudine/lamivudine
  8. alternative regimens
    • 1. NNRTI-based: -
    • -efavirenz + abacavir/lamivudine
    • -rilpivirine/tenofovir/emtricitabine
    • -rilpivirine + abacavir/lamivudine
    • 2. PI-based: -
    • -atazanavir + ritonavir + abacavir/lamivudine
    • -darunavir + ritonavir + abacavir/lamivudine
    • -fosamprenavir + ritonavir + either (abacavir/lamivudine or tenofovir/emtricitabine)
    • -lopinavir + ritonavir + either (abacavir/lamivudine or tenofovir/emtricitabine)
    • 3. INSTI-based: -
    • -raltegravir + abacavir/lamivudine
    • *abacavir - NOT positive for HLA-B*5701, rilpivirine - NO viral load >100,000, NO PPI
  9. nucleoside/tide reverse transcriptase inhibitors (NRTIs) - ZALES DT - abacavir
    • Ziagen, Epzicom (+lamivudine)
    • BBW: lactic acidosis, hepatomegaly with steatosis, hypersensitivity, HLA-B*5701
    • SE: n/v, h/a, INC LFTs
    • Notes: avoid ETOH, no renal issues
  10. nucleoside/tide reverse transcriptase inhibitors (NRTIs) - ZALES DT - didanosine
    • Videx - not preferred
    • BBW: lactic acidosis, hepatomegaly with steatosis, pancreatitis
    • CI: allopurinol, ribavirin
    • SE: peripheral neuropathy, diarrhea, INC LFTs, Eyes, insulin resistance/DM
    • Dose: EC on EMPTY stomach, RENAL CRCL <60 ml/min lower dose
    • Notes: avoid stavudine combo, oral solution stable 30 d in Fridge
  11. nucleoside/tide reverse transcriptase inhibitors (NRTIs) - ZALES DT - emtricitabine
    • Emtriva, Truvada (+tenofovir), Atripla (+efavirenz, tenofovir), Complera (+ tenofovir, rilpivirine), Stribild (+tenofovir, elvitegravir, cobicistat)
    • BBW: lactic acidosis, hepatomegaly with steatosis, Hep B
    • SE: hyper pigmentation in palms and soles, n/v/d, rash, INC CPK, INC LFTs
    • Dose: 200 mg Qday caps, one tab Qday for Truvada, Atripla (EMPTY stomach at bedtime), Complera (FOOD) and Stribild (FOOD)
    • Notes: AVOID lamivudine (Epivir - no benefit), RENAL <50 ml/min lower dose, MedGuide
  12. nucleoside/tide reverse transcriptase inhibitors (NRTIs) - ZALES DT - lamivudine
    • Epivir, Combivir (+zidovudine), Epzicom (+abacavir), Trizivir (+abacavir,zidovudine)
    • BBW: lactic acidosis, hepatomegaly, NOT Epivir-HBV (lower dose lamivudine), Hep B
    • Dose: 150 mg BID or 300 mg Qday, RENAL <50 ml/min lower dose
    • Notes: AVOID emtricitabine (Emtriva - no benefit)
  13. nucleoside/tide reverse transcriptase inhibitors (NRTIs) - ZALES DT - stavudine
    • Zerit - not preferred
    • BBW: lactic acidosis, hepatomegaly, pancreatitis
    • SE: INC LFTs, insulin resistance/DM, peripheral neuropathy
    • Notes: avoid didanosine combo, avoid zidovudine combo, 30 d in Fridge
  14. nucleoside/tide reverse transcriptase inhibitors (NRTIs) - ZALES DT - tenofovir
    • Viread, Truvada (+emtricitabine), Atripla (EMPTY stomach at bedtime - emtricitabine, efaviranz), Complera (FOOD +emtricitabine, rilpivirine), Stribild (FOOD +emtricitabine, elvitegravir, cobicistat)
    • BBW: lactic acidosis, hepatomegaly, Hep B
    • SE: fanconi syndrome, RENAL, osteomalacia, BONE, GI, INC LFTs
    • Dose: 300 mg Qday, <50 lower dose, one tab Qday for combos
    • Notes: avoid didanosine combo, mix powder with soft foods, supplement
  15. nucleoside/tide reverse transcriptase inhibitors (NRTIs) - ZALES DT - zidovudine
    • Retrovir - preggo preferred
