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Darunavir: A Review of Its Use in the Management of HIV-1 Infection

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Abstract

The latest HIV-1 protease inhibitor (PI) darunavir (Prezista™) has a high genetic barrier to resistance development and is active against wild-type HIV and HIV strains no longer susceptible to some older PIs. Ritonavir-boosted darunavir, as a component of antiretroviral therapy (ART), is indicated for the treatment of HIV-1 infection in adult and paediatric patients (aged ≥3 years), with or without treatment experience (details vary depending on region of approval). Several open-label or partially-blinded trials have evaluated the efficacy of ritonavir-boosted darunavir ART regimens for up to 192 weeks in these settings. In treatment-naïve adults, once-daily boosted darunavir was no less effective in establishing virological suppression than once- or twice-daily boosted lopinavir, yet was more effective at maintaining suppression long term. Moreover, treatment-experienced adults with no darunavir resistance-associated mutations (RAMs) had no less effective viral load suppression with once-daily than with twice-daily boosted darunavir. In treatment-experienced adults, including some with multiple major PI RAMs, twice-daily boosted darunavir was more effective than twice-daily boosted lopinavir or boosted control PIs in reducing viral load, and provided virological benefit as part of a salvage regimen in those with few remaining treatment options. Boosted darunavir also reduced viral load when administered once-daily in treatment-naïve adolescents or twice-daily in treatment-experienced children and adolescents. Boosted darunavir is generally well tolerated, with gastrointestinal disturbances and lipid abnormalities among the most common tolerability issues. It has a lipid profile more favourable than that of boosted lopinavir in terms of total cholesterol and triglyceride changes and, when administered once daily, its lipid effects are generally similar to those of boosted atazanavir. Thus, boosted darunavir is a useful option for the ART regimens of adult and paediatric patients with HIV-1 infection.

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References

  1. Le Douce V, Janossy A, Hallay H, et al. Achieving a cure for HIV infection: do we have reasons to be optimistic? J Antimicrob Chemother. 2012;67(5):1063–74.

    Article  PubMed  Google Scholar 

  2. Mothi SN, Karpagam S, Swamy VH, et al. Paediatric HIV—trends & challenges. Indian J Med Res. 2011;134(6):912–9.

    Article  CAS  PubMed  Google Scholar 

  3. Arts EJ, Hazuda DJ. HIV-1 antiretroviral drug therapy. Cold Spring Harb Perspect Med. 2012;2(4):a007161.

    Article  PubMed  Google Scholar 

  4. Kuritzkes DR. Drug resistance in HIV-1. Curr Opin Virol. 2011;1(6):582–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Williams I, Churchill D, Anderson J, et al. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012. HIV Med. 2012;13 Suppl 2:1–85. Plus an update available at http://www.bhiva.org/documents/Conferences/Autumn2013/presentations/131114/DuncanChurchill.pdf. Accessed 26 Nov 2013.

  6. European AIDS Clinical Society. Guidelines version 7.0. 2013. http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf. Accessed 18 Nov 2013.

  7. US Department of Health and Human Services panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents; 2013. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed 18 Nov 2013. Plus an update available at http://aidsinfo.nih.gov/news/1392/hhs-panel-on-antiretroviral-guidelines-for-adults-and-adolescents-updates-recommendations-on-preferred-insti-based-regimens-for-art-naive-individuals. Accessed 26 Nov 2013.

  8. Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA. 2012;308(4):387–402.

    Article  CAS  PubMed  Google Scholar 

  9. Welch S, Sharland M, Lyall EG, et al. PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. HIV Med. 2009;10(10):591–613.

    Article  CAS  PubMed  Google Scholar 

  10. US Department of Health and Human Services panel on antiretroviral therapy and medical management of HIV-infected children. Guidelines for the use of antiretroviral agents in pediatric HIV infection; 2012. http://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf. Accessed 18 Nov 2013.

  11. Maltez F, Doroana M, Branco T, et al. Recent advances in antiretroviral treatment and prevention in HIV-infected patients. Curr Opin HIV AIDS. 2011;6 Suppl 1:S21–30.

    Article  PubMed  Google Scholar 

  12. Arribas JR. Drugs in traditional drug classes (nucleoside reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor/protease inhibitors) with activity against drug-resistant virus (tipranavir, darunavir, etravirine). Curr Opin HIV AIDS. 2009;4(6):507–12.

