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20 Cards in this Set
- Front
- Back
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What is HAART?
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Highly-active anti-retroviral therapy
2 NRTIs + (NNRTI or PI+ritonavir) |
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What are the absolute indications for starting HAART?
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Symptoms and/or CD4 count <350
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What are the most common causes for failure of HAART?
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- Emergence of or baseline drug resistance
- Incomplete adherence |
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What are the recommendations for post-exposure prophylaxis?
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28 days of HAART, started within 72 hrs of exposure
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How do the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) work?
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- Incorporation into viral DNA chain causes chain termination
- Require intracellular phosphorylation to become active against HIV |
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What are the adverse effects of the NsRTIs (AZT, didanosine)?
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Nausea
Headache Lactic acidosis Anemia (AZT) Peripheral neuropathy Pancreatitis Lipodystrophy |
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What are the adverse effects of the NtRTIs (just TDF)?
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Nephrotoxicity
Fanconi’s syndrome (wasting) Bone mineralization disorders (like osteoporosis) |
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How do the non-nucleoside reverse transcriptase inhibitors (NNRTIs) work?
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- Noncompetitive inhibition of reverse transcriptase: binding to enzyme locks it in an inactive conformation
- Potent but subject to rapid emergence of resistance (only 1 point mutation necessary) - Active only against HIV-1 - CYP3A4 metabolism and potent induction or inhibition --> hard to predict DDIs |
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What are the adverse effects of the NNRTIs?
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Rash
Hepatotoxicity Neurocognitive impairment (efavirenz) Teratogenicity (efavirenz) DDIs (CYP3A4 induction/inhibition) Rapid emergence of resistance |
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How do the protease inhibitors (PIs) work?
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- Inhibit HIV protease by binding to its active site --> virions produced, but they are incomplete and non-infectious
- CYP3A4 metabolism and inhibition (varying degrees) - Major potential for DDIs |
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What are the adverse effects of the PIs?
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Major potential for DDIs (CYP3A4 inhibition)
Abdominal upset Diarrhea Long-term: dyslipidemia, lipodystrophy, atherosclerosis |
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Zidovudine (AZT)
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NRTI
- Specific adverse effect: anemia |
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Didanosine
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NRTI
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Emtricitabine (FTC)
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NRTI
- Has activity against HBV as well |
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Tenofovir disoproxil fumarate (TDF)
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NRTI
- Has activity against HBV as well - Adverse effects: nephrotoxicity, Fanconi’s syndrome (wasting), bone mineralization disorders (like osteoporosis) |
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Efavirenz
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NNRTI
- Most commonly-prescribed NNRTI - Specific adverse effects: neurocognitive impairment, teratogenicity |
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Ritonavir
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PI
- Potent inhibitor of CYP3A4 --> mainly used to “boost” levels of other PIs - Major DDIs |
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Enfuvirtide
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Fusion inhibitor
- Binds to gp41 to prevent viral fusion with host cell - Injectable only - Used as a salvage agent |
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Maraviroc
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CCR5 antagonist
- Binds to CCR5 on host CD4 cell - Effective only against R5 strains of HIV - Used as a salvage agent, but may be more effective in new infx |
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Raltegravir
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Integrase inhibitor
- Works synergistically with all antiretrovirals studied - Few side effects and DDIs - May soon be used as 3rd first-line tx option (2 NRTI + raltegravir) |