    • BBW: lactic acidosis, hepatomegaly, hematologic toxicity (neutropenia and anemia), myopathy (long-term)
    • SE: nail hyper pigmentation, myopathy, lipoatrophy, INC LFTs, hyper lipidemia
    • Notes: avoid stavudine combo, erythropoetin for anemia, IV for labor (>400 viral load)
  16. non-nucleoside reverse transcriptase inhibitors (NNRTIs) - NERDE - delavirdine
    • Rescriptor - avoid if possible
    • CI: alprazolam, ergot alkaloids, midazolam, rifampin, triazolam
    • SE: rash, hepatotoxicity
    • Notes: TID dosing
  17. non-nucleoside reverse transcriptase inhibitors (NNRTIs) - NERDE - efavirenz
    • Sustiva, Atripla (+emtricitabine, tenofovir) 
    • CI: ergot alkaloids, midazolam, pimozide, triazolam, St. John's Wort
    • SE: rash, hepatotoxicity, CNS, psychiatric, hyper lipidemia
    • Dose: 600 mg Qday with EMPTY stomach at bedtime
    • Notes: preggo D, continue efavirenz if already on
  18. non-nucleoside reverse transcriptase inhibitors (NNRTIs) - NERDE - etravirine
    • Intelence - experienced 
    • SE: rash, hepatotoxicity, INC cholesterol, hyper BG, peripheral neuropathy
  19. non-nucleoside reverse transcriptase inhibitors (NNRTIs) - NERDE - nevirapine
    • Viramune, XR - avoid if possible
    • BBW: hepatotoxic, SKIN
    • CI: hepatic
    • SE: RASH, hepatotoxicity, GI, INC LFTs
    • Notes: 14 day lead-in period, NOT CD4+ >250 F, >400 M = hepatoxicity
  20. non-nucleoside reverse transcriptase inhibitors (NNRTIs) - NERDE - rilpivirine
    • Edurant, Complera (+emtricitabine, tenofovir)
    • CI: all PPIs, rifabutin, rifampin, dexamethasone, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, St. John's Wort
    • SE: rash, hepatotoxicity, CNS
    • Dose: 25 mg Qday WITH meal, 1 tab Complera WITH meal
    • Note: keep in original container, away from light
  21. protease inhibitors (PIs) - LANDFIRST - atazanavir
    • Reyataz
    • CI: alfuzosin, amiodarone, cisapride, ergot derivatives, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, sildenafil, simvastatin, st. john's wort, triazolam, voriconazole 
    • SE: hyper BG, fat maldistrib, hyper lipids, hep, immune reconstitution syndrome, PR interval prolongation, "bananavir", nephrolithiasis (water), cholethiasis
    • Dose: 300 mg + 100 mg ritonavir Qday, WITH food + water
    • Notes: separate acid-suppressive drugs
  22. protease inhibitors (PIs) - LANDFIRST - darunavir
    • Prezista
    • CI: alfuzosin, amiodarone, cisapride, ergot derivatives, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, sildenafil, simvastatin, st. john's wort, triazolam, voriconazole 
    • SE: hyper BG, fat maldistrib, hyper lipids, hep, immune reconstitution syndrome, nausea, RASH
    • Warnings: sulfa allergy
    • Dose: 800 mg + 100 mg ritonavir Qday
    • Note: WITH food, swallow whole
  23. protease inhibitors (PIs) - LANDFIRST - fosamprenavir
    • Lexiva
    • CI: alfuzosin, amiodarone, cisapride, ergot derivatives, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, sildenafil, simvastatin, st. john's wort, triazolam, voriconazole 
    • SE: hyper BG, fat maldistrib, hyper lipids, hep, immune reconstitution syndrome, n/v/d, rash, nephrolithiasis (AFI)
    • Warning: sulfa allergy
    • Notes: NO food with oral suspension
  24. protease inhibitors (PIs) - LANDFIRST - indinavir
    • Crixivan - avoid if possible