    Article  PubMed  Google Scholar 

  13. Janssen-Cilag International NV. Prezista: EU summary of product characteristics; 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000707/WC500041756.pdf. Accessed 14 Nov 2013.

  14. Janssen Pharmaceuticals Inc. Prezista (darunavir): US prescribing information; 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021976s033_202895s010lbl.pdf. Accessed 14 Nov 2013.

  15. McKeage K, Perry CM, Keam SJ. Darunavir: a review of its use in the management of HIV infection in adults. Drugs. 2009;69(4):477–503.

    Article  CAS  PubMed  Google Scholar 

  16. Fenton C, Perry CM. Darunavir: in the treatment of HIV-1 infection. Drugs. 2007;67(18):2791–801.

    Article  CAS  PubMed  Google Scholar 

  17. Sauzullo I, Mengoni F, Ermocida A, et al. Pharmacological modulation of apoptosis of PBMC by darunavir and maraviroc [abstract no. PO11]. Infection. 2011;39 Suppl 1:S59.

    Google Scholar 

  18. Martinez E, Gonzalez-Cordon A, Podzamczer D, et al. Metabolic effects of atazanavir/ritonavir vs darunavir/ritonavir in combination with tenofovir/emtricitabine in antiretroviral-naive patients (ATADAR Study) [abstract no. 0423]. J Int AIDS Soc. 2012;15 Suppl 4:18202.

    Google Scholar 

  19. Kakuda TN, Tomaka F, Van De Casteele T, et al. Generalised additive model analysis of the relationship between darunavir pharmacokinetics and pharmacodynamics following once-daily darunavir/ritonavir 800/100 mg treatment in the phase III trials, ARTEMIS and ODIN [abstract no. P072]. 11th International Congress on Drug Therapy in HIV Infection; 11–15 Nov 2012; Glasgow.

  20. Violari A, Bologna R, Kumarasamy N, et al. Safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients aged 3 to < 6 years: week 48 analysis of the ARIEL trial [abstract no. MOAB0102]. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 30 Jun–3 Jul 2013; Kuala Lumpur.

  21. Violari A, Bologna R, Kimutai R, et al. ARIEL: 24-week safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients aged 3 to <6 years [abstract no. 713 plus poster]. 18th Conference on Retroviruses and Opportunistic Infections; 27 Feb–2 Mar 2011; Boston (MA).

  22. US FDA Center for Drug Evaluation and Research. Application number 21-976: microbiology review; 2005. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021976s000_Sprycel_MicroR.pdf. Accessed 18 Nov 2013.

  23. Koh Y, Matsumi S, Das D, et al. Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization. J Biol Chem. 2007;282(39):28709–20.

    Article  CAS  PubMed  Google Scholar 

  24. 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;78(21):12012–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Nivesanond K, Peeters A, Lamoen D, et al. Conformational analysis of TMC114, a novel HIV-1 protease inhibitor. J Chem Inf Model. 2008;48(1):99–108.

    Article  CAS  PubMed  Google Scholar 

  26. Dierynck I, De Wit M, Gustin E, et al. Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007;81(24):13845–51.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Koh Y, Aoki M, Danish ML, et al. Loss of protease dimerization inhibition activity of darunavir is associated with the acquisition of resistance to darunavir by HIV-1. J Virol. 2011;85(19):10079–89.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. 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;49(6):2314–21.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Dierynck I, De Meyer S, Lathouwers E, et al. In vitro susceptibility and virological outcome to darunavir and lopinavir are independent of HIV type-1 subtype in treatment-naive patients. Antivir Ther. 2010;15(8):1161–9.

    Article  CAS  PubMed  Google Scholar 

  31. Orkin C, Dejesus E, Khanlou H, et al. Final 192-week efficacy and safety of once-daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV-1-infected treatment-naive patients in the ARTEMIS trial. HIV Med. 2013;14(1):49–59.

    Article  CAS  PubMed  Google Scholar 

  32. Cahn P, Fourie J, Grinsztejn B, et al. Week 48 analysis of once-daily vs. twice-daily darunavir/ritonavir in treatment-experienced HIV-1-infected patients. AIDS. 2011;25(7):929–39.

