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01.12.2007 | Adis Drug Profile

Darunavir

In the Treatment of HIV-1 Infection

verfasst von: Caroline Fenton, Caroline M. Perry

Erschienen in: Drugs | Ausgabe 18/2007

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Abstract

▲ Darunavir (TMC114) is a nonpeptidic peptidomimetic HIV protease inhibitor (PI), with a high binding affinity and a close fit within the substrate envelope.
▲ Darunavir shows potent in vitro activity against a broad range of clinical isolates of HIV type 1 (HIV-1), including those with decreased susceptibility to most available PIs.
▲ The bioavailability of oral darunavir is increased when it is coadministered with ritonavir. Thus, darunavir must be administered in combination with low-dose (100mg) ritonavir.
▲ In the POWER 1 and POWER 2 trials, two 144-week randomised phase IIb trials, a reduction in plasma HIV-1 RNA levels of ≥1 log 10 copies/mL (primary endpoint) occurred in 77% and 62% of treatment-experienced recipients of darunavir plus ritonavir (darunavir/ritonavir) 600mg/100mg twice daily (in combination with an optimised background regimen) [vs 25% and 14% of control PI (CPI) recipients; p < 0.001] at week 24. Results are from primary analyses (n = 301 and 201).
▲ In a pooled subgroup analysis of data from the POWER 1 and 2 trials, reductions in HIV-1 RNA levels of ≥1 log 10 copies/mL were achieved in 61% of patients treated with darunavir/ritonavir 600mg/ 100mg twice daily versus 15% of CPI recipients (p < 0.0001) at week 48.
▲ Darunavir/ritonavir 600mg/100mg was generally well tolerated in the POWER 1 and 2 trials, with a tolerability profile similar to that of comparator CPIs.

The use of trade names is for product identification purposes only and does not imply endorsement.

Department of Health and Human Services. Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents [online]. Available from URL: http://www.aidsinfo.nih.gov/contentfiles/AdultsandAdolescentsGL.pdf [Accessed 2007 Aug 25]

Gazzard on behalf of the BHIVA Writing Committee. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006). HIV Med 2006; (7): 487–503

The EACS Executive Committee. European Guidelines for the clinical management and treatment of HIV infected adults [online]. Available from URL: http://www.eacs.wa [Accessed 2007 Aug 25]

De Meyer S, Azijn H, Surleraux D, et al. TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother 2005 Jun; 49(6): 2314–21PubMedCrossRef

Volberding PA. Meeting challenges: overcoming limitations. Advances of the protease inhibitor class: proceedings of an Expert Roundtable. J Acquir Immune Defic Syndr 2004; 35 Suppl. 1: S1–2CrossRef

Tibotec. PREZISTA™ (darunavir) summary of product characteristics, [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/prezista/H707-PI-en.pdf [Accessed 2007 Dec 1]

Tibotec Therapeutics. PREZISTATM US prescribing information [online]. Available from URL: http://www.prezista.com/docs/us_package_insert.pdf [Accessed 2007 Dec 1]

Boffito M, Moyle GJ. Pharmacokinetic considerations for combining 2 protease inhibitors. AIDS Read 2004; 14(3): 110–6PubMed

King NM, Prabu-Jeyabalan M, Nalivaika EA, et al. Structural and thermodynamic basis for the binding of TMC114, a next-generation human immunodeficiency virus type 1 protease inhibitor. J Virol 2004 Nov; 78(21): 12012–21PubMedCrossRef

10.

Koh Y, Nakata H, Maeda K, et al. Novel bis-tetrahydrofurany-lurethane-containing nonpeptide protease inhibitor (PI) IUC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. Antimicrob Agents Chemother 2003 Oct; 47(10): 3123–9PubMedCrossRef

11.

Tie Y, Boross PI, Wang YF, et al. High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. J Mol Biol 2004 Apr 23; 338(2): 341–52PubMedCrossRef

12.

Turner D, Schapiro JM, Brenner BG, et al. The influence of protease inhibitor resistance profiles on selection of HIV therapy in treatment-naive patients. Antiviral Ther 2004; 9(3): 301–14

13.

Molla A, Kohlbrenner W. Evolving therapeutic paradigms for HIV and HCV. Curr Opin Biotechnol 2003; 14(6): 634–40PubMedCrossRef

14.

