HIV Drugs Flashcards
Normal CD4 count? (range)
Copies of virus for the virus to be “suppressed”?
Normal: 800-1500 cells
Suppression: less than 50 copies/mL of the virus
How do NRTIs potentially cause lactic acidosis?
They block DNA-gamma, leading to dec. production of mitochondrial DNA W/o mitochondria the body depends on anaerobic synthesis, leading to lactic acidosis
What patients are contraindicated from using Abacavir/ why?
HLA-B 5701 patients because of a Hypersensitivity risk
Contraindication for Zidovudine?
Drug interactions?
Contraindicated in pts on Stavudine (antagonistic)
Interactions:
Ganciclovir– BM toxicity
Ribavirin– Antagonist
Contrimoxazole
MOA of NNRTIs
Resistance?
Noncompetively bind to RT and induce allosteric change, relaxing the enzyme function
You can develop resistance rapidly!!! (but it at least buys you time before using the PIs)
What is the only NNRTI you can give with Rifampin?
Efavirenz
Nevirapine vs Efavirenz
- Nevirapine is recommended as an alternative to Efavirenz in tx of naive women
- Nev. is severely hepatotoxic!
- Contraindications: women, CD4 < 250; men CD4 < 400
Ritonavir
- Against against what?
- Main AE?
- Indication?
- Similar to what drug?
- Active against HIV-1 and HIV-2
- AE = paresthesias (pins and needles)
- NOT a good ARV, but very useful for boosting the efficacy of other PIs (it’s a CYP inhibitor), allowing for reduction of dose/dose freq.
- Similar to Cobicistat
Statins can be useful in dealing w/ effects of metabolic syndrome from PIs, but you can’t use any that are CYP substrates.
Which Statins are OK to give with PIs? Which are not?
- OK: Pravastatin and Fluvastatin (no CYP met.)
- Not OK: Simvastatin, atorvastatin, lovastatin (CYP met.)
Trofile Assay purpose
Analyze potential resistance mechanisms and tell you which cell receptors (CCR5 or CXCR4) are prefered by the particular viral strain.
Who are CCR5 antagonist drugs particularly useful for?
Patients w/ viral suppression failure
What is our only injectable HIV med as of now?
Fusion inhibitor (enfuvirtide)
- Function of Integrase
- MOA of integrase inhibitors
- What mutations lead to resistance?
- Integrase allows viral DNA to integrate with the host cell DNA
- Integrase inhibitors block integrase fxn by binding Mg2+ required for strand transfer
- Mutations that alter orientation of Mg2+ ions can be resistant to INTIs
Name the integrase inhibitors.
How do they differ?
Raltegavir: standard INTI.
Elvitegravir: Shortest half-life; CYP substrate (but still approved!)
Dolutegravir: Longest half-life
Standard skeleton for combination of ART for tx of naive patients
- (2) NRTIs + (1) NNRTI
- (2) NRTIs + (1) PI
Preferred Dual- NRTI option
Tenofovir + Emtricitabine
What are the alternative dual-NRTI options?
Abacavir + lamivudine
Didanosine + lamivudine (or emtricitabine)
Zidovudine + Lamivudine
- Recommended NNRTI option?
- Alternate?
- Rec: Efavirenz
- Alt: Nevirapine (not in patients with hepatic impairment or too high of a CD4 count)
Preferred PI options and contraindications (if there are)
- Atazanavir + Ritonavir (contra. in patients who require high dose Proton pump inhibitors)
- Darunavir + Ritonavir
- Fosamprenavir + Ritonavir
Alternative PI options
- Unboosted atazanavir (except with tenofovir or didanosine/lamivudine)
- Fosamprenavir + RTV
- Saquinavir + ritonavir
Why wouldn’t you use these drugs together? Note any exceptions.
Atazanavir + indinavir
Potential hyperbilirubinemia
Why wouldn’t you use these drugs together? Note any exceptions.
Didanosine + Stavudine
High incidence of toxcity, potential serious lactic acidosis
Exception: when no other options are available
Why wouldn’t you use these drugs together? Note any exceptions.
Double NNRTI combo
Efavirenz and Nevirapine have more AEs together than separately. Both also reduce ETV.
Why wouldn’t you use this drug? Note any exceptions.
EFV in 1st trimester
Teratogenicity
Exception when no other option is available
