Rilpivirine, a non-nucleoside reverse transcriptase inhibitor for the treatment of HIV infection

Current Opinion in Investigational Drugs

Volumn 9, Issue 8, 2008, Pages 899-912

  Ripamonti, D ^a   Maggiolo, F ^a  

^a OSPEDALI RIUNITI   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR PLUS LAMIVUDINE; ATORVASTATIN; DAPIVIRINE; DARUNAVIR; DARUNAVIR PLUS RITONAVIR; DELAVIRDINE; EFAVIRENZ; EFAVIRENZ PLUS EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; ETHAMBUTOL; ETRAVIRINE; FAMOTIDINE; KETOCONAZOLE; LAMIVUDINE PLUS ZIDOVUDINE; LOPINAVIR PLUS RITONAVIR; NANOCRYSTAL; NEVIRAPINE; NORETHISTERONE; PLACEBO; RALTEGRAVIR; RIFABUTIN; RILPIVIRINE; RITONAVIR; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; TENOFOVIR;

ABDOMINAL PAIN; ABNORMAL DREAMING; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL TRIAL; CONJUNCTIVITIS; DEPRESSION; DIARRHEA; DIZZINESS; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG EFFECT; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; ENTERITIS; FATIGUE; FOOD; FOOD DRUG INTERACTION; GASTROINTESTINAL DISEASE; GLUCOSE BLOOD LEVEL; HEADACHE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INJECTION SITE CONTUSION; INJECTION SITE ERYTHEMA; INJECTION SITE INDURATION; INJECTION SITE PAIN; INSOMNIA; LIPID BLOOD LEVEL; LIVER FUNCTION TEST; LIVER TOXICITY; MACULOPAPULAR RASH; MAXIMUM PLASMA CONCENTRATION; MENTAL DISEASE; MOUTH ULCER; NAUSEA; NIGHTMARE; NONHUMAN; PHARYNGITIS; RASH; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SLOW RELEASE FORMULATION; SOMNOLENCE; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; TIME TO MAXIMUM PLASMA CONCENTRATION; VERTIGO; VIRUS LOAD; VIRUS STRAIN;

ANIMALS; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; DRUG INTERACTIONS; HIV INFECTIONS; HIV REVERSE TRANSCRIPTASE; HUMANS; NITRILES; PATENTS AS TOPIC; PYRIMIDINES; REVERSE TRANSCRIPTASE INHIBITORS;

EID: 48349089312     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (52)

