Info
🌱 來自: Huppert’s Notes
Antiretroviral Therapy (ART)🚧 施工中
Antiretroviral Therapy (ART)
Antiretroviral therapies are listed here, with select pros (+) and cons (-) indicated.
Nucleoside reverse transcriptase inhibitors (NRTI)
• Abacavir: (–) Risk hypersensitivity – must rule out HLA-B*5701 mutation first.
• Tenofovir: (–) 1. Renal toxicity: Decreases GFR → Risk of Fanconi’s syndrome. 2. Decreased bone density and risk of osteoporosis.
- TAF and TDF are two forms of tenofovir
• TAF has a lower risk of bone and renal toxicities
• TDF is associated with lower lipid levels
• Lamivudine: (+) Well-tolerated (–) Higher risk of resistance
• Emtricitabine: Very similar to lamivudine (think of them as being equivalent)
** Abacavir/lamivudine and tenofovir/emtricitabine are often paired.
Nonnucleoside reverse transcriptase inhibitors (NNRTI)
• Efavirenz: (–) Can cause bad dreams, worsening of underlying psychiatric disorders and suicidality
• Rilpivirine: (+) Better tolerated (–) Higher likelihood of resistance, requires food and gastric acid for absorption (can’t use with a PPI)
Protease inhibitors (PI)
• Darunavir: (+) Potent (i.e., high barrier to resistance) (–) Nausea, diarrhea, hyperlipidemia
• Atazanavir: Causes an indirect hyperbilirubinemia due to Gilbert’s. Not harmful; can be an indication of medication compliance.
- Boosters: PIs are often given with a booster (ritonavir of cobicistat) to improve potency and allow for less frequent and lower dosing. Both ritonavir and cobicistat are CYP450 inhibitors.
- Drug–drug interactions: PIs have many drug–drug interactions. When patients are taking a PI, it is worth discussing any dosing modifications needed when a new drug is started. Common drug classes with drug-drug interactions in the setting of PI use include:
• Acid reducers (PPIs, H2 blockers, antacids)
• Alpha-blockers (e.g., tamsulosin, prazosin, etc.)
• Anti-mycobacterial, macrolides, anti-fungals, and anti-malarials
• Anti-coagulants (including DOACs, dabigatran, and warfarin), anti-platelets
• Anti-convulsants
• Anti-depressants, anxiolytics, and anti-psychotics
• Anti-arrhythmics (e.g., amiodarone), beta-blockers
• HCV treatment
• Hormonal agents, including oral contraceptives
• Statins
• Opioids and medications used to treat opioid use disorder (e.g., buprenorphine, methadone)
Integrase inhibitors
• Elvitegravir: (–) Lower barrier to resistance than dolutegravir
• Dolutegravir: (+) Difficult to become resistance (–) Small bump in Cr, but no change in GFR
• Raltegravir: (–) BID dosing makes compliance more challenging
• Bictegravir: (+) High barrier to resistance, fewer side effects than dolutegravir (–) Small bump in Cr, similar to dolutegravir
Pharmacokinetic boosters
• Ritonavir: (+) Boosts protease inhibitors, increases trough so can be dosed daily (–) Nausea, diarrhea, hyperlipidemia
• Cobicistat: Similar to above (–) Decreases tubular secretion, so should not be used in patients with CKD
C-C chemokine receptor type 5 (CCR5) receptor antagonist
• Maraviroc: (–) Need to test tropism assay prior to use. Can cause hypersensitivity, hepatitis. Overall a less potent medication than others
Fusion inhibitors (not 1st line)
• Enfuvirtide: (–) Injectable, very common to get injection site reactions
Common starting ARV regimens
• Biktarvy = Bictegravir/tenofovir alafenamide/emtricitabine
• Descovy + Tivicay = Tenofovir alafenamide/emtricitabine + dolutegravir (TAF/FTC + DTG)
• Truvada + Tivicay = Tenofovir disoproxil fumarate/emtricitabine + dolutegravir (TDF/FTC + DTG)
• Raltegravir + (emtricitabine or lamivudine) + (TAF or TDF)
• Triumeq = Dolutegravir-abacavir-lamivudine (DTG/ABC/3TC)
- Only use in patients confirmed to be HLA-B*5701 negative given the adverse reaction associated with ABC in HLA-B*5701 positive individuals
• Dovato = Dolutegravir/lamivudine (DTG/3TC)
- This regimen cannot be used when: 1) HIV RNA > 500,000 copies/mL, 2) there is HBV co-infection, or 3) ART is going to be started before HIV resistance testing for reverse transcriptase or HBV testing are available