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23 Cards in this Set
- Front
- Back
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Primary goal of Antiretroviral Therapy
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Reduce viral load
Preserve immune fxn Prevent transmission |
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Why is early treatment important
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Helps prevent transmission (96% reduction)
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Drug Types for Anti HIV
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RT Inhibitors
Protease Inhibitor integrase Fusion |
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Nucleoside RT Inhibitor (NRTI)
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Nucleoside (non phosphorylated) BETTER Penetration
MOA: 1) phosphorylation (RATE LIMITING and locks in cell) 2) interfere with RT by "poisoning" the nucleoside pool 3) prevent addition of natural nucleosides to growing chain |
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Tenofvir as a NRTI
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Actually a NT
has an arm for helping to get in the cell |
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NRTI Excretion
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Undergo Renal Excretion
EXCEPT: AZT -> glucoronidation ABC -> metabolized by ADH |
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Are there P450 Interactions with NRTIs
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NO
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Highly Active Anti Retroviral Therapy
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HAART --> ART
has significant toxicity associated with NRTI related mitochondrial toxicity SERIOUS Sd FX --> Hepatic Failure Steatosis (fatty change) Lactic Acidosis |
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Non Nucleoside RT Inhibitors (NNRTIs)
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Inhibit Viral RT by binding directly to RT Enzyme
Nevirapine Delavirdine Efavirenz (MOST POTENT) |
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Disadvantage of NNRTIs
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single mutation confers resistance to ALL NNRTIs
P450 drug rxn Rash Cross resistance Class adverse effects (increased transaminase levels, rash) |
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Advantages of NNRTIS
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Greater Half Life
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Protease Inhibitors
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1000x more selective for HIV protease than human protease
Prevents breakup of larger peptides into fxnal proteins |
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Fxn of Ritonavir
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in combo w/ 2° PI reduces metabolism by P450 and increases the bioavailability (inc. AUC, t1/2, Cmin/max)
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Advantages of PI
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Higher genetic barrier for resistance than NNRTIs and Integrase Inhibitors
PI resistance uncommon with RTV boosted PIs |
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Disadvantages of PI
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metabolic complications (dyslipidemia, insulin resistance, hepatotoxicity)
GI adverse rxns P450 inhibitors and substrates (potential for cross rxn) |
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Fusion Inhibitors (CCRr5 inhibitor)
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Bind surface proteins on CD4 cell surface or HIV cell surface --> prevent fusion
Maraviroc - cell Enfuvirtide - HIV |
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Maraviroc
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PO with F=23-33%
CCR5 Inhibitors (bind ccr5 on human cells) Binding prevents HIV-1 GP120 binding to CCR5 DOES NOT PREVENT CXCR4 tropid or dual tropic invasion |
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Disadvantages of Maraviroc
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hepatotoxicity from systemic allergic rexn
dizziness(postural hypotension) Risk of CV events |
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Integrase Inhibitor
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Integrase Strand Transfer Inhibitor (INSTI)
Blocks catalytic activity of HIV encoded integrase potent against HIV1/2 Raltegavir Elvitegravir |
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SLIDE 28
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a
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Slide 27
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a
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COBI
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Cobistat is a specific P450 inhibitor with no activity against HIV
Acts as a PK enhance of EVG (for once daily dosing) |
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Disadvantages of Elvitegravir
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Side FX
Nausea Diarrhea URT infxn and bronchitis Neck and joint pain UTI Many Drug drug interactions MUST BE USED WITH COBI |