1. 578789 Roles of conformational and positional adaptability in structure-based design of TMC-125/R-165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. Das K, Clark AD Jr, Lewi PJ, Heeres J, De Jonge MR, Koymans LM, Vinkers HM, Daeyaert F, Ludovici DW, Kukla MJ, De Corte B et al J MED CHEM 2004 47 10 2550-2560
2. 587182 Data on investigational HIV compounds presented at CROI. Tibotec Pharmaceuticals PRESS RELEASE 2005 February 25
3. 587327 A series of diaryltriazines and diarylpyrimidines are highly potent non-nucleoside reverse transcriptase inhibitors with possible applications as microbicides. Van Herrewege Y, Vanham G, Michiels J, Fransen K, Kestens L, Andries K, Janssen P, Lewi P ANTIMICROB AGENTS CHEMOTHER 2004 48 10 3684-3689
4. 587331 In search of a novel anti-HIV drug: Multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl] -2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile (R-278474, rilpivirine). Janssen PAJ, Lewi PJ, Arnold E, Daeyaert F, de Jonge M, Heeres J, Koymans L, Vinkers M, Guillemont J, Pasquier E, Kukla M et al J MED CHEM 2005 48 6 1901-1909
5. 587336 TMC-278: Potent anti-HIV activity in antiretroviral therapy-naive patients. Goebel F, Yakovlev A, Pozniak A, Vinogradova E, Lewi P, Boogaerts G, Hoetelmans R, De Bethune MP, Peeters M, Woodfall B INT CONF RETROVIRUSES OPPORTUNISTIC INFECT 2005 12 Abs 160
6. 587338 TMC-278, a new potent NNRTI, with an increased barrier to resistance and good pharmacokinetic profile. De Bethune MP, Andries K, Azijn H, Guillemont J, Heeres J, Vingerhoets J, Lewi P, Lee E, Timmerman P, Williams P INT CONF RETROVIRUSES OPPORTUNISTIC INFECT 2005 12 Abs 556
7. 690629 Synthesis of novel diarylpyrimidine analogs and their antiviral activity against human immunodeficiency virus type 1. Guillemont J, Pasquier E, Palandjian P, Vernier D, Gaurrand S, Lewi PJ, Heeres J, de Jonge MR, Koymans LMH, Daeyaert FFD, Vinkers MH et al J MED CHEM 2005 48 6 2072-2079
8. 694209 Short-term antiviral activity of TMC-278 - a novel NNRTI - in treatment-naive HIV-1-infected subjects. Goebel F, Yakovlev A, Pozniak AL, Vinogradova E, Boogaerts G, Hoetelmans R, de Bethune MPP, Peeters M, Woodfall B AIDS 2006 20 13 1721-1726
9. 694229 The pharmacokinetic interaction between ketoconazole and TMC-278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI), in healthy HIV-negative subjects. van Heeswijk R, Hoetelmans R, Kestens D, Stevens M, Peeters M, Williams P, Woodfall B, Boven K INT AIDS CONF 2006 16 Abs TUPE0087
10. 769977 Tibotec's TMC-278 reduces viral load in phase IIb HIV trial. Tibotec Pharmaceuticals PRESS RELEASE 2007 March 01
11. 829866 The pharmacokinetic (PK) interaction between TMC-278, a next generation non-nucleoside reverse transcriptase inhibitor (NNRTI), and once daily darunavir/ritonavir (DRV/r) in HIV-negative volunteers. Van Heeswijk R, Hoetelmans RMW, Kestens D, Stevens M, Peeters M, Williams P, Woodfall B, Boven K ICAAC 2007 47 Abs H-1042
12. 830434 Spectroscopic studies of rilpivirine (TMC-278/R-278474) in complex with HIV-1 reverse transcriptase. Rashin AHL, Steege KE, Lee BJ, Das K, Bauman J, Frenkel YV, Arnold E, Castner EWJ FASEB J 2007 21 5 Abs 641.13
13. 830435 Synthesis of novel diarylpyrimidine analogs of TMC-278 and their antiviral activity against HIV-1 wild-type and mutant strains. Mordant C, Schmitt B, Pasquier E, Demestre C, Queguiner L, Masungi C, Peeters A, Smeulders L, Bettens E, Hertogs K, Heeres J et al EUR J MED CHEM 2007 42 5 567-579
14. 839699 NCT00540449: TMC-278-TiDP6-C209: A clinical trial in treatment naive HIV-1 patients comparing TMC278 to efavirenz in combination with tenofovir + emtricitabine. CLINICALTRIALS.GOV 2007 October 11
15. 840246 FDA approves new HIV drug. The Food and Drug Administration PRESS RELEASE 2007 October 16
16. 856597 Merck & Co's Isentress receives Canadian approval for HIV-1 infection. Canadian Government PRESS RELEASE 2007 November 30
17. 868820 FDA approves Tibotec's etravirine for HIV infection. Tibotec BVBA PRESS RELEASE 2008 January 18
18. 869035 FDA approves new HIV drug after priority review. The Food and Drug Administration PRESS RELEASE 2008 January 18
