• Half as many patients discontinued therapy due to adverse reactions with ISENTRESS + Truvada vs efavirenz + Truvada (3% vs 6%, respectively)
• The most commonly reported (≥2% in either treatment group) drug-related clinical adverse event (AE) of moderate to severe intensity^a in treatment-naïve patients receiving ISENTRESS and at a higher incidence compared with efavirenz was insomnia (4% vs 3%)
• STARTMRK was designed to evaluate the safety and efficacy of ISENTRESS 400 mg twice daily + Truvada vs efavirenz 600 mg at bedtime + Truvada in treatment-naïve, HIV-1-infected subjects
• The primary end point was noninferiority with respect to the percentage of patients with HIV-1 RNA
  <50 copies/mL at Week 48¹
  
  Click here to view study design

• Smaller mean change from baseline in total-C, TG, HDL-C, and LDL-C with ISENTRESS + Truvada vs efavirenz + Truvada through 48 weeks

• At baseline, serum lipid-lowering agents were used in 5% of patients receiving ISENTRESS and in 3% of patients receiving efavirenz

• ISENTRESS is used in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients
• This indication is based on analyses of plasma HIV-1 RNA levels up through 48 weeks in 3 double-blind controlled studies of ISENTRESS. Two of these studies were conducted in clinically advanced, 3-class antiretroviral—nonnucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI)—treatment-experienced adults and 1 was conducted in treatment-naïve adults
• The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response
• The safety and efficacy of ISENTRESS have not been established in pediatric patients

• For the treatment of patients with HIV-1 infection, the dosage of ISENTRESS is 400 mg administered orally, twice daily with or without food. During coadministration with rifampin, the recommended dosage of ISENTRESS is 800 mg twice daily with or without food

• During the initial phase of treatment, patients responding to ARV therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jiroveci pneumonia, Mycobacterium tuberculosis, or reactivation of varicella zoster virus), which may necessitate further evaluation and treatment
• Coadministration of ISENTRESS with drugs that are strong inducers of uridine diphosphate glucuronosyltransferase (UGT) 1A1 may result in reduced plasma concentrations of raltegravir
• Rifampin, a strong inducer of UGT1A1, reduces plasma concentrations of ISENTRESS. Therefore, the dose of ISENTRESS should be increased during coadministration with rifampin
• The impact of other inducers of drug metabolizing enzymes, such as phenytoin and phenobarbital, on UGT1A1 is unknown
• In drug interaction studies, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of the following: hormonal contraceptives, methadone, lamivudine, tenofovir, etravirine
• Coadministration of ISENTRESS with drugs that inhibit UGT1A1 may increase plasma levels of raltegravir
• The most common adverse reactions of moderate to severe intensity^a (>2%) that occurred at a higher rate than the comparator were insomnia in treatment-naïve patients and headache, nausea, asthenia, and fatigue in treatment-experienced patients
• Creatine kinase elevations were observed in subjects who received ISENTRESS. Myopathy and rhabdomyolysis have been reported; however, the relationship of ISENTRESS to these events is not known. Use with caution in patients at increased risk of myopathy or rhabdomyolysis, such as patients receiving concomitant medications known to cause these conditions
• ISENTRESS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
• To monitor maternal-fetal outcomes of pregnant patients exposed to ISENTRESS, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263

• To evaluate the safety and efficacy of ISENTRESS 400 mg twice daily + Truvada vs efavirenz 600 mg at bedtime + Truvada

• The primary end point (at Week 48) was noninferiority with respect to the percentage of patients with HIV-1 RNA <50 copies/mL
• Secondary end points (at Week 48) were:
  • Noninferiority with respect to the percentage of patients with HIV-1 RNA <400 copies/mL
  • Change from baseline in CD4 cell counts

• Randomized, double-blind, active-control study in treatment-naïve, HIV-1-infected adult patients
• Randomization was stratified by screening HIV-1 RNA levels (<50,000 or >50,000 copies/mL) and by hepatitis status
• N=563
• Aged ≥18 years
• Patients received either ISENTRESS 400 mg + Truvada or efavirenz 600 mg at bedtime + Truvada

References
1. Lennox JL, DeJesus E, Lazzarin A, et al; for the STARTMRK Investigators. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796–806.
2. Panel on Antiretroviral Guidelines for Adults and Adolescents; US Department of Health & Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents: November 3, 2008. www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed August 20, 2009.