    Article  CAS  PubMed  Google Scholar 

  33. Lathouwers E, De La Rosa G, Van de Casteele T, et al. Virological analysis of once-daily and twice-daily darunavir/ritonavir in the ODIN trial of treatment-experienced patients. Antivir Ther. 2013;18(3):289–300.

    Article  CAS  PubMed  Google Scholar 

  34. De Meyer S, Vangeneugden T, van Baelen B, et al. Resistance profile of darunavir: combined 24-week results from the POWER trials. AIDS Res Hum Retroviruses. 2008;24(3):379–88.

    Article  PubMed  Google Scholar 

  35. Banhegyi D, Katlama C, da Cunha CA, et al. Week 96 efficacy, virology and safety of darunavir/r versus lopinavir/r in treatment-experienced patients in TITAN. Curr HIV Res. 2012;10(2):171–81.

    Article  CAS  PubMed  Google Scholar 

  36. Blanche S, Bologna R, Cahn P, et al. Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents. AIDS. 2009;23(15):2005–13.

    Article  CAS  PubMed  Google Scholar 

  37. Poveda E, Anta L, Blanco JL, et al. Drug resistance mutations in HIV-infected patients in the Spanish drug resistance database failing tipranavir and darunavir therapy. Antimicrob Agents Chemother. 2010;54(7):3018–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Descamps D, Lambert-Niclot S, Marcelin A-G, et al. Mutations associated with virological response to darunavir/ritonavir in HIV-1-infected protease inhibitor-experienced patients. J Antimicrob Chemother. 2009;63(3):585–92.

    Article  CAS  PubMed  Google Scholar 

  39. Dailly E, Rodallec A, Allavena C, et al. Virological response to darunavir in patients infected with HIV is linked to darunavir resistance-associated mutations corrected by the count of mutations with positive impact and is not associated with pharmacological and combined virological/pharmacological parameters. Fundam Clin Pharmacol. 2012;26(4):538–42.

    Article  CAS  PubMed  Google Scholar 

  40. Molto J, Santos JR, Perez-Alvarez N, et al. Darunavir inhibitory quotient predicts the 48-week virological response to darunavir-based salvage therapy in human immunodeficiency virus-infected protease inhibitor-experienced patients. Antimicrob Agents Chemother. 2008;52(11):3928–32.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Pellegrin I, Wittkop L, Joubert LM, et al. Virological response to darunavir/ritonavir-based regimens in antiretroviral-experienced patients (PREDIZISTA study). Antivir Ther. 2008;13(2):271–9.

    CAS  PubMed  Google Scholar 

  42. Delaugerre C, Buyck JF, Peytavin G, et al. Factors predictive of successful darunavir/ritonavir-based therapy in highly antiretroviral-experienced HIV-1-infected patients (the DARWEST study). J Clin Virol. 2010;47(3):248–52.

    Article  CAS  PubMed  Google Scholar 

  43. Fagard C, Colin C, Charpentier C, et al. Long-term efficacy and safety of raltegravir, etravirine, and darunavir/ritonavir in treatment-experienced patients: week 96 results from the ANRS 139 TRIO trial. J Acquir Immune Defic Syndr. 2012;59(5):489–93.

    Article  CAS  PubMed  Google Scholar 

  44. 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;370(9581):49–58.

    Article  CAS  PubMed  Google Scholar 

  45. 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;369(9568):1169–78.

    Article  CAS  PubMed  Google Scholar 

  46. Ortiz R, Dejesus E, Khanlou H, et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS. 2008;22(12):1389–97.

    Article  CAS  PubMed  Google Scholar 

  47. Mills AM, Nelson M, Jayaweera D, et al. Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS. 2009;23(13):1679–88.

    Article  CAS  PubMed  Google Scholar 

  48. Taiwo B, Zheng L, Gallien S, et al. Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262). AIDS. 2011;25(17):2113–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Pozniak A, Arasteh K, Molina JM, et al. POWER 3 analysis: 144-week efficacy and safety results for darunavir/ritonavir 600/100 mg bid in treatment-experienced HIV patients [poster]. 9th International Conference on Drug Therapy in HIV Infection; 9–13 Nov 2008; Glasgow.

  50. Arasteh K, Yeni P, Pozniak A, et al. Efficacy and safety of darunavir/ritonavir in treatment-experienced HIV type-1 patients in the POWER 1, 2 and 3 trials at week 96. Antivir Ther. 2009;14(6):859–64.

