654
Views
20
CrossRef citations to date
0
Altmetric
Drug Evaluations

Darunavir/cobicistat for the treatment of HIV-1: a new era for compact drugs with high genetic barrier to resistance

, & , MD

References

• The most important epidemiologic data.

  • Dolling D, Sabin C, Delpech V, et al. Has a limit to the decline in transmitted drug resistance been reached? Evidence from a large surveillance study of UK-acquired infections. 19th Conference on Retroviruses and Opportunistic Infections; 2012 Mar 5–8. Seattle. Abstract 732.

• Very relevant drug resistance data.

  • Descamps D, Assoumou L, Charpentier C, et al. Stable prevalence of transmitted drug resistance mutations in ARV-naive chronically HIV+ patients: France, 2006/07 to 2010/11. 19th Conference on Retroviruses and Opportunistic Infections; 2012 Mar 5–8; Seattle. Abstract 73.

• Helpful for understanding epidemiological dynamics of drug resistance.

  • Kim D, Ziebell R, Saduvala N, et al. Trend in transmitted HIV-1 ARV drug resistance-associated mutations: 10 HIV surveillance areas, US, 2007-2010. 20th Conference on Retroviruses and Opportunistic Infections; 2013 Mar 3–6; Atlanta. Abstract 149.

• Helpful for understanding epidemiological dynamics of drug resistance.

• Helpful for understanding epidemiological dynamics of drug resistance.

  • Kotaki T, Khairunisa SQ, Witaningrum AM, et al. HIV-1 transmitted drug resistance mutations among antiretroviral therapy-naïve individuals in Surabaya, Indonesia. AIDS Res Ther. 2015;12:5.

• Helpful for understanding epidemiological dynamics of drug resistance.

  • Casadellà M, Van Ham PM, Noguera-Julian M, et al. Primary resistance to integrase strand-transfer inhibitors in Europe. J Antimicrob Chemother. 2015 Jul 17;pii: dkv202. [Epub ahead of print].

•• Very important recent data of surveillance.

• Useful practical tool.

• Useful practical tool.

• The most useful practical tool.

  • RuelaCorrêa JC, D’Arcy DM, Dos Reis Serra CH, et al. Darunavir: a critical review of its properties, use and drug interactions. Pharmacology. 2012;90:102–109.

• Good-quality review of darunavir.

  • Haubrich R, Berger D, Chiliade P, et al. Week 24 efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients. AIDS. 2007;21:F11–F18.

• Initial, exciting data on salvage therapy.

  • Curran A, Gutirerrez M, Deig E, et al. Efficacy, safety and pharmacokinetics of 900/100 mg of darunavir/ritonavir once daily in treatment-experienced patients. J Antimicrob Chemother. 2010;65:2195–2203.

• First data of once-daily darunavir in non-naïve subjects.

  • Sasková KG, Kozísek M, Rezácová P, et al. Molecular characterization of clinical isolates of human immunodeficiency virus resistant to the protease inhibitor darunavir. J Virol. 2009;83:8810–8818.

• Very relevant virologic data on darunavir.

  • 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):13845–13851.

•• Basic pharmacodynamic data.

  • Lennox JL, Landovitz RJ, Ribaudo HJ, et al. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014 Oct 7;161(7):461–471.

•• One of the most important recent studies of HIV therapy.

•• One of the most important recent studies of HIV therapy.

  • Kakuda TN, Brochot A, Custodio JM, et al. Pharmacokinetics and pharmacodynamics of boosted once-daily darunavir. J Antimicrob Chemother. 2014;69(10):2591–2605.

•• Pharmacologic data of highest relevance to this presentation.

  • 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;21:395–402.

• Exciting historical data of salvage therapy.

  • 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;46:24–31.

• Exciting historical data of salvage therapy.

  • Mascolini M, Boucher C, Larder B, et al. Key reports from the XV international drug resistance workshop 2006. AntivirTher. 2007;12:131–145.
  • Lazzarin A, Campbell T, Clotet B, 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(9581):39–48.

• Important, yet poorly impacting trial of ritonavir-boosted darunavir plus etravirine plus third agent in salvage.

  • Boffito M, Winston A, Jackson A, et al. Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance. AIDS. 2007;21(11):1449–1455.

• Important, yet poorly impacting trial of ritonavir-boosted darunavir plus etravirine plus third agent in salvage therapy.

  • 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):1441–1449.

• Exciting data of salvage therapy combining three new drugs.

  • Bánhegyi 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):171–181.

• One of the main head-to-head studies of darunavir.

  • 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 Apr 24;25(7):929–939.

• Confirmation of the efficacy of once-daily ritonavir-boosted darunavir in non-naive subjects.

  • Gagliardini R, Rossetti B, Bianco C, et al. Safety and therapeutic efficacy of the switch to maraviroc+darunavir/ritonavir in HIV/HCV coinfected patients: initial results from GUSTA study. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19818.