    • CI: alfuzosin, amiodarone, cisapride, ergot derivatives, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, sildenafil, simvastatin, st. john's wort, triazolam, voriconazole 
    • SE: hyper BG, fat maldistrib, hyper lipids, hep, immune reconstitution syndrome, nausea, nephrolithiasis (water), indirect hyper bilirubinemia
    • Notes: WITH food+water, in original container with desiccant (prevent moisture)
  25. protease inhibitors (PIs) - LANDFIRST - nelfinavir
    • Viracept - avoid if possible
    • CI: alfuzosin, amiodarone, cisapride, ergot derivatives, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, sildenafil, simvastatin, st. john's wort, triazolam, voriconazole 
    • SE: hyper BG, fat maldistrib, hyper lipids, hep, immune reconstitution syndrome, diarrhea, rash
    • Notes: WITH food, NO ritonavir boost
  26. protease inhibitors (PIs) - LANDFIRST - ritonavir
    • Norvir
    • BBW: DI with antiarrhythmics, ergot alkaloids, sedatives/hypnotics
    • CI: alfuzosin, amiodarone, cisapride, ergot derivatives, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, sildenafil, simvastatin, st. john's wort, triazolam, voriconazole 
    • SE: hyper BG, fat maldistrib, hyper lipids, hep, immune reconstitution syndrome, n/v/d, paresthesias, asthenia, altered taste, PR prolongation
    • Dose: 100-400 mg/d - booster dose, WITH food
    • Notes: capsules 30 d RT (fridge it), tablets RT, solution RT - 43% ETOH
  27. protease inhibitors (PIs) - LANDFIRST - lopinavir + ritonavir
    • Kaletra
    • CI: alfuzosin, amiodarone, cisapride, ergot derivatives, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, sildenafil, simvastatin, st. john's wort, triazolam, voriconazole 
    • SE: hyper BG, fat maldistrib, hyper lipids, hep, immune reconstitution syndrome, n/v/d, pancreatitis, asthenia, abdominal pain, prolongation of PR AND QT interval
    • Dose: 800 mg lopinavir/200 mg ritonavir Qday or 400/100 mg BID, oral soln WITH food, solution FRIDGE
    • Notes: avoid once daily with carbamazepine, phenytoin, phenobarbital, preggos (inducers)
  28. protease inhibitors (PIs) - LANDFIRST - saquinavir
    • Invirase - avoid if possible
    • CI: alfuzosin, amiodarone, cisapride, ergot derivatives, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, sildenafil, simvastatin, st. john's wort, triazolam, voriconazole, hepatic, prolonged QT, refractory hypo kalemia/mag
    • SE: hyper BG, fat maldistrib, hyper lipids, hep, immune reconstitution syndrome, n/v/d, PR AND QT prolongation
    • Dose: within 2 hours of a full meal
    • Notes: AVOID QT >450 msec, ECG baseline
  29. protease inhibitors (PIs) - LANDFIRST - tipranavir
    • Aptivus - avoid if possible
    • BBW: combo ritonavir, hepatitis, intracranial hemorrhage
    • CI: alfuzosin, amiodarone, cisapride, ergot derivatives, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, sildenafil, simvastatin, st. john's wort, triazolam, voriconazole 
    • SE: hyper BG, fat maldistrib, hyper lipids, hep, immune reconstitution syndrome, diarrhea, rash, INC CPK, hepatotoxicity, intracranial hemorrhage (rare)
    • Notes: WITH food
  30. enfuvirtide
    • Fuzeon - experienced, salvage therapy
    • MOA: block attachment of HIV-1 virus with CD4 cells by blocking the confirmational change in gp41
    • SE: local injection, bacterial pneumonia
    • Dose: 90 mg SC BID
    • Notes: fridge and use in 24 hours, no DI
