Enfuvirtide
- MOA
- Pharmcokinetics
- Resistance
- AE
Synthetic 36-amino-acid peptide
Mechanism of action
- Binds to gp41 preventing the conformational and structural changes needed to allow fusion of the viral envelope with the host cell membrane
Pharmacokinetics
- Must be administered with subcutaneous injection (twice daily)
Resistance
- Mutations in gp41
Adverse effects
- Local injection site reactions, insomnia, HA, dizziness, insomnia
- No clinically relevant drug-drug interactions
maraviroc
Mechanism of action: Binds specifically and selectively to CCR5 to prevent viral entry into the host cell, should test for co-receptor tropism of HIV
Pharmacokinetics: Oral administration fecal excretion
Resistance: Mutations in the V3 loop of gp120, increase in CXCR4 receptor tropic virus which bypass CCR5 receptor to enter cell
Adverse effects: Generally, well tolerated, caution in ESRD
Systemic allergic reaction followed by hepatotoxicity has been reported
Discontinue maraviroc if this occurs
Dolutegravir
Preferred agent for treatment of treatment-naïve patients when combined:
tenofovir/emtricitabine
abacavir/lamivudine
Hypersensitivtiy (rash and systemic symptoms) have been reported
o Dolutegravir should be discontinued
Elvitegravir
Approved in 2012, only available as a part of a combination pill
Stribild® (elvitegravir, cobicistat, emtricitabine, and tenofovir)
Requires boosting to be efficacious
Combined with cobicistat
o Inhibits CYP3A4
Adverse effects
Few
Raltegravir
Pyrimidinone analog
A preferred option for treatment naïve persons beginning HAART
Recommended for use during pregnancy
Pharmacokinetics
Half-life is ~9 hours metabolized by UGT1A1
Adverse effects
Uncommon à diarrhea, n/v, fatigue, muscle aches, hypersensitivity reactions à discontinue
Boosted (inhibit metabolism) _______ is a recommended PI agent for use in pregnant women
Adverse effect: Most common - diarrhea and nausea
Skin rash in ~20% of patients
Indirect hyperbilirubinemia with overt jaundice (10%) d/t nonspecific inhibition of UGT1A1
Atazanavir
