ISENTRESS® (raltegravir 400 mg) film-coated tablets, for oral use; chewable tablets, for oral use; oral suspension and ISENTRESS® HD (raltegravir 600 mg) film-coated tablets, for oral use


In a clinical study of treatment-naïve adults with HIV-1, ISENTRESS + Truvada showed:

Long-Term Efficacy at 96 Weeks1

Difference in 96-week cumulative incidence of virologic, tolerability, and combined failure (97.5% CI)

ISENTRESS + Truvada (n=603)ATV/r + Truvada (n=605)DRV/r + Truvada (n=601)Difference between ISENTRESS + Truvada and ATV/r + Truvada : 3.4% (-0.7% to 7.4%)Difference between ATV/r + Truvada and DRV/r + Truvada : -2.2% (-6. 7% to 2.3%)Difference between ISENTRESS + Truvada and DRV/r + Truvada: 5.6% (1.3% to 9.9%)Difference between ISENTRESS + Truvada and ATV/r + Truvada : 12.7% (9.4% to 16.1 %)Difference between ATV/r + Truvada and DRV/r + Truvada : 9.2% (5.5% to 12.9%)Difference between ISENTRESS + Truvada and DRV/r + Truvada: 3.6% (1.4% to 5.8%)Difference between ISENTRESS + Truvada and ATV/r + Truvada : 14.9% (10.2% to 19.6%)Difference between ATV/r + Truvada and DRV/r + Truvada : 7.5% (2.3% to 12.7%)Difference between ISENTRESS + Truvada and DRV/r + Truvada: 7.5% (3.2% to 11.8%)9.0%12.6%14.9%0.9%13.9%4.7%8.6%24.1%16.6%Virologic FailureTolerability FailureCombined Failure

ACTG 5257 study design1


Patients were randomly assigned in a 1: 1: 1 ratio to receive 1 of 3 regimens, each with a fixed-dose combination of 300 mg of tenofovir disoproxil fumarate plus 200 mg of emtricitabine:

  • 400 mg of ISENTRESS twice daily (n=603) or,
  • 300 mg of atazanavir with 100 mg of ritonavir, both once daily (n=605) or,
  • 800 mg of darunavir with 100 mg of ritonavir, both once daily (n=601)


Randomized, open-label, active-controlled equivalence study. Patients were treatment-naïve adults with HIV-1 RNA >1000 copies/mL.

Primary Objective

Evaluate the regimen equivalence regarding virologic efficacy and tolerability over 96 weeks.

  • Protocol Defined Virologic Failure (PDVF)
  • HIV-1 RNA >1000 copies/mL from week 16 to before week 24 or >200 copies/mL at or after week 24.

Primary Tolerability End Point

Time from randomization to discontinuation of ISENTRESS, ATV/r, or DRV/r for toxicity.

Secondary Composite End Point

Earlier occurrence of virologic or tolerability failure.

Study Limitations

The trial was open-label.

Ritonavir was not provided, although co-pay reimbursements were provided where allowed by law.

Additional Study Design

  • 1809 patients; 42% non-Hispanic black, 34% non-Hispanic white, 22% Hispanic; 24% women
  • Approximately 31% of patients with HIV-1 RNA ≥100,000 copies/mL
  • 30% of patients with CD4 count <200 cells/µL
  • Key inclusion criteria: 10 or fewer days of prior ARV treatment and documented absence of genotypic resistance to reverse transcriptase inhibitors and protease inhibitors. lntegrase genotyping was not required because transmitted integrase resistance is rare.
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1. Lennox JL, Landovitz RJ, Ribaudo HJ, et al. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naïve volunteers infected with HIV-1: a randomized, controlled equivalence trial [published correction appears in Ann Intern Med. 2014 Nov 4;161(9):680]. Ann Intern Med. 2014;161(7):461-471.

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ISENTRESS and ISENTRESS HD are indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients.

Selected Safety Information

Severe, potentially life-threatening and fatal skin reactions have been reported. This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction and toxic epidermal necrolysis. Immediately discontinue treatment with ISENTRESS or ISENTRESS HD and other suspect agents if severe hypersensitivity, severe rash, or rash with systemic symptoms or liver aminotransferase elevations develops and monitor clinical status, including liver aminotransferases closely.

Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment.

ISENTRESS chewable tablets contain phenylalanine, a component of aspartame, which may be harmful to patients with phenylketonuria.

Coadministration of ISENTRESS or ISENTRESS HD with drugs that are strong inducers of uridine diphosphate glucuronosyltransferase (UGT) 1A1 may result in reduced plasma concentrations of raltegravir. Coadministration of ISENTRESS or ISENTRESS HD with drugs that inhibit UGT1A1 may increase plasma levels of raltegravir.

Coadministration of ISENTRESS or ISENTRESS HD and other drugs may alter the plasma concentration of raltegravir. The potential for drug-drug interactions must be considered prior to and during therapy. Coadministration or staggered administration of aluminum and/or magnesium-containing antacids and ISENTRESS or ISENTRESS HD is not recommended. Coadministration of ISENTRESS HD with calcium carbonate antacids, tipranavir/ritonavir, or etravirine is also not recommended.

Rifampin, a strong inducer of UGT1A1, reduces plasma concentrations of ISENTRESS and ISENTRESS HD. Therefore, the dose of ISENTRESS for adults should be increased to 800 mg twice daily during coadministration with rifampin. There are no data to guide coadministration of ISENTRESS with rifampin in patients below 18 years of age. Coadministration with rifampin is not recommended with ISENTRESS HD.

The impact of other strong inducers of drug metabolizing enzymes on raltegravir is unknown (e.g., Carbamazepine, Phenobarbital, and Phenytoin). Coadministration of ISENTRESS or ISENTRESS HD with other strong inducers is not recommended.

The most commonly reported (≥2%) drug-related clinical adverse reactions of moderate to severe intensity in treatment-naïve adult patients receiving ISENTRESS compared with efavirenz were headache (4% vs 5%), insomnia (4% vs 4%), nausea (3% vs 4%), dizziness (2% vs 6%), and fatigue (2% vs 3%), respectively. The most commonly reported (≥2%) clinical adverse reactions of all intensities (Mild, Moderate, and Severe) in treatment-naïve adult patients receiving ISENTRESS HD or ISENTRESS were abdominal pain, diarrhea, vomiting, and decreased appetite. Intensities were defined as follows: Mild (awareness of sign or symptom, but easily tolerated); Moderate (discomfort enough to cause interference with usual activity); or Severe (incapacitating with inability to work or do usual activity).

Grade 2–4 creatine kinase laboratory abnormalities were observed in subjects treated with ISENTRESS and ISENTRESS HD. Myopathy and rhabdomyolysis have been reported. Use with caution in patients at increased risk of myopathy or rhabdomyolysis, such as patients receiving concomitant medications known to cause these conditions and patients with a history of rhabdomyolysis, myopathy or increased serum creatine kinase.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ISENTRESS or ISENTRESS HD during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.

Women infected with HIV-1 should be instructed not to breastfeed if they are receiving ISENTRESS or ISENTRESS HD due to the potential for HIV transmission.

No dosage adjustment of ISENTRESS is necessary for patients with mild to moderate hepatic impairment. No hepatic impairment study has been conducted with ISENTRESS HD and therefore administration in patients with hepatic impairment is not recommended. The effect of severe hepatic impairment on the pharmacokinetics of raltegravir has not been studied.

Before prescribing ISENTRESS or ISENTRESS HD, please read the accompanying Prescribing Information. The Patient Information and Instructions for Use also are available.