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.

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.