    Article  CAS  PubMed  Google Scholar 

  51. Aberg JA, Tebas P, Overton ET, et al. Metabolic effects of darunavir/ritonavir versus atazanavir/ritonavir in treatment-naive, HIV type 1-infected subjects over 48 weeks. AIDS Res Hum Retroviruses. 2012;28(10):1184–95.

    Article  CAS  PubMed  Google Scholar 

  52. Currier JS, Martorell C, Osiyemi O, et al. Effects of darunavir/ritonavir-based therapy on metabolic and anthropometric parameters in women and men over 48 weeks. AIDS Patient Care STDS. 2011;25(6):333–40.

    Article  PubMed  Google Scholar 

  53. McKeage K, Scott LJ. Darunavir: in treatment-experienced pediatric patients with HIV-1 infection. Paediatr Drugs. 2010;12(2):123–31.

    Article  PubMed  Google Scholar 

  54. Poupard M, Boussairi A, Krause J, et al. Darunavir plasma level in HIV overweight patients [abstract no. P78]. J Int AIDS Soc. 2012;15 Suppl 4(6):18359. Plus poster presented at the 11th International Congress on Drug Therapy in HIV Infection; 11–15 Nov 2012; Glasgow.

  55. Colbers A, Molto J, Ivanovic J, et al. A comparison of the pharmacokinetics of darunavir, atazanavir, and ritonavir during pregnancy and post-partum [abstract no. 1013 plus poster]. 19th Conference on Retroviruses and Opportunistic Infections; 5–8 Mar 2012; Seattle (WA).

  56. Capparelli EV, Best BM, Stek A, et al. Pharmacokinetics of darunavir once or twice daily during and after pregnancy [abstract no. P_72]. Rev Antiviral Ther Infect Dis. 2011;8:96–7.

    Google Scholar 

  57. Courbon E, Matheron S, Mandelbrot L, et al. Safety, efficacy and pharmacokinetic of darunavir/ritonavir-containing regimen in pregnant HIV+ women [abstract no. 1011]. 19th Conference on Retroviruses and Opportunistic Infections; 5–8 Mar 2012; Seattle (WA).

  58. Ivanovic J, Bellagamba R, Tempestilli M, et al. Successful use of a darunavir/ritonavir in five pregnant women: pharmacokinetics, efficacy and safety [abstract no. PO42]. Infection. 2011;39 Suppl 1:S70.

    Google Scholar 

  59. Rizzo MG. Safety of boosted-darunavir as part of the HAART prophylaxis regimen during pregnancy [abstract no. P77]. HIV Med. 2013;14 Suppl 2:35.

    Google Scholar 

  60. 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;47(4):479–84.

    Article  CAS  PubMed  Google Scholar 

  61. Patterson K, Jennings S, Falcon R, et al. Darunavir, ritonavir, and etravirine pharmacokinetics in the cervicovaginal fluid and blood plasma of HIV-infected women. Antimicrob Agents Chemother. 2011;55(3):1120–2.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Lambert-Niclot S, Peytavin G, Duvivier C, et al. Low frequency of intermittent HIV-1 semen excretion in patients treated with darunavir-ritonavir at 600/100 milligrams twice a day plus two nucleoside reverse transcriptase inhibitors or monotherapy. Antimicrob Agents Chemother. 2010;54(11):4910–3.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Taylor S, Jayasuriya AN, Berry A, et al. Darunavir concentrations exceed the protein-corrected EC50 for wild-type HIV in the semen of HIV-1-infected men. AIDS. 2010;24(16):2583–7.

    Article  CAS  PubMed  Google Scholar 

  64. Calcagno A, Yilmaz A, Cusato J, et al. Determinants of darunavir cerebrospinal fluid concentrations: impact of once-daily dosing and pharmacogenetics. AIDS. 2012;26(12):1529–33.

    Article  CAS  PubMed  Google Scholar 

  65. Croteau D, Rossi SS, Best BM, et al. Darunavir is predominantly unbound to protein in cerebrospinal fluid and concentrations exceed the wild-type HIV-1 median 90% inhibitory concentration. J Antimicrob Chemother. 2013;68(3):684–9.