• Intriguing new data of dual therapy.

  • Maggiolo F, Valenti D, Callegaro A, et al. Switch from PI/rtv +2 nucleos(t)ides to RPV+DRV/rtv maintains HIV suppression and is well tolerated (PROBE study). 8th IAS Conference on HIV Pathogenesis Treatment and Prevention; 2015 July 18–22. Vancouver (Canada).

•• Very recent and good data of darunavir-based once daily dual therapy.

  • Ruane PJ, Brinson C, Ramgopal M, et al. INROADS study investigators. The Intelence aNd pRezista Once A Day Study (INROADS): a multicentre, single-arm, open-label study of etravirine and darunavir/ritonavir as dual therapy in HIV-1-infected early treatment-experienced subjects. HIV Med. 2015;16(5):288–296.

•• Very good data of darunavir-based once daily dual therapy.

  • Bedimo RJ, Drechsler H, Jain M, et al. The 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. PLoS One. 2014 Aug 29;9(8):e106221.

• Important metabolic data.

  • Jackson A, Else L, Higgs C, et al. Rilpivirine with darunavir/ritonavir; pharmacokinetics & safety in HIV therapy-naïve patients. Abs. 507, Conference on Retroviruses and Opportunistic Infections (CROI) 2014; 2014 Mar 4–6. Boston (MA).

•• High-quality pharmacokinetic data of an unusual regimen.

  • Sterrantino G, Zaccarelli M, Di Biagio A, et al. Darunavir-based dual therapy of treatment-experienced HIV-infected patients: analysis from a national multicenter database. Infection. 2015 Jun;43(3):339–343.

•• Comprehensive data from a wide national database.

  • Bernardino JI, Zamora FX, Valencia E, et al. Efficacy of a dual therapy based on darunavir/ritonavir and etravirine in ART-experienced patients. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19787.

• Interesting experience of dual therapy.

  • Borghetti A, Mondi A, Piccoli B, et al. Switching to lamivudine plus darunavir/r dual therapy in a cohort of treatment-experienced HIV-positive patients: the experience of an Italian centre. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19817.

• Interesting and daring experience of low-toxicity dual therapy.

•• Perhaps the most important conclusions on PI monotherapy.

  • Antinori A, Arribas J, Fehr J, et al. The PROTEA trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV-1 RNA below 50 copies/mL. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19525.

• Interesting experience of monotherapy.

  • BenMarzouk-Hidalgo OJ, Torres-Cornejo A, Gutiérrez-Valencia A, et al. Differential effects of viremia and microbial translocation on immune activation in HIV-infected patients throughout ritonavir-boosted darunavir monotherapy. Medicine (Baltimore). 2015;94(17):e781.

• Intriguing analysis on an essential issue of monotherapy.

  • Valero IP, Baeza AG, Hernandez-Tamames JA, et al. Cerebral volumes, neuronal integrity and brain inflammation measured by MRI in patients receiving PI monotherapy or triple therapy. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19578.

• Intriguing analysis on an essential issue of monotherapy.

  • Xu L, Liu H, Murray BP, et al. Cobicistat (GS-9350): a potent and selective inhibitor of human CYP3A as a novel pharmacoenhancer. ACS Med Chem Lett. 2010;1(5):209–213.

•• Important pharmacologic data on cobicistat.

• Important pharmacologic data on the combination.

  • Kakuda TN, Van De Casteele T, Petrovic R, et al. Bioavailablity of two fixed-dose combination formulations of darunavir/cobicistat 800/150 mg compared with darunavir 800 mg and ritonavir 100 mg coadministered as single agents. AntivirTher. 2014;19(6):597–606.

• Main formulation-finding study on the combination of the two drugs.

  • Sherman EM, Worley MV, Unger NR, et al. Cobicistat: review of a pharmacokinetic enhancer for HIV infection. ClinTher. 2015 Sep 1;37(9):1876–1893.

• Very comprehensive review on cobicistat.

  • Lepist EI, Phan TK, Anupma R, et al. Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro. Antimicrob Agents Chemother. 2012;56(10):5409–5413.

• At the roots of the introduction of cobicistat.

  • Kakuda TN, Opsomer M, Timmers M, et al. Pharmacokinetics of darunavir in fixed-dose combination with cobicistat compared with coadministration of darunavir and ritonavir as single agents in healthy volunteers. J Clin Pharmacol. 2014;54(8):949–957.

•• Main clinical comparison of the two boosters with darunavir.

  • Tashima K, Crofoot G, Tomaka FL, et al. Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open label single arm trial. AIDS Res Ther. 2014;11:39.

•• The most relevant trial on cobicistat-boosted darunavir to date.