19. 877670 High-resolution structures of HIV-1 reverse transcriptase/TMC-278 complexes: Strategic flexibility explains potency against resistance mutations. Das K, Bauman JD, Clark ADJ, Frenkel YV, Lewi PJ, Shatkin AJ, Hughes SH, Arnold E PROC NATL ACAD SCI USA 2008 105 5 1466-1471
20. 908414 Effect of food and multiple dose pharmacokinetics of TMC-278 as an oral tablet formulation. Hoetelmans R, Kestens D, Marien K, Stevens M, Peeters M, Williams P, Bastiaanse L, Buffels R, Woodfall B INT WORKSHOP CLIN PHARMACOL HIV THER 2005 6 Abs 80
21. 908755 Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents - A Working Group of the Office of AIDS Research Advisory Council (OARAC) COMPANY PUBLICATION 2008 January 29 1-28
22. 908763 Merck & Co Inc Q1 2008 earnings call transcript. Merck & Co Inc COMPANY PRESENTATION 2008 April 21
23. 908771 Antiretroviral drug resistance testing in adults infected with human immunodeficiency virus type 1: 2003 recommendations of an International AIDS Society - USA panel. Hirsch MS, Brun-Vézinet F, Clotet B, Conway B, Kuritzkes DR, D'Aquila RT, Demeter LM, Hammer SM, Johnson VA, Loveday C, Mellors JW et al CLIN INFECT DIS 2003 37 1 113-128
24. 908772 Update of the drug resistance mutations in HIV-1: 2007. Johnson VA, Brun-Vézinet F, Clotet B, Günthard HF, Kuritzkes DR, Pillay D, Schapiro JM, Richman DD TOP HIV MED 2007 15 4 119-125
25. 908855 High resolution structures of HIV-1 RT from four RT-inhibitor complexes. Ren J, Esnouf R, Garman E, Somers D, Ross C, Kirby I, Keeling J, Darby G, Jones Y, Stuart D, Stammers D NAT STRUCT BIOL 1995 2 4 293-302
26. 910350 The pharmacokinetic (PK) interaction between famotidine and TMC-278, a next generation non-nucleoside reverse transcriptase inhibitor (NNRTI), in HIV-negative volunteers. Van Heeswijk R, Hoetelmans R, Kestens D, Stevens M, Peeters M, Williams P, Woodfall B, Boven K INT AIDS SOC CONF HIV PATHOGENESIS TREAT 2007 4 Abs TUPDB01
27. 910353 Pharmacokinetic interaction between the novel non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC-278 and tenofovir disoproxil fumarate (TDF) in healthy volunteers. Hoetelmans R, Kestens D, Stevens M, Peeters M, Williams P, Bastiaanse L, Buffels R, Woodfall B INT AIDS SOC CONF HIV PATHOGENESIS TREAT 2005 3 Abs WePe3.3C15
28. 910356 Neuropsychiatric events with TMC-278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI). Pozniak A, Steyn D, Grinsztejn B, Vinogradova E, Lupo S, Techasathit W, Vanveggel S, Peeters M, Goilav C, Williams P, Woodfall B et al INT AIDS SOC CONF HIV PATHOGENESIS TREAT 2007 4 Abs WEPEA105
29. 910358 The metabolic profile of TMC-278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI). Ruxrungtham K, Bellos N, Morales-Ramirez J, Timerman A, Madruga J, Katabira E, Vanveggel S, Peeters M, Stevens M, Williams P, Woodfall B et al INT AIDS SOC CONF HIV PATHOGENESIS TREAT 2007 4 Abs TUAB105
30. 910360 Pharmacokinetic interaction between TMC-278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI), and lopinavir/ritonavir (LPV/r) in healthy volunteers. Hoetelmans R, van Heeswijk R, Kestens D, El Malt M, Stevens M, Peeters M, Williams P, Buffels R EUR AIDS CLIN SOC 2005 10 Abs PE4.3/1
31. 912602 Concentration- and pH-dependent aggregation of hydrophobic drug molecules and relevance to oral bioavailability. Frenkel YV, Clark AD Jr, Das K, Wang YH, Lewi PJ, Janssen PA, Arnold E J MED CHEM 2005 48 6 1974-1983
32. 913165 Identification and prediction of promiscuous aggregating inhibitors among known drugs. Seidler J, McGovern SL, Doman TN, Shoichet BK J MED CHEM 2003 46 21 4477-4486
33. 913208 Long-acting TMC-278, a parenteral depot formulation delivering therapeutic NNRTI concentrations in preclinical and clinical settings. van't Klooster G, Verloes R, Baert L, van Velsen F, Bouche MP, Spittaels K, Leempoels J, Williams P, Kraus G, Wigerinck P INT CONF RETROVIRUSES OPPORTUNISTIC INFECT 2005 12 Abs 134