    Article  CAS  PubMed  Google Scholar 

  66. Yilmaz A, Izadkhashti A, Price RW, et al. Darunavir concentrations in cerebrospinal fluid and blood in HIV-1-infected individuals. AIDS Res Hum Retroviruses. 2009;25(4):457–61.

    Article  CAS  PubMed  Google Scholar 

  67. Sekar V, Spinosa-Guzman S, De Paepe E, et al. Pharmacokinetics of multiple-dose darunavir in combination with low-dose ritonavir in individuals with mild-to-moderate hepatic impairment. Clin Pharmacokinet. 2010;49(5):343–50.

    Article  CAS  PubMed  Google Scholar 

  68. Kakuda T, Sekar V, Vis P, et al. Pharmacokinetics and pharmacodynamics of darunavir and etravirine in HIV-1-infected, treatment-experienced patients in the Gender, Race, and Clinical Experience (GRACE) trial. AIDS Res Treat. 2012. doi:10.1155/2012/186987.

  69. 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;8(4):213–20.

    Article  PubMed  Google Scholar 

  70. Zorrilla C, Wright R, Osiyemi O, et al. Total and unbound darunavir pharmacokinetics in pregnant women infected with HIV-1: results of a study of darunavir/ritonavir 600/100 mg administered twice daily. HIV Med. 2013. doi:10.1111/hiv.12047.

    PubMed  Google Scholar 

  71. Yazdanpanah Y, Fagard C, Descamps D, et al. High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial. Clin Infect Dis. 2009;49(9):1441–9.

    Article  CAS  PubMed  Google Scholar 

  72. 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;46(1):24–31.

    CAS  PubMed  Google Scholar 

  73. Currier J, Averitt Bridge D, Hagins D, et al. Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial. Ann Intern Med. 2010;153(6):349–57.

    Article  PubMed Central  PubMed  Google Scholar 

  74. Bedimo R, Drechsler H, Cutrell J, et al. RADAR study: week 48 safety and efficacy of raltegravir combined with boosted darunavir compared to tenofovir/emtricitabine combined with boosted darunavir in antiretroviral-naive patients. Impact on bone health [abstract no. WEPE512 plus poster]. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 30 Jun–3 Jul 2013; Kuala Lumpur.

  75. Lewin J. DIONE - 24 week efficacy, safety, tolerability and pharmacokinetics of DRV/r QD in treatment-naive adolescents, 12 to < 18 years [conference report on the 6th International AIDS Society Conference on HIV Pathogenesis Treatment and Prevention]; 2011. http://www.natap.org/2011/IAS/IAS_40.htm. Accessed 24 Sep 2013.

  76. 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;21(4):395–402.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  78. Lazzarin A, Mazzotta F, Mezzaroma I, et al. Health-related quality of life (HRQOL) assessment with once- and twice-daily darunavir/ritonavir (DRV/R) in the ODIN trial [abstract no. PO 26]. Infection. 2011;39 Suppl 1:S63–4.

    Google Scholar 

  79. Katlama C, Bellos N, Grinsztejn B, et al. POWER 1 and 2: combined final 144-week efficacy and safety results for darunavir/ritonavir 600/100 mg bid in treatment-experienced HIV patients [poster]. 9th International Congress on Drug Therapy in HIV Infection; 9–13 Nov 2008; Glasgow.

  80. Fourie J, Flamm J, Rodriguez-French A, et al. Effect of baseline characteristics on the efficacy and safety of once-daily darunavir/ ritonavir in HIV-1-infected, treatment-naive ARTEMIS patients at week 96. HIV Clin Trials. 2011;12(6):313–22.

    Article  CAS  PubMed  Google Scholar 

  81. Smith KY, Garcia F, Kumar P, et al. Assessing darunavir/ritonavir-based therapy in a racially diverse population: 48-week outcomes from GRACE. J Natl Med Assoc. 2012;104(7–8):366–76.

    PubMed  Google Scholar 

  82. Sension M, Cahn P, Domingo P, et al. Subgroup analysis of virological response rates with once- and twice-daily darunavir/ritonavir in treatment-experienced patients without darunavir resistance-associated mutations in the ODIN trial. HIV Med. 2013. doi:10.1111/hiv.12024.

