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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
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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)
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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
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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
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treatment overview
- 1. NNRTI - NO cyp
- 2. NRTI - A LOT OF CYP
- 3. PI - A LOT OF CYP
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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
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preferred regimen for PREGGO
- 1. PI-based: -
- -lopinavir/ritonavir (BID always) + zidovudine/lamivudine
- -atazanavir + ritonavir + zidovudine/lamivudine
- 2. NNRTI-based: -
- - nevirapine + zidovudine/lamivudine
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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
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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
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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
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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
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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)
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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
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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
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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)
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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
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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
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non-nucleoside reverse transcriptase inhibitors (NNRTIs) - NERDE - etravirine
- Intelence - experienced
- SE: rash, hepatotoxicity, INC cholesterol, hyper BG, peripheral neuropathy
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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
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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
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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
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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
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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
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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)
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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
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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
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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
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occupational postexposure prophylaxis (PEP)
- ≤ 72 hours
- raltegravir + tenofavir/emtricitabine (Truvada) for 4 weeks
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OTC HIV testing
- OraQuick and Express HIV-1 Test System
- antibody test - wait 3 months to avoid false negative
- positive - "T" and "C"
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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
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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
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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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