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General concepts regarding ARV treatment:
- - monotherapy (with NRTI) is not recommended.
- - HAART or combined therapy is standard.
- - treatment is based on whether pt is treatment-naieve or not.
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When to treat with ARVs.
- - all pts with an AIDs defining illness or CD4>350
- - pregnant pts, pts with HIV-associated nephropathy, or HBV coinfection (regardless of CD4 count)
- - CD4 between 350 and 500
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How good must adherance be with PIs to avoid resistance?
>95% adherance (increase likelihood by decreasing pill burden)
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Common AE of PIs and efavirenz
- metabolic and lipodystrophy complications
- - hyperlipidemia
- - abnormal fat distribution
- - hyperglycemia
- - cardivascular events
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Hypersensitivity and abacavir
- onset: 9 days to 6 weeks
- see: fever, rash, malaise
- screen pts for HLA-B*5701 before starting abacavir (if present, don't use)
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Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- ex. AZT, ddI, stavudine, abacavir
- NRTIs integrate into newly forming DNA and block propagation
- all are renally cleared except abacavir
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AZT (zidovudine)
- NRTI
- toxicities: bone marrow suppression, anemia, neutropenia
- do not give with ganciclovir
- may increase pigmentation of nails
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ddi (didanosine)
- NRTI
- acid labile, give with antacid to prevent drug breakdown
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Stavudine
- NRTI
- toxicities: lactic acidosis, ketoacidosis
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Abacavir
- NRTI
- Toxicities: hypersensitivity rxn (serious and potentially lethal, d/c immediately and do not attempt to use again)
- screen for HLA-B*5701
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Drug interactions and ARVs
Many, many drugs interact with ARVs, must always look up interactions.
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Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)
ex. nevirapine, delavirdine
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Nevirapine
- NNRTI
- lead-in dosing (start slow) to minimize incidence of rash.
- if rash develops do not increase dose until rash resolves
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Delavirdine
- NNRTI
- toxicities: rash - red with or w/o itching. will resolve. continue med through rash. d/c med if rash is accompanied by fever.
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Protease Inhibitors (PIs)
ex. Ritonavir, saquinavir, kaletra (combo drug)
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Ritonavir (Norvir)
- PI
- poorly tolerated
- used as a booster drug to increase levels and half-lives of other meds (p450 rxn)
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Kaletra (lopinavir/ritonavir)
- PI
- Ritonavir inhibits metabolism of lopinavir, resulting in higher levels of lopinavir
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Saquinavir
- PI
- not recommended to use w/o ritonavir to boost levels
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Entry Inhibitors
- Interfere with the process of viral binding to a cell, preventing infection
- only ARV given sub-Q
- very expensive (as are integrase inhibitors)
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Genotyping and HIV
- fairly common
- reveals genetic potential of most prevalent viral isolates in a patient
- predicts resistance, not sensitivity
- inexpensive, fast
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Phenotyping and HIV
- virus is cultured in various concentrations of ARVs
- sensitivity of pt's HIV strain is determined
- defines how a specific drug performs agains HIV strain
- expensive and relatively slow
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