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Volumn 7, Issue 5, 2012, Pages 390-400

Pharmacology of HIV integrase inhibitors

Author keywords

dolutegravir; elvitegravir; HIV integrase inhibitors; raltegravir

Indexed keywords

ATAZANAVIR; BOCEPREVIR; COBICISTAT; CYTOCHROME P450 3A; CYTOCHROME P450 3A4; DARUNAVIR; DOLUTEGRAVIR; ELVITEGRAVIR; EMTRICITABINE; ENFUVIRTIDE; GLUCURONOSYLTRANSFERASE 1A10; LERSIVIRINE; RALTEGRAVIR; RIBAVIRIN; RIFABUTIN; RIFAMPICIN; RILPIVIRINE; RITONAVIR; TENOFOVIR; TIPRANAVIR;

EID: 84865653643     PISSN: 1746630X     EISSN: 17466318     Source Type: Journal    
DOI: 10.1097/COH.0b013e328356e91c     Document Type: Review
Times cited : (50)

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    • Apr 16-18,; Barcelona, Spain. Abstract O/03. Co-administration of rifabutin and cobicistat-boosted elvitegravir resulted intrough concentrations lower than those expected from data with rifabutin and ritonavir-boosted elvitegravir. This study also assessed pharmacokinetics forelvitegravir/ cobicistat administered with atazanavir or rosuvastatin
    • Ramanathan S, Wang H, Stondell T, et al. Pharmacokinetics and drug interaction profile of cobicistat boosted-EVG with atazanavir, rosuvastatinor rifabutin. 13th International Workshop on Clinical Pharmacology of HIV Therapy; Apr 16-18, 2012; Barcelona, Spain. Abstract O/03. Co-administration of rifabutin and cobicistat-boosted elvitegravir resulted intrough concentrations lower than those expected from data with rifabutin and ritonavir-boosted elvitegravir. This study also assessed pharmacokinetics forelvitegravir/cobicistat administered with atazanavir or rosuvastatin.
    • (2012) 13th International Workshop on Clinical Pharmacology of HIV Therapy
    • Ramanathan, S.1    Wang, H.2    Stondell, T.3
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    • Pharmacokinetic interaction ofritonavir-boosted elvitegravir and maraviroc
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    • Ramanathan, S.1    Abel, S.2    Tweedy, S.3
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    • Pharmacokinetic interaction between elvitegravirritonavir and dose-adjusted rifabutin
    • April 7-9, 2008; New Orleans, LA. Abstract P19
    • German P, West S, Hui J, et al. Pharmacokinetic interaction between elvitegravir/ritonavir and dose-adjusted rifabutin. 9th International Workshopon Clinical Pharmacology of HIV Therapy; April 7-9, 2008; New Orleans, LA. Abstract P19.
    • 9th International Workshopon Clinical Pharmacology Of HIV Therapy
    • German, P.1    West, S.2    Hui, J.3
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    • Effect of acid reducing agents on the relativebioavailability and pharmacokinetics of cobicistat-boosted elvitegravir
    • April 13- 15, 2011; Miami, FL. Abstract P/13
    • Mathias A, Koziara J, Wei L, et al. Effect of acid reducing agents on the relativebioavailability and pharmacokinetics of cobicistat-boosted elvitegravir. 12thInternational Workshop on Clinical Pharmacology of HIV Therapy; April 13- 15, 2011; Miami, FL. Abstract P/13.
    • 12thInternational Workshop on Clinical Pharmacology of HIV Therapy
    • Mathias, A.1    Koziara, J.2    Wei, L.3
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    • 78049297410 scopus 로고    scopus 로고
    • Lack of interaction between the HIV integrase inhibitor S/GSK1349572 and tenofovir in healthy subjects
    • Song I, Min SS, Borland J, et al. Lack of interaction between the HIV integrase inhibitor S/GSK1349572 and tenofovir in healthy subjects. J Acquir ImmuneDefic Syndr 2010; 55:365-367.
    • (2010) J Acquir ImmuneDefic Syndr , vol.55 , pp. 365-367
    • Song, I.1    Min, S.S.2    Borland, J.3
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    • 84886796936 scopus 로고    scopus 로고
    • Effects of enzyme inducers, tipranavir and efavirenz, on the pharmacokinetics of the integrase inhibitor, dolutegravir (S/GSK1359572)
    • April 13-15,rfpy1 2011; Miami, FL.Abstract O/02.Although significant decreases in dolutegravir exposure are observed withboth tipranavir and efavirenz, dolutegravir trough concentrations remain multi-foldabove the IC90
