General Information

Intelence is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1). Reverse transcriptase a viral DNA polymerase enzyme that HIV needs to reproduce. Intelence blocks the enzymatic function of reverse transcriptase and prevents completion of synthesis of the double-stranded viral DNA ,thus preventing HIV from multiplying.

Intelence, in combination with other antiretroviral agents, is specifically indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents.

Intelence is supplied as a tablet designed for oral administration. The recommended initial dose of the drug is 200 mg (two 100 mg tablets) taken twice daily following a meal. If a patient is unable to swallow a tablet whole, it may be dispersed in a glass of water.

Mechanism of Action

Intelence is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1). Etravirine binds directly to reverse transcriptase and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. Etravirine does not inhibit the human DNA polymerases alpha, beta, and gamma.

Side Effects

Adverse events associated with the use of Intelence may include, but are not limited to, the following:

• Rash
• Diarrhea
• Nausea
• Fatigue
• Abdominal pain
• Peripheral neuropathy
• Hypertension
• Headache

Clinical Trial Results

FDA approval of Intelence was based on pooled 24-week results of two ongoing, identical phase III trials. These randomized, double-blinded, placebo-controlled studies were dubbed DUET-1 (TMC125-C206) and DUET-2 (TMC125-C216). The trials were designed to evaluate the safety and antiretroviral activity of Intelence in combination with a background regimen (BR) as compared to placebo in combination with a BR. Randomization was stratified by the intended use of enfuvirtide (ENF) in the BR, previous use of darunavir/ritonavir (DRV/rtv), and screening viral load. All study subjects received DRV/rtv as part of their BR, and at least two other investigator-selected antiretroviral drugs (N[t]RTIs with or without ENF. The endpoint was virologic response, defined as undetectable viral load (< 50 HIV-1 RNA copies/mL) at 24 weeks. At Week 24, 74% of Intellence-treated subjects achieved HIV-1 RNA < 400 copies/mL as compared to 51.5% of placebo-treated subjects. The mean decrease in plasma HIV-1 RNA from baseline to Week 24 was -2.37 log10 copies/mL for Intelence-treated subjects and -1.68 log10 copies/mL for placebo-treated subjects. The mean CD4+ cell count increase from baseline for Intelence-treated subjects was 81 cells/mm3 and 64 cells/mm3 for placebo-treated subjects. Of the population who either re-used or did not use ENF, 56.7% of Intelence-treated subjects and 32.7% of placebo-treated subjects achieved HIV-1 RNA < 50 copies/mL. Of the study population using ENF for the first time, 68.6% of Intelence-treated subjects and 61.3% of placebo-treated subjects achieved HIV-1 RNA < 50 copies/mL.