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.
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.
Ongoing Study Commitments
Adverse events associated with the use of Intelence may include, but are not limited to, the following:
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.
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Lazzarin A, Campbell T, Clotet B, Johnson M, Katlama C, Moll A, Towner W, Trottier B, Peeters M, Vingerhoets J, de Smedt G, Baeten B, Beets G, Sinha R, Woodfall B; DUET-2 study group Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet 2007 Jul 7;370(9581):39-48
Madruga JV, Cahn P, Grinsztejn B, Haubrich R, Lalezari J, Mills A, Pialoux G, Wilkin T, Peeters M, Vingerhoets J, de Smedt G, Leopold L, Trefiglio R, Woodfall B; DUET-1 study group Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet 2007 Jul 7;370(9581):29-38
TMC125-C223 Writing Group, Nadler JP, Berger DS, Blick G, Cimoch PJ, Cohen CJ, Greenberg RN, Hicks CB, Hoetelmans RM, Iveson KJ, Jayaweera DS, Mills AM, Peeters MP, Ruane PJ, Shalit P, Schrader SR, Smith SM, Steinhart CR, Thompson M, Vingerhoets JH, Voorspoels E, Ward D, Woodfall B Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis. AIDS (London, England) 2007 Mar 30;21(6):F1-10
Vingerhoets J, Azijn H, Fransen E, De Baere I, Smeulders L, Jochmans D, Andries K, Pauwels R, de Béthune MP TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. Journal of Virology 2005 Oct;79(20):12773-82
Andries K, Azijn H, Thielemans T, Ludovici D, Kukla M, Heeres J, Janssen P, De Corte B, Vingerhoets J, Pauwels R, de Béthune MP TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. Antimicrobial Agents and Chemotherapy 2004 Dec;48(12):4680-6
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For additional information regarding Intelence or HIV-1, please visit the Intelence web page.