Integrase Inhibitors

Question 1

Integrase Inhibitors

INSTIs

Answer 1

Integrase strand transfer inhibitors

DTG- dolutegravir
RAL- raltegravir

Stribild- elvitegravir, cobicistat, emtricitabine, TDF
Genvoya- elvitegravir, cobicistat, emtricitabine, TAF
Triumeq- dolutegravir, abacavir, lamivudine

Anchor of preferred regimens for initial therapy
Excellent tolerability
Fewer drug interactions (except for elvitegravir)
One pill QD (except raltegravir)
Novel MOA means can be used in experienced patients

Only use is for HIV

Question 2

Integrase Inhibitors

(INSTIs) MOA

Answer 2

After RT creates a strand of viral DNA, integrase facilitates the transfer of the HIV DNA into the host cell’s genome
INSTIs prevent the viral DNA from becoming a part of the host cell enzyme (important step in HIV replication

Question 3

Integrase Inhibitors

(INSTIs) Adverse Effects

Answer 3

Musculoskeletal
Increases in creatine phosphokinase (raltegravir)
Most cases asymptomatic
Clinically evident myositis or rhabdomyolysis is rare

Renal
Fake renal dysfunction: cobicistat inhibits renal secretion of creatinine leading to increased levels of serum creatinine without a decline in GFR
But tenofovir can cause actual renal dysfunction

Question 4

Integrase Inhibitors

(INSTIs) Important Facts

Answer 4

Elvitegravir currently only available with cobicistat (and tenofovir, emtricitabine)

Raltegravir has few documented drug interactions
Dolutegravir has a few but closer to raltegravir

Have interaction with divalent and trivalent cations (like FQ and tetracyclines)- reduced absorption
Separate by 2 hours before or 6 hours after

Have relatively low genetic barrier to resistance; not as forgiving as PIs

Elvitegravir available in combo with TAF and TDF

Watch for interactions and cations: will reduce levels and cause resistance