Integrase Inhibitor

Antiviral Activity

Inhibits multiple isolates of HIV-1 with resistance to PIs, NNRTIs and NRTIs.

Mechanism of Action:

Inhibits HIV-1 integrase, thereby inhibiting the insertion of HIV DNA into the host cell genome.

Mechanism of Resistance:  

Mutations in the integrase gene that are associated with resistance to raltegravir include Q148, N155, and Y143.  Cross resistance is possible between raltegravir and investigational integrase inhibitors.


Administration of raltegravir after a high fat meal increases the area under the curve (AUC) by ~19%. FDA approved raltegravir use without regard to food. With twice daily dosing, steady-state is achieved by the second day of treatment. Raltegravir is 83% bound to human plasma protein. In animals, raltegravir crosses the placenta and is excreted in breast. Raltegravir is a substrate of P-gp in humans. Clearance of raltegravir in humans occurs via UGT1A1 mediated glucuronidation. The raltegravir terminal half-life is ~ 9 hours. No data are available regarding central nervous system distribution of raltegravir in humans, and animal data suggest limited penetration.

Adverse Effects:

The most common adverse events were headache, dizziness and nausea. Raltegravir does not appear to effect lipid measurements including triglycerides and low density lipoproteins.


In adults > 15 years of age, a dose of 400 mg twice daily is used. Raltegravir is not approved in children 15 years of age or younger.

Drug Interactions:

Rifampin and other strong inducers of UGT1A1 reduce plasma concentrations of raltegravir. Weak inducers of UGT1A1 may be used with the recommended dosage of raltegravir. Atazanavir, which is a strong inhibitor of UGT1A1, increases concentrations of raltegravir, however no dose adjustments are required for patients who are taking raltegravir with atazanavir.  Acid suppressing agents increase plasma concentrations of raltegravir, and caution should be used when using these agents concurrently.


Pregnancy Category C. There have been no well controlled studies in pregnant patients.

Brand Names:

 Isentress (Merck)