HIV Flashcards
RTI
1) Nucleoside (NRTI)
Pyrimidine (Cytidine) Analogues
- Lamivudine
- Emtricitabine
Pyrimidine (Thymidine) Analogues
- Zidovudine
Purine (Guanosine) Analogues
- Abacavir
Purine (Adenosine) Analogues
- Tenofovir Disoproxil Fumarate
2) Non-Nucleoside (NNRTI)
- Efavirenz
- Rilpivirine
INSTI
Dolutegravir
Bictegravir
Raltegravir
Elvitegravir
Fusion Inhibitors
Enfuvirtide
PIs
Ritonavir
Lopinavir
Atazanavir
Darunavir
Fosamprenavir
PK Enhancers
Ritonavir (PI)
Cobicistat
CCR5 Antagonist
Maraviroc
ART Combinations
2 NRTI + 1 INSTI
- Tenofovir + Emtricitabine + Bictegravir
- Tenofovir + Emtricitabine + Dolutegravir
- Abacavir + Lamivudine + Dolutegravir
1 NRTI + 1 INSTI = Emtricitabine + Dolutegravir
- Not for HIV RNA > 500 000 copies/mL
- Not for HBV coinfection
- Not for those whose genotypic resistance testing of HIV or HBV testing are unavailable yet and you already want to start ART
NRTI advantages
ART Dual Backbone
Renal elimination
DDI not concerned
NRTI disadvantages
1) Mitochondrial toxicity (Rare, serious, More in Zidovudine)
- Lactic acidosis
- Hepatic Steatosis (Fat Infiltrate)
- Lipoatrophy (Fat loss)
2) Renal dose adjustments (Except abacavir)
NRTI ADRs (Specific to each)
Minimal toxicities
- Lamivudine – N/V/D
- Emtricitabine – N/D, hyperpigmentation
Tenofovir – N/V/D, Renal impairment, BMD decrease (TAF < TDF)
Abacavir – N/V/D, Hypersensitivity (HLA-B5701 – Rash, fever, malaise, fatigue, appetite loss, sore throat, cough, SOB, fatal ⇒ Discontinue, no rechallenge ⇒ Test for absence of HLA-B5701 before initiation), MI risk (Not used in CV risk patients)
Zidovudine – N/V/D, myopathy, bone marrow suppression (anemia, neutropenia)
INSTI Advantages
Good virologic effectiveness
Genetic barrier to resistance
Generally Well tolerated
INSTI disadvantages (Generally)
ADR:
- Weight gain
- N/D
- Headache
- Depression, suicidality (Rare, only in preexisting psychiatric)
DDI:
- Polyvalent cation coadministration
- CYP3A4 inducers/inhibitors
INSTI ADR (Specific)
Bictegravir / Dolutegravir – Inhibit SCr tubular secretion, no impact on GFR, resulting in increased SCr
Raltegravir – Pyrexia, Rhabdomyolysis (CK)
NNRTI Advantages
Long half life
Less metabolic toxicity than PIs (e.g. HLD, insulin resistance)
NNRTI Disadvantages
Genetic barrier to resistance is low
Cross resistance
Skin rash (Rilpivirine < Efavirenz)
CYP450 DDI
QTc prolongation
NNRTI ADRs
Efavirenz
- Rash
- HLD, LDL-C, TG
- Neuropsychiatric SE (Insomnia, depression, hallucination)
- Hepatotoxicity
Rilpivirine
- Depression
- Headache
NNRTI DDI
Efavirenz
- Substrate – CYP3A4
- Inducer – CYP2B6, CYP2C19
Rilpivirine
- Substrate – CYP3A4
- PPIs ⇒ Gastric pH increase ⇒ Reduced oral absorption
Protease Inhibitors Advantages
Genetic barrier to resistance
PI resistance is less common
Protease Inhibitors Disadvantages
- Metabolic complications (Dyslipidemia, Insulin resistance)
- GI side effects (N/V/D)
- Hepatotoxicity (esp HepB and HepC)
- CYP3A4 inhibitors and substrates ⇒ DDI
- Morphologic complication (Fat maldistribution, lipohypertrophy)
- Osteopenia / Osteoporosis
Protease Inhibitors ADRs
Ritonavir – Paresthesia (Numb extremities), taste perversion
Darunavir – Good GI tolerability, less lipid effects, Skin rash, SJS
Atazanavir – Good GI tolerability, less lipid effect, hyperbilirubinemia, QTc prolongation, skin rash
Protease Inhibitors DDI
Ritonavir – Potent CYP3A4, 2D6 inhibitor (Usually in combi with other PIs to boost levels)
Atazanavir – PPIs ⇒ Decrease absorption
Fusion Inhibitors Advantages
No DDI, Injection by SC BD
Fusion Inhibitors Disadvantages
Disadvantages – ADRs
Adverse Effects
- Injection site reaction (Erythema, induration, nodules, cyst, pruritus, ecchymosis
- Hypersensitivity, fever, rash, chills, BP drops (Rare)
- Bacterial pneumonia
CCR5 Antagonist Disadvantages and ADRs
Needs co-receptor tropism assay before initiation
Must be CCR5 predominant to use
Not to use if CXCR4 or dual/mixed tropism
CYP3A4 substrate
List of ADRs
- Abdominal pain
- Cough
- Dizziness
- Musculoskeletal symptoms
- Pyrexia
- Rash
- URTI
- Hepatotoxicity
- Orthostatic hypotension