    PubMed  Google Scholar 

  83. Arathoon E, Schneider S, Baraldi E, et al. Effects of once-daily darunavir/ritonavir versus lopinavir/ritonavir on metabolic parameters in treatment-naive HIV-1-infected patients at week 96: ARTEMIS. Int J STD AIDS. 2013. doi:10.1258/ijsa.2012.012120.

    PubMed  Google Scholar 

  84. Simpson KN, Pei PP, Moller J, et al. Lopinavir/ritonavir versus darunavir plus ritonavir for HIV infection: a cost-effectiveness analysis for the United States. Pharmacoeconomics. 2013;31(5):427–44.

    Article  PubMed  Google Scholar 

  85. Thuresson PO, Verheggen B, Heeg B, et al. Cost-effectiveness of atazanavir/r compared to darunavir/r in Germany [abstract no. PIN82]. Value Health. 2011;14(7):A280.

    Article  Google Scholar 

  86. Santos M, Stenut S, Ferraq W, et al. Cost-effectiveness analysis of darunavir versus atazanavir, each in combination with emtricitabine and tenofovir, for the management of naive anti-retroviral HIV infected patients, under the Belgian social security perspective [abstract no. PIN48]. Value Health. 2012;15(7):A393–4.

    Article  Google Scholar 

  87. Brogan AJ, Mrus J, Hill A, et al. Comparative cost-efficacy analysis of darunavir/ritonavir and other ritonavir-boosted protease inhibitors for first-line treatment of HIV-1 infection in the United States. HIV Clin Trials. 2010;11(3):133–44.

    Article  CAS  PubMed  Google Scholar 

  88. Brogan A, Mauskopf J, Talbird SE, et al. US cost effectiveness of darunavir/ritonavir 600/100 mg bid in treatment-experienced, HIV-infected adults with evidence of protease inhibitor resistance included in the TITAN Trial. Pharmacoeconomics. 2010;28 Suppl 1:129–46.

    Article  PubMed  Google Scholar 

  89. Moeremans K, Hemmett L, Hjelmgren J, et al. Cost effectiveness of darunavir/ritonavir 600/100 mg bid in treatment-experienced, lopinavir-naive, protease inhibitor-resistant, HIV-infected adults in Belgium, Italy, Sweden and the UK. Pharmacoeconomics. 2010;28 Suppl 1:147–67.

    Article  PubMed  Google Scholar 

  90. Mauskopf J, Brogan A, Martin S, et al. Cost effectiveness of darunavir/ritonavir in highly treatment-experienced, HIV-1-infected adults in the USA. Pharmacoeconomics. 2010;28 Suppl 1:83–105.

    Article  PubMed  Google Scholar 

  91. Moeremans K, Annemans L, Lothgren M, et al. Cost effectiveness of darunavir/ritonavir 600/100 mg bid in protease inhibitor-experienced, HIV-1-infected adults in Belgium, Italy, Sweden and the UK. Pharmacoeconomics. 2010;28 Suppl 1:107–28.

    Article  PubMed  Google Scholar 

  92. Kim R, Baxter JD. Protease inhibitor resistance update: where are we now? AIDS Patient Care STDS. 2008;22(4):267–77.

    Article  PubMed  Google Scholar 

  93. Wensing AM, van Maarseveen NM, Nijhuis M. Fifteen years of HIV protease inhibitors: raising the barrier to resistance. Antiviral Res. 2010;85(1):59–74.

    Article  CAS  PubMed  Google Scholar 

  94. US National Institutes of Health. ClinicalTrials.gov; 2013. http://www.clinicaltrials.gov. Accessed 19 Nov 2013.

  95. Ananworanich J, Puthanakit T, Saphonn V, et al. Lessons from a multicentre paediatric HIV trial. Lancet. 2008;372(9636):356–7.

    Article  PubMed Central  PubMed  Google Scholar 

  96. Orman JS, Perry CM. Tipranavir: a review of its use in the management of HIV infection. Drugs. 2008;68(10):1435–63.

    Article  CAS  PubMed  Google Scholar 

  97. Boehringer Ingelheim International GmbH. Aptivus (tipranavir): US prescribing information; 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021814s013,022292s006lbl.pdf. Accessed 18 Nov 2013.

  98. Boehringer Ingelheim International GmbH. Aptivus: EU summary of product characteristics; 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000631/WC500025936.pdf. Accessed 18 Nov 2013.

