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REVIEW

New therapeutic agents in the management of HIV: an overview of darunavir for clinicians

Jessica Rotty A C and Jennifer Hoy A B
+ Author Affiliations
- Author Affiliations

A Infectious Diseases Unit, Alfred Hospital, Commercial Road, Melbourne, Vic. 3004, Australia.

B Department of Medicine, Monash University, Melbourne, Vic. 3168, Australia.

C Corresponding author. Email: j.rotty@alfred.org.au

Sexual Health 5(3) 235-241 https://doi.org/10.1071/SH08005
Submitted: 15 January 2008  Accepted: 16 April 2008   Published: 6 August 2008

Abstract

This overview will provide the reader with summarised information about darunavir, a new protease inhibitor licenced for the treatment of drug resistant HIV-infection. Darunavir is a promising new drug with good clinical efficacy data and safety profile. In this overview clinicians will be updated on clinical efficacy data, side-effects, resistance profile and drug interactions. The overview should give clinicians a sound understanding of when and how to use this new protease inhibitor in the treatment of HIV-infection.

Additional keywords: drug resistance, HAART, Prezista, protease inhibitor.


References


[1] Busse KHS,  Penzak SR. Darunavir: a second-generation protease inhibitor. Am J Health Syst Pharm 2007; 64 1593–602.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[2] Katlama C,  Esposito R,  Gatell JM,  Goffard J-C,  Grinsztejn B,  Pozniak A, et al. Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1. AIDS 2007; 21 395–402.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[3] Haubrich R,  Berger D,  Chiliade P,  Colson A,  Conant M,  Gallant J, et al. Week 24 efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients. AIDS 2007; 21 F11–8.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[4] Molina JM,  Cohen C,  Katlama C,  Grinszstein B,  Timerman A,  de Jesus PR, et al. Safety and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced patients. J Acquir Immune Defic Syndr 2007; 46 24–31.
CAS | PubMed |

[5] Clotet B,  Bellos N,  Molina J-M,  Cooper D,  Goffard J-C,  Lazzarin A, 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; 369 1169–78.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[6] Madruga JV,  Berger D,  McMurchie M,  Suter F,  Banhegyi D,  Ruxrungtham K, 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; 370 49–58.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[7] DeJesus E, Ortiz R, Khanlou H, Voronin E, Van Luzen J, Andrade-Villanueva J, et al. Efficacy and safety of darunavir/ritonavir vs lopinavir/ritonavir in ARV treatment naive HIV-1-infected patients at week 48: ARTEMIS. Proceedings of the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007; Chicago, Illinois, USA.

[8] Lazzarin A,  Campbell T,  Clotet B,  Johnson M,  Katlama C,  Moll A, et al. 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; 370 39–48.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[9] Madruga JV,  Cahn P,  Grinsztejn B,  Haubrich R,  Lalezari J,  Mills A, et al. 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; 370 29–38.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[10] De Meyer S,  Azijn H,  Surleraux D,  Jochmans D,  Tahri A,  Pauwels R, 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; 49 2314–21.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[11] Collier ACGJ , Katner HP , Rozembaum W , Vangeneugden T , Lefebvre E . Safety and efficacy of TMC114/r (darunavir/ritonavir) by gender, age and race: combined 24-week analysis of POWER 1, 2 and 3. Program and abstract of the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy 2006; San Francisco, California, USA. Abstract H-1396.

[12] Prezista Product Information. December 2007; Prezista USA Product Information available online at: http://www.prezista.com/docs/us_package_insert.pdf[verified December 2007].

[13] Sekar V,  Kestens D,  Spinosa-Guzman S,  De Pauw M,  De Paepe E,  Vangeneugden T, et al. The effect of different meal types on the pharmacokinetics of darunavir (TMC114)/ritonavir in HIV-negative healthy volunteers. J Clin Pharmacol 2007; 47 479–84.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[14] Sekar VJ,  Lefebvre E,  De Marez T,  Spinosa-Guzman S,  De Pauw M,  De Paepe E, et al. Pharmacokinetics of darunavir (TMC114) and atazanavir during coadministration in HIV-negative, healthy volunteers. Drugs R D 2007; 8 241–8.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[15] Scholler-Gyure M,  Kakuda TN,  Sekar V,  Woodfall B,  De Smedt G,  Lefebvre E, et al. Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HIV-negative volunteers. Antivir Ther 2007; 12 789–96.
CAS | PubMed |

[16] Johnson VA,  Brun-Vezinet F,  Clotet B,  Gunthard HF,  Kuritzkes DR,  Pillay D, et al. Update of the drug resistance mutations in HIV-1: 2007. Top HIV Med 2007; 15 119–25.
PubMed |

[17] De Meyer S, De Paepe E, Vangeneugden T, Van Baelen B, Spinosa-Guzman S, Lefebvre E, et al. Effect of baseline and on-treatment mutations on the antiviral activity of darunavir/ritonavir and lopinavir/ritonavir: results of a randomised, controlled, phase III study (TITAN). Proceedings of the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2007: Sydney, Australia. Abstract WEPEB038.

[18] Haubrich R. Defining HIV susceptibility to new antiretroviral agents–darunavir. J Infect Dis 2007; 196 1125–7.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[19] Mitsuya Y,  Liu ,  TF ,  Rhee ,  S-Y ,  Fessel ,  WJ ,  Shafer ,  RW . Prevalence of darunavir resistance-associated mutations: patterns of occurrence and association with past treatment. J Infect Dis 2007; 196 1177–9.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

[20] De Meyer S, Dierynck I, Lathouwers E, Van Baelen B, Vangeneugden T, Spinoso-Guzman S, et al. Identification of mutations predictive of a diminished response to darunavir/ritonavir: analysis of data from treatment-experienced patients in POWER 1, 2, 3 and DUET-1 and DUET-2. Presented at the 6th European HIV Drug Resistance Workshop, Budapest, Hungary, 26–28 March 2008.

[21] De Meyer S, Vangeneugden T, Lefebvre E, Van Marck H, Azijn H, De Baere I, et al. Phenotypic and genotypic determination of resistance to TMC114: pooled analysis of POWER 1, 2, and 3. Proceedings of the 8th International Congress on Drug Therapy in HIV Infection; 2006; Glasgow, Scotland. Abstract P196.

[22] Coakley E , Benhamida J, Picchio G , de Bethune MP. Defining the upper and lower phenotypic clinical cut-offs for darunavir/ritonavir by the PhenoSense assay. Proceedings of the 14th Conference on Retroviruses and Opportunistic Infections; 2007; Los Angeles, California, USA. Poster 160.

[23] Parkin N , Stawiski E , Chappey C , Coakley E . Darunavir/amprenavir cross-resistance in clinical samples submitted for phenotype/genotype combination resistance testing. Proceedings of the 14th Conference on Retroviruses and Opportunistic Infections; 2007; Los Angeles, California, USA. Poster 607.

[24] Sekar V , De Meyer S , Vangeneugden T , Lefebvre E , De Pauw M , Van Baelen E et al Absence of darunavir exposure-efficacy and exposure-safety relationships in POWER 3. AIDS 2006 – Proceedings of the 16th International AIDS Conference; 2006; Toronto, Canada. Abstract TUPE0078.