34. 913214 48-Week primary analysis of trial TMC-278-C204: TMC-278 demonstrates potent and sustained efficacy in ART-naive patients. Pozniak A, Morales-Ramirez J, Mohapi L, Santoscoy M, Chetchotisakd P, Hereygers M, Vanveggel S, Peeters M, Woodfall B, Boven K INT CONF RETROVIRUSES OPPORTUNISTIC INFECT 2007 14 Abs 144LB
35. 913220 Lower lipid levels in antiretroviral (ARV)-naive patients receiving the investigational NNRTI TMC-278 versus efavirenz (EFV). Pozniak A, Yazdanpanah Y, Shalit P, Vanveggel S, Peeters M, Stevens M, Williams P, Woodfall B, Boven K EUR AIDS CLIN SOC 2007 11 Abs P9.2/05
36. 913225 TMC-278, a next-generation NNRTI, demonstrates potent and sustained efficacy in antiretroviral (ARV)-naive patients: Week 48 primary analysis of study TMC-278-C204. Yeni P, Goebel F, Thompson M, Vanveggel S, Peeters M, Stevens M, Williams P, Woodfall B, Boven K EUR AIDS CLIN SOC 2007 11 Abs P7.2/07
37. 913227 The pharmacokinetic (PK) interaction between atorvastatin (AVS) TMC-278, a next generation non-nucleoside reverse transcriptase inhibitor (NNRTI), in HIV-negative volunteers. van Heeswijk RPG, Hoetelmans RMW, Aharchi F, Stevens M, Peeters M, Williams P, Woodfall B, Boven K EUR AIDS CLIN SOC 2007 11 Abs P4.3/04
38. 913819 Results of BENCHMRK-1, a phase III study evaluating the efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus. Cooper D, Gatell J, Rockstroh J, Katlama C, Yeni P, Lazzarin A, Chen J, Isaacs R, Teppler H, Nguyen B INT CONF RETROVIRUSES OPPORTUNISTIC INFECT 2007 14 Abs 105aLB
39. 913822 Results of BENCHMRK-2, a phase III study evaluating the efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus. Steigbigel R, Kumar P, Eron J, Schechter M, Markowitz M, Loufty M, Zhao J, Isaacs R, Nguyen B, Teppler H INT CONF RETROVIRUSES OPPORTUNISTIC INFECT 2007 14 Abs 105bLB
40. 914062 Clinical care options HIV - The clinical impact of next-generation NNRTIs: Recent research and practical treatment strategies (rilpivirine). Pozniak AL INTERNET SITE 2008 June 06
41. 914715 The effect of different types of food on bioavailability of TMC-278, an investigational NNRTI. Crauwels HM, van Heeswijk RPG, Bollen A, Stevens M, Buelens A, Boven K, Hoetelmans RMW INT WORKSHOP CLIN PHARMACOL HIV THER 2008 9 New Orleans Abs P32
42. 914826 Switch strategies in patients on effective HAART. Maggiolo F, Ripamonti D, Suter F J ANTIMICROB CHEMOTHER 2005 55 6 821-823
43. 914828 Efavirenz versus nevirapine in current clinical practice: A prospective, open-label observational study. Manfredi R, Calza L, Chiodo F J ACQUIR IMMUNE DEFIC SYNDR 2004 35 5 492-502
44. 914829 Transmission of drug-resistant HIV-1 in Europe remains limited to single classes. SPREAD programme AIDS 2008 22 5 625-635
45. 915152 Strategic flexibility of the non-nucleoside RT inhibitor TMC-278 explains its potency against drug-resistant mutants. Das K, Bauman JD, Baweja M, Clark AD Jr, Boyer PL, Shatkin AJ, Lewi PJ, Hughes SH, Arnold E ANTIVIR THER 2007 12 5 Suppl 1 Abs 31
46. 920103 NCT00543725: TMC-278-TiDP6-C215: A clinical trial in treatment naive HIV-subjects patients comparing TMC-278 to efavirenz in combination with 2 nucleoside/nucleotide reverse transcriptase inhibitors. CLINICALTRIALS.GOV 2008 May 29
47. 920393 Annex to the examination report of EP-01419152. European Patent Office COMPANY PUBLICATION 2006 December 15 920428 NCT00654147: Raltegravir + lopinavir/ritonavir or emtricitabine/tenofovir for HIV treatment naive subjects. CLINICALTRIALS.GOV 2008 May 08
48. 920430 NCT00632970: Raltegravir vs lopinavir/ritonavir, both in combination with Truvada, in HIV+ treatment naive individuals. CLINICALTRIALS.GOV 2008 March 10
49. 920477 NCT00303576: A safety and tolerability study of dapivirine (TMC-120) vaginal microbicide gel. CLINICALTRIALS.GOV 2006 July 28
50. 920577 INTELENCE (etravirine) tablets. Tibotec BVBA DRUG PACKAGE INSERT 2008 January 18
51. 920582 Cardiovascular disease prevention and treatment in patients with human immunodeficiency virus. Magen E, Elbirt D, Sthoeger Z ISR MED ASSOC J 2005 7 4 252-256
52. 925961 Tibotec conducts two pivotal phase III clinical trials studying TMC-278 in treatment-naive adults with HIV. Tibotec Pharmaceuticals PRESS RELEASE 2008 July 17