  99. Antoniou T, Raboud JM, Diong C, et al. Virologic and immunologic effectiveness of tipranavir/ritonavir (TPV/r)- versus darunavir/ritonavir (DRV/r)-based regimens in clinical practice. J Int Assoc Physicians AIDS Care (Chic). 2010;9(6):382–9.

    Article  Google Scholar 

  100. Elgadi MM, Piliero PJ. Boosted tipranavir versus darunavir in treatment-experienced patients: observational data from the randomized POTENT trial. Drugs R D. 2011;11(4):295–302.

    Article  PubMed Central  PubMed  Google Scholar 

  101. World Health Organization. HIV drug resistance fact sheet; 2011. http://www.who.int/hiv/facts/drug_resistance/en/. Accessed 27 Sep 2013.

  102. Poveda E, de Mendoza C, Martin-Carbonero L, et al. Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors. J Antimicrob Chemother. 2007;60(4):885–8.

    Article  CAS  PubMed  Google Scholar 

  103. Mitsuya Y, Liu TF, Rhee SY, et al. Prevalence of darunavir resistance-associated mutations: patterns of occurrence and association with past treatment. J Infect Dis. 2007;196(8):1177–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  104. De La Rosa G, Pattery T, Picchio G, et al. Changing prevalence of darunavir resistance associated mutations (DRV RAMs) in clinical samples received for routine resistance testing: 2003–2009 [abstract]. J Int AIDS Soc. 2010;13 Suppl 4:P132.

    Article  Google Scholar 

  105. Marcelin AG, Charpentier C, Wirden M, et al. Darunavir resistance spectrum in darunavir-naive patients harboring virological failure to antiretroviral therapy [abstract]. 10th International Congress on Drug Therapy in HIV Infection; 7–11 Nov 2010; Glasgow.

  106. Naggie S, Hicks C. Protease inhibitor-based antiretroviral therapy in treatment-naive HIV-1-infected patients: the evidence behind the options. J Antimicrob Chemother. 2010;65(6):1094–9.

    Article  CAS  PubMed  Google Scholar 

  107. Arribas JR, Horban A, Gerstoft J, et al. The MONET trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/ml. AIDS. 2010;24(2):223–30.

    Article  CAS  PubMed  Google Scholar 

  108. Katlama C, Valantin MA, Algarte-Genin M, et al. Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136. AIDS. 2010;24(15):2365–74.

    CAS  PubMed  Google Scholar 

  109. Santos JR, Molto J, Llibre JM, et al. Randomised study to evaluate lopinavir/ritonavir vs. darunavir/ritonavir monotherapies as simplification of triple therapy regimens [abstract no. WEPE514 plus poster]. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 30 Jun–3 Jul 2013; Kuala Lumpur.

  110. Overton ET, Arathoon E, Baraldi E, et al. Effect of darunavir on lipid profile in HIV-infected patients. HIV Clin Trials. 2012;13(5):256–70.

    Article  CAS  PubMed  Google Scholar 

  111. Josephson F. Drug-drug interactions in the treatment of HIV infection: focus on pharmacokinetic enhancement through CYP3A inhibition. J Intern Med. 2010;268(6):530–9.

    Article  CAS  PubMed  Google Scholar 

  112. Shah BM, Schafer JJ, Priano J, et al. Cobicistat: a new boost for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2013. doi:10.1002/phar.1237.

    Google Scholar 

  113. Gilead Sciences Intl Ltd. Tybost 150 mg film-coated tablets: EU summary of product characteristics; 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002572/WC500153014.pdf. Accessed 18 Nov 2013.

  114. AIDS.GOV. The global HIV/AIDS crisis today; 2013. http://aids.gov/hiv-aids-basics/hiv-aids-101/global-statistics/. Accessed 27 Sep 2013.

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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    Emma D. Deeks

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The manuscript was reviewed by: J.R. Arribas, Instituto de Investigatión Sanitaria del Hospital La Paz, Madrid, Spain; C. Godfrey, The Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; M.W. Tang, Division of Infectious Diseases, Stanford University Medical Center, Stanford, CA, USA.

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Deeks, E.D. Darunavir: A Review of Its Use in the Management of HIV-1 Infection. Drugs 74, 99–125 (2014). https://doi.org/10.1007/s40265-013-0159-3

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