De Meyer S, Hill A, De Baere I, et al. Effect of baseline susceptibility and on-treatment mutations on TMC114 and control PI efficacy [oral presentation]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–9; Denver (CO)

15.

Sekar V, De Meyer S, Vangeneugden T, et al. Pharmacokinetic/ pharmacodynamic(PK/PD) analyses of TMC114 in the POW-ER 1 and POWER 2 trials in treatment-experienced HIV-infected patients [poster]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–9; Denver (CO)

16.

De Meyer S, Hill A, De Baere, et al. Effect of baseline susceptibility and on-treatment mutations on TMC114 and control PI efficacy: preliminary analysis of data from Pi-experienced patients from POWER 1 and POWER 2 [abstract and poster]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–9; Denver (CO)

17.

Pozniak A. Efficacy of TMC114/r in treatment-experienced HIV patients: factors influencing outcome in the pooled 24 week analysis of POWER 1, 2 and 3 [abstract no. P3]. 12th Annual Conference of the British HIV Association; 2006 Mar 29–Apr 1; Brighton

18.

Picchio G, Vangeneugden T, Van Baelen B, et al. Prior utilization or resistance to amprenavir at screening has minimal effect on the 48-week response to darunavir/r in the POWER 1, 2, and 3 studies [abstract no. 609]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

19.

Molina JM, Cohen C, Katlama C, et al. Safety and efficacy of darunavir (TMC114) With low-dose ritonavir in treatment-experienced Patients: 24-week results of POWER 3. J Acquir Immune Defic Syndr 2007 Jul 5; 46(1): 24–31PubMed

20.

Arasteh K, Clumeck N, Pozniak A, et al. TMC114/ritonavir substitution for protease inhibitor(s) in a non-suppressive antiretroviral regimen: a 14-day proof-of-principle trial. AIDS 2005 Jun 10; 19(9): 943–7PubMedCrossRef

21.

Hoetelmans R, Marien K, De Pauw M, et al. Pharmacokinetic interaction between TMC114/ritonavir (RTV) and tenofovir in healthy volunteers [abstract no. TuPeB4634]. eJournal of the International AIDS Society 2004 Jul 11; 6 (3)

22.

Hoetelmans RMW, Lasure A, Koester A, et al. The effect of TMC114, a potent next-generation HIV protease inhibitor, with low-dose ritonavir on atorvastatin pharmacokinetics [abstract no. H-865]. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2004 Oct 30–Nov 2; Washington, DC

23.

Sekar V, Hoetelmans R, De Marez T, et al. Pharmacokinetics of TMC114: effect of omeprazole and ranitidine [abstract no. WePe3.3C13]. 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment; 2005 Jul 24–27; Rio de Janiero

24.

Hoetelmans R, Lefebvre E, van der Sandt I, et al. Pharmacokinetics and effect of food on TMC114, a potent next generation protease inhibitor, boosted with low dose ritonavir [abstract plus poster]. 5th International Workshop on Clinical Pharmacology of HIV therapy; 2004 Apr 1–3; Rome

25.

Hoetelmans R, Van der Sandt I, De Pauw M, et al. TMC 114, a next generation HIV protease inhibitor: pharmacokinetics and safety following oral administration of multiple doses with and without low doses of ritonavir in healthy volunteers [abstract no. 549]. 10th Conference on Retroviruses and Opportunistic Infections; 2003 Feb 10–14; Boston (MA)

26.

Sekar V, Kestens D, Spinosa-Guzman S, et al. The effect of different meal types on the pharmacokinetics of darunavir (TMC114)/ritonavir in HIV-negative healthy volunteers. J Clin Pharmacol 2007 Apr; 47(4): 479–84PubMedCrossRef

27.

Boffito M, Winston A, Fletcher C, et al. Pharmacokinetics (PK) and antiretroviral (ARV) response to TMC 114/r and TMC 125 combination in patients with high level viral resistance [abstract]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–9; Denver (CO)

28.

Arasteh K, Clumeck N, Pozniak A, et al. Antiretroviral activity, safety and pharmacokinetics of TMC 114, a next-generation HIV-1 protease inhibitor (PI), in multiple Pi-experienced patients [abstract]. 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment LBA; 2003 Jul 13–16; Paris

29.

Peeters M, Van Baelen B, De Meyer S, et al. TMC114/RTV activity in multiple Pi-experienced patients: correlation of baseline genotype, phenotype, pharmacokinetics, and IQ with antiviral activity at day 14 [abstract no. 533]. 11th Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8–11; San Francisco (CA)

30.