    • Song I, Borland J, Lou Y, et al. Effects of enzyme inducers, tipranavir and efavirenz, on the pharmacokinetics of the integrase inhibitor, dolutegravir (S/GSK1359572). 12th International Workshop onClinical Pharmacology of HIV Therapy; April 13-15, 2011; Miami, FL.Abstract O/02.Although significant decreases in dolutegravir exposure are observed withboth tipranavir and efavirenz, dolutegravir trough concentrations remain multi-foldabove the IC90.
    • 12th International Workshop onClinical Pharmacology of HIV Therapy
    • Song, I.1    Borland, J.2    Lou, Y.3
  • 49
    • 79959244325 scopus 로고    scopus 로고
    • Effects of etravirine alone and with ritonavir-boosted protease inhibitors on the pharmacokinetics of dolutegravir
    • This article explains the clinically important interaction between etravirineand dolutegravir and rescue of dolutegravir's pharmacokinetic profile by coadministrationof boosted protease inhibitors
    • Song I, Borland J, Min S, et al. Effects of etravirine alone and with ritonavir-boosted protease inhibitors on the pharmacokinetics of dolutegravir.Antimicrob Agents Chemother 2011; 55:3517-3521. This article explains the clinically important interaction between etravirineand dolutegravir and rescue of dolutegravir's pharmacokinetic profile by coadministrationof boosted protease inhibitors.
    • (2011) Antimicrob Agents Chemother , Issue.55 , pp. 3517-3521
    • Song, I.1    Borland, J.2    Min, S.3
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    • The effect of lopinavir/ritonavir and darunavir/ ritonavir on the HIV integrase inhibitor S/GSK1349572 in healthy participants
    • This study provides evidence that dolutegravir does not participate in clinicallyimportant interactions with the protease inhibitors lopinavir/ritonavir and darunavir/ritonavir
    • Song I, Min SS, Borland J, et al. The effect of lopinavir/ritonavir and darunavir/ ritonavir on the HIV integrase inhibitor S/GSK1349572 in healthy participants. J Clin Pharmacol 2011; 51:237-242.This study provides evidence that dolutegravir does not participate in clinicallyimportant interactions with the protease inhibitors lopinavir/ritonavir and darunavir/ritonavir.
    • (2011) J Clin Pharmacol , vol.51 , pp. 237-242
    • Song, I.1    Min, S.S.2    Borland, J.3
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    • Effect of atazanavir and atazanavir/ritonavir on the pharmacokinetics of the next-generation HIV integrase inhibitor,S/GSK1349572
    • Although the investigators observed significant increases in dolutegravir exosurewith atazanavir and atazanavir/ritonavir likely due to UGT inhibition they concludethat these changes are unlikely to negatively imact theray
    • Song I, Borland J, Chen S, et al. Effect of atazanavir and atazanavir/ritonavir on the pharmacokinetics of the next-generation HIV integrase inhibitor,S/GSK1349572. Br J Clin Pharmacol 2011; 72:103-108. Although the investigators observed significant increases in dolutegravir exposurewith atazanavir and atazanavir/ritonavir, likely due to UGT inhibition, they concludethat these changes are unlikely to negatively impact therapy.
    • (2011) Br J Clin Pharmacol , Issue.72 , pp. 103-108
    • Song, I.1    Borland, J.2    Chen, S.3
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    • Safety, tolerability, and pharmacokinetics ofthe HIV integrase inhibitor dolutegravir given twice daily with rifampin: Resultsof a Phase I study among healthy subjects
    • March 5-8, 2012; Seattle, WA. Paper #148.This abstract provides evidence for increased dolutegravir dosing frequency whenadministered with rifampin
    • Dooley KE, Purdy E, Sayre P, et al. Safety, tolerability, and pharmacokinetics ofthe HIV integrase inhibitor dolutegravir given twice daily with rifampin: resultsof a Phase I study among healthy subjects. 19th Conference on Retrovirusesand Opportunistic Infections; March 5-8, 2012; Seattle, WA. Paper #148.This abstract provides evidence for increased dolutegravir dosing frequency whenadministered with rifampin.
    • 19th Conference on Retrovirusesand Opportunistic Infections
    • Dooley, K.E.1    Purdy, E.2    Sayre, P.3
  • 54
    • 84872668667 scopus 로고    scopus 로고
    • Pharmacokinetics, safety, and tolerability of the HIV integrase inhibitor dolutegravir co-administered with rifabutin inhealthy subjects