  • Tashima K, Crofoot G, Tomaka FL, et al. Phase IIIb, open-label, single-arm trial of darunavir/cobicistat: week 48 subgroup analysis of HIV-1 infected, treatment- naïve adults. Abs 240, 12th International Congress on Drug Therapy in HIV Infection; 2014 Nov 2–6; Glasgow (UK).
  • Mills A, Ortiz R, Crofoot G, et al. 48 Week study of the first PI-based single tablet regimen (STR) darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) vs. cobicistat (COBI)-boosted darunavir (DRV) and emtricitabine/tenofovirdisoproxilfumarate /F/(TDF) in treatment-naive (TN) adults. Abstract H-647c. Interscience Conference of Antimicrobial Agents and Chemotherapy; 2014 Sep; San Diego (CA).

• First data of a new extremely promising coformulation.

•• Very relevant data on darunavir neurologic kinetics.

• Important data in a delicate setting.

  • Ramgopal M, Osiyemi O, Zorrilla CD, et al. Pharmacokinetics (PK) of etravirine (ETR) in HIV-1– infected pregnant women. 5th International Workshop on HIV &Women; 2015 Feb 21–22; Seattle (WA). Oral abstract 02.

• Important data in a delicate setting.

• Relevant pharmacology data.

  • Bruce RD, Winkle P, Jm C, et al. The phamacokinetic and pharmacodynamic interactions between buprenorphine/naloxone and elvitegravir/cobicistat in subjects receiving chronic buprenorphine/naloxone treatment. J Acquir Immune Defic Syndrome. 2013;63(4):480–484.

• Relevant pharmacology data.

• Very important clinical tool.

  • Ramanathan S, Warren D, Wei L, et al. Pharmacokinetic boosting of atazanavir with the pharmacoenhancer GS-9350 versus ritonavir [poster A1-1301]. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA).
  • Couzigou C, Daudon M, Meynard JL, et al. Urolithiasis in HIV-positive patients treated with atazanavir. Clin Infect Dis. 2007;45(8):e105.
  • Cihlar T, Ray AS, Laflamme G, et al. Molecular assessment of the potential for renal drug interactions between tenofovir and HIV protease inhibitors. AntivirTher. 2007;12:267–272.
  • Lee CG, Gottesman MM, Cardarelli CO, et al. HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter. Biochemistry. 1998;37:3594–3601.
  • Kelly MD, Gibson A, Bartlett H, et al. Tenofovir-associated proteinuria. AIDS. 2013 Jan 28;27(3):479–481.

•• Very important toxicity issue.

  • Gutiérrez F, Fulladosa X, Barril G, et al. Renal tubular transporter-mediated interactions of HIV drugs: implications for patient management. AIDS Rev. 2014 Oct-Dec;16(4):199–212.

• Very good review.

  • Stray KM, Bam RA, Birkus G et al. Evaluation of the effect of cobicistat on the in vitro renal transport and cytotoxicity potential of tenofovir. Antimicrob Ag Chemother. 2103;57(10):4982–4989.

•• Key safety point in present and future antiretroviral therapy.

  • German P, Liu HC, Szwarcberg J, et al. Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function. J Acquir Immune Defic Syndr. 2012;61(1):32–40.

•• Essential study of renal safety.

  • McDonald CK, Martorell C, Ramgopal M, et al. Cobicistat-boosted protease inhibitors in HIV-infected patients with mild to moderate renal impairment. HIV Clin Trials. 2014;15(6):269–273.

• More relevant data on the renal safety of cobicistat.

  • Bagnis CI, Stellbrink H. Protease inhibitors and renal function in patients with HIV infection: a systematic review. Infect Dis Ther. 2015 Mar;4(1):15–50.
  • Elion R, Cohen C, Gathe J, et al. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/tenofovirdf in the initial treatment of HIV infection. AIDS. 2011 Sep 24;25(15):1881–1886.
  • Raffi F, Babiker AG, Richert L, et al. NEAT001/ANRS143 Study Group. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial. Lancet. 2014 Nov 29;384(9958):1942–1951.

•• Very important and still debated milestone of antiretroviral therapy research.

• Essential, still poorly debated issue.

  • Rockstroh JK, DeJesus E, Henry K, et al. Randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013;62:483–486.
  • Guaraldi G, Zona S, Cossarizza A, et al. Switching to darunavir/ritonavir monotherapy vs. triple-therapy on body fat redistribution and bone mass in HIV-infected adults: the Monarch randomized controlled trial. Int J STD AIDS. 2014 Mar; 25(3):207–212. doi:10.1177/0956462413497701. Epub 2013 Aug 28.

•• Essential study and important metabolic analysis.

  • Nigatu T. Integration of HIV and noncommunicable diseases in health care delivery in low- and middle-income countries. Prev Chronic Dis. 2012;9:110331.

• Important Public Health perspective.

• Important Public Health perspective.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.