Sekar VJ, Spinosa-Guzman S, De Paepe E, et al. Pharmacokinetics of multiple-dose darunavir in combination with low-dose ritonavir in individuals with impaired hepatic function [abstract no. TUPDB05]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; Sydney

31.

Hoetelmans R, van der Sandt I, De Pauw M, et al. TMC114, a next generation HIV protease inhibitor: pharmacokinetics and safety following oral administration of multiple doses with and without low doses of ritonavir in healthy volunteers [abstract no. 39]. 4th International Workshop on Clinical Pharmacology of HIV Therapy; 2003 Mar 27–29; Cannes

32.

Sekar V, De Marez T, Spinosa-Guzman S, et al. Pharmacokinetic interaction between TMC114/ritonavir and atazanavir in healthy volunteers [abstract no. PE4.3/4 plus poster]. 10th European AIDS conference; 2005 Nov 17–20; Dublin

33.

Sekar VJ, Lefebvre E, De Paepe E, et al. Pharmacokinetic interaction between TMC114/r and omeprazole or ranitidine in HIV-negative healthy volunteers. Antimicrob Agents Chemother 2007 Mar; 51(3): 958–61PubMedCrossRef

34.

Sekar VJ, Lefebvre E, Boogaerts G, et al. Pharmacokinetic interaction between the protease inhibitors TMC114 and lopinavir/ritonavir [abstract]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA). 2006

35.

Sekar VJ, Lefebvre E, De Marez T, et al. Pharmacokinetic interaction between TMC114, a new protease inhibitor and sildenafil [abstract]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)

36.

Pecini R, Vangeneugden T, Sekar V. Darunavir in combination with other medications: pharmacokinetic interactions [poster S3-5]. American Conference for the Treatment of HIV (AC-THIV); 2007 May 31–Jun 3; Dallas (TX)

37.

Sekar VJ, Spinosa-Guzman S, De Paepe E, et al. Pharmacokinetic interaction trial between darunavir in combination with low-dose ritonavir and didanosine [abstract no. M15682]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; Sydney

38.

Sekar VJ, De Pauw M, Marien K, et al. Pharmacokinetic interaction between TMC114/r and efavirenz in healthy volunteers. Antivir Ther 2007; 12(4): 509–14PubMed

39.

Katlama C, Esposito R, Gatell JM, et al. Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1. AIDS 2007 Feb 19; 21(4): 395–402PubMedCrossRef

40.

Haubrich R, Berger D, Chiliade P, et al. Week 24 efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients. AIDS 2007 Mar 30; 21(6): F11–8PubMedCrossRef

41.

Clotet B, Bellos N, Molina JM, et al. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet 2007 Apr 7; 369(9568): 1169–78PubMedCrossRef

42.

Madruga JV, Berger D, McMurchie M, et al. Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial. Lancet 2007 Jul 7; 370(9581): 49–58PubMedCrossRef

43.

Valdez-Madruga J, Berger DE, McMurchie M, et al. Comparison of 48-week efficacy and safety of darunavir/ritonavir (DRV/r) with lopinavir/ritonavir (LPV/r) in LPV/r-naive, treatment-experienced patients: a randomised, controlled phase III trial (TITAN) [abstract no. TUAB101; plus oral presentation]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; Sydney

44.

Tibotec Pharmaceuticals Limited. TMC114-C211: trial of an investigational protease inhibitor TMC114 with ritonavir (TMC 114/r) in HIV-1 infected patients who have never been treated with antiretroviral medications [online]. Available from URL: http://www.clinicaltrials.gov/ct/show/NCT00258557 [Accessed 2006 Feb 20]

45.

Rachlis A, Clotet B, Baxter J, et al. Safety, tolerability, and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced, hepatitis B or C co-infected patients in POWER 1 and 3. HIV Clin Trials 2007 Jul 31; 8(4): 213–20PubMedCrossRef

Titel: Darunavir
In the Treatment of HIV-1 Infection
verfasst von: Caroline Fenton
Caroline M. Perry
Publikationsdatum: 01.12.2007
Verlag: Springer International Publishing
Erschienen in: Drugs / Ausgabe 18/2007
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI: https://doi.org/10.2165/00003495-200767180-00010

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Darunavir

In the Treatment of HIV-1 Infection

Abstract

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

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