    • April 2012; Barcelona, Spain. Abstract P/11.Rifabutin can be co-administered with dolutegravir without dose adjustment,despite a 30% decrease in dolutegravir trough concentration
    • Dooley KE, Sayre P, Borland J, et al. Pharmacokinetics, safety, and tolerability of the HIV integrase inhibitor dolutegravir co-administered with rifabutin inhealthy subjects. 13th International Workshop on Clinical Pharmacology ofHIV Therapy; April 16-18, 2012; Barcelona, Spain. Abstract P/11.Rifabutin can be co-administered with dolutegravir without dose adjustment,despite a 30% decrease in dolutegravir trough concentration.
    • 13th International Workshop on Clinical Pharmacology ofHIV Therapy , pp. 16-18
    • Dooley, K.E.1    Sayre, P.2    Borland, J.3
  • 55
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    • Pharmacokinetics of the HIV integraseinhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers
    • This article highlights the clinically important interaction between antacids anddolutegravir
    • Patel P, Song I, Borland J, et al. Pharmacokinetics of the HIV integraseinhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. J Antimicrob Chemother 2011; 66:1567-1572.This article highlights the clinically important interaction between antacids anddolutegravir.
    • (2011) J Antimicrob Chemother , vol.66 , pp. 1567-1572
    • Patel, P.1    Song, I.2    Borland, J.3
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    • Clinical pharmacology of the hiv integrase inhibitor elvitegravir
    • October 24-27, 2007; Madrid, Spain. Abstract PS4/7
    • Ramanathan S, Mathias AA, Hinkle J, Kearney BP. Clinical pharmacology of the HIV integrase inhibitor elvitegravir. 11th European AIDS Conference; October 24-27, 2007; Madrid, Spain. Abstract PS4/7.
    • 11th European AIDS Conference
    • Ramanathan, S.1    Mathias, A.A.2    Hinkle, J.3    Kearney, B.P.4
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    • Week 48 results of an ongoing phase 3 study comparing elvitegravir/cobicistat/emtricitabine/tenofovir (Quad) with atazanavir/ritonavir plus emtricitabine/tenofovir in treatment-naíve HIV-1 subjects showing efficacy, safety, and pharmacokinetics
    • March 5-8, 2012; Seattle, WA. Paper #627
    • DeJesus E, Rockstroh J, Henry K, et al. Week 48 results of an ongoing phase 3 study comparing elvitegravir/cobicistat/emtricitabine/tenofovir (Quad) with atazanavir/ritonavir plus emtricitabine/tenofovir in treatment-naíve HIV-1; subjects showing efficacy, safety, and pharmacokinetics. 19th Conference on Retroviruses and Opportunistic Infections; March 5-8, 2012; Seattle, WA. Paper #627.
    • 19th Conference on Retroviruses and Opportunistic Infections
    • DeJesus, E.1    Rockstroh, J.2    Henry, K.3
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    • 84863816714 scopus 로고    scopus 로고
    • Elvitegravir/cobicistat/emtricitabine/tenofovir (Quad) has noninferior efficacy and favorable safety compared to efavirenz/ emtricitabine/tenofovir in treatment-naíve HIV-1 subjects
    • March 5-8, 2012; Seattle, WA. Paper #101
    • Sax P, DeJesus E, Millis A, et al. Elvitegravir/cobicistat/emtricitabine/ tenofovir (Quad) has noninferior efficacy and favorable safety compared to efavirenz/ emtricitabine/tenofovir in treatment-naíve HIV-1; subjects. 19th Conference on Retroviruses and Opportunistic Infections; March 5-8, 2012; Seattle, WA. Paper #101.
    • 19th Conference on Retroviruses and Opportunistic Infections
    • Sax, P.1    DeJesus, E.2    Millis, A.3
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    • 84155164041 scopus 로고    scopus 로고
    • Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: Randomised, doubleblind, phase 3, noninferiority study
    • This hase 3 clinical trial evaluates the safety and efficacy of once-daily ritonavirboosted elvitegravir with raltegravir as an active comarator
    • Molina JM, Lamarca A, Andrade-Villanueva J, et al. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, doubleblind, phase 3, noninferiority study. Lancet Infect Dis 2012; 12:27-35. This phase 3 clinical trial evaluates the safety and efficacy of once-daily ritonavirboosted elvitegravir with raltegravir as