  31. maraviroc
    • Selzentry - experienced
    • MOA: bind to CCR5 co-receptor on CD4 cells to prevent conformational change for cell entry
    • BBW: hepatotoxicity
    • CI: RENAL CRCL <30 ml/min, 3A4 inhibitor/inducers
    • SE: upper respiratory tract infections, fever, rash, musculoskeletal, dizzy
    • Dose: 300 mg BID
    • Notes: must be CCR5-tropic, Pgp and 3A4 substrate - avoid st. john's wort
  32. integrase strand transfer inhibitors (INSTIs) - raltegravir
    • Isentress
    • SE: n/d, h/a, insomnia, pyrexia, CPK elevation, myopathy, rhabdo, rash
    • Monitor: CPK
    • Dose: 400 mg BID
  33. integrase strand transfer inhibitors (INSTIs) - dolutegravir
    • Tivicay
    • CI: dofetilide combo (tox)
    • SE: insomnia, h/a, diarrhea, rash, CPK elevation, INC LFTs - hep b/c
    • Notes: Separate antacids, laxatives, sucralfate, iron supplements, calcium supplements or buffered medication
  34. integrase strand transfer inhibitors (INSTIs) - elvitegravir + cobicistat + emtricitabine
    • Stribild
    • BBW: lactic acidosis, hepatomegaly with steatosis, Hep B
    • CI: alfuzosin, cisapride, ergot derivatives, lovastatin, midazolam, pimozide, rifampin, sildenafil, simvastatin, st. john's wort, triazolam
    • Warnings: RENAL and BONE
    • SE: proteinuria, n/d
    • Dose: 1 tablet daily WITH food
    • Notes: cobicistat booster like ritonavir, separate ANTACIDS only, raltegravir - UGT1A1 - watch with rifampin inducer, PPIs will increase levels raltegravir, cobicistat inhibitor 3A4, 2D6, Pgp. Elvitegravir - inducer 2C9
  35. Pre-exposure prophylaxis (PrEP)
    • prophy - emtricitabine/tenofovir (Truvada) 1 tab PO QDay
    • Criteria: -
    • 1. negative HIV
    • 2. CRCL ≥60 ml/min
    • 3. high risk for HIV
    • 4. screen Hep B, STDs
    • follow-up: every 2-3 months
    • -HIV test, 90 day supply each visit, preggo test, counseling
    • every 6 months - check Scr, CRCL, STDs test
  36. non occupational postexposure prophylaxis (nPEP)
    • ART prophy after nonoccupational exposure to HIV for 28 days - ≤ 72 hours since exposure 
    • 1. NNRTI-base: -
    • -efavirenz + (lamivudine or emtricitabine) + (zidovudine or tenofovir)
    • 2. PI-based: -
    • -lopinavir/ritonavir + (lamuvidine or emtricitabine) + zidovudine
  37. occupational postexposure prophylaxis (PEP)
    • ≤ 72 hours
    • raltegravir + tenofavir/emtricitabine (Truvada) for 4 weeks
  38. OTC HIV testing
    • OraQuick and Express HIV-1 Test System
    • antibody test - wait 3 months to avoid false negative
    • positive - "T" and "C"
  39. primary prophylaxis - opportunistic infections with HIV -pneumocystitis pneumonia (PCP)
    • Indication: CD4+ <200 or oropharyngeal candidiasis
    • regimen: TMP/SMX DS or SS Qday
    • D/C: CD4+ >200 for 3 months on ART
  40. primary prophylaxis - opportunistic infections with HIV - toxoplasma gondii
    • Indication: toxo IgG positive with CD4+ <100
    • regimen: TMP/SMX DS Qday
    • D/C: CD4+ >200 for 3 months on ART
  41. primary prophylaxis - opportunistic infections with HIV - mycobacterium avium complex (MAC)
    • Indication: CD4+ <50, rule out active disseminated MAC disease
    • regimen: azithromycin 1,200 mg weekly or clarithromycin 500 mg BID or azithromycin 600 mg BIW
    • D/C: CD4+ ≥100 for 3 months of ART

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