Evaluating Once Daily Etravirine in Treatment-Naive Adults With HIV Infection

Summary

The main study is a single arm, open-label, prospective study to assess antiretroviral activity and tolerability of etravirine (TMC-125) 400 mg once daily, given with fixed-dose tenofovir/emtricitabine, in treatment-naïve HIV-1-infected men and women. There are also a genital secretions pharmacokinetic (PK) sub-study and a metabolic sub-study. The purpose of the genital secretions PK sub-study is to gain information about drug levels and HIV-1 RNA in genital secretions when subjects are taking etravirine. The purpose of the metabolic sub-study is to learn about the effects of etravirine on body composition, as well as lipid and glucose levels.

Timeline

Start

2009-09

Primary completion

2014-02

Completion

2014-05

Publications

• Background Gruzdev B, Rakhmanova A, Doubovskaya E, Yakovlev A, Peeters M, Rinehart A, de Dier K, Baede-Van Dijk P, Parys W, van 't Klooster G. A randomized, double-blind, placebo-controlled trial of TMC125 as 7-day monotherapy in antiretroviral naive, HIV-1 infected subjects. AIDS. 2003 Nov 21;17(17):2487-94. doi: 10.1097/00002030-200311210-00011.
• Background 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. 2007 Mar 30;21(6):F1-10. doi: 10.1097/QAD.0b013e32805e8776.
• Background Shikuma CM, Yang Y, Glesby MJ, Meyer WA 3rd, Tashima KT, Ribaudo HJ, Webb N, Bastow B, Kuritzkes DR, Gulick RM. Metabolic effects of protease inhibitor-sparing antiretroviral regimens given as initial treatment of HIV-1 Infection (AIDS Clinical Trials Group Study A5095). J Acquir Immune Defic Syndr. 2007 Apr 15;44(5):540-50. doi: 10.1097/QAI.0b013e318031d5a0.
• Background 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. doi: 10.1016/S0140-6736(07)61047-2.
• Background 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. doi: 10.1016/S0140-6736(07)61048-4.
• Background Ghosn J, Chaix ML, Peytavin G, Rey E, Bresson JL, Goujard C, Katlama C, Viard JP, Treluyer JM, Rouzioux C. Penetration of enfuvirtide, tenofovir, efavirenz, and protease inhibitors in the genital tract of HIV-1-infected men. AIDS. 2004 Sep 24;18(14):1958-61. doi: 10.1097/00002030-200409240-00014.
• Background Reddy YS, Gotzkowsky SK, Eron JJ, Kim JY, Fiske WD, Fiscus SA, Petch L, Cohen MS, Kashuba AD. Pharmacokinetic and pharmacodynamic investigation of efavirenz in the semen and blood of human immunodeficiency virus type 1-infected men. J Infect Dis. 2002 Nov 1;186(9):1339-43. doi: 10.1086/344311. Epub 2002 Oct 7.
• Background Taylor S, Reynolds H, Sabin CA, Drake SM, White DJ, Back DJ, Pillay D. Penetration of efavirenz into the male genital tract: drug concentrations and antiviral activity in semen and blood of HIV-1-infected men. AIDS. 2001 Oct 19;15(15):2051-3. doi: 10.1097/00002030-200110190-00022.
• Background van Praag RM, Repping S, de Vries JW, Lange JM, Hoetelmans RM, Prins JM. Pharmacokinetic profiles of nevirapine and indinavir in various fractions of seminal plasma. Antimicrob Agents Chemother. 2001 Oct;45(10):2902-7. doi: 10.1128/AAC.45.10.2902-2907.2001.
• Background Scholler-Gyure M, Kakuda TN, De Smedt G, Woodfall B, Lachaert R, Beets G, Peeters M, Hoetelmans RM. Pharmacokinetics of TMC125 in once- and twice- daily regimens in HIV-1-negative volunteers. Program and Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, 2007 [Abstract A-1427], Chicago IL.
• Background Lalezari J, et al. Pharmacokinetics of once-daily etravirine (ETR) without and with once-daily darunavir/ritonavir (DRV/r) in antiretroviral-naïve HIV-1 infected adults. 9th International Congress on Drug Therapy in HIV Infection 2008; abstract O413.
• Background 144-week data released on Gilead's study 934. AIDS Patient Care STDS. 2007 Aug;21(8):603-4. No abstract available.
• Floris-Moore MA, Mollan K, Wilkin AM, Johnson MA, Kashuba AD, Wohl DA, Patterson KB, Francis O, Kronk C, Eron JJ. Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. Antivir Ther. 2016;21(1):55-64. doi: 10.3851/IMP2982. Epub 2015 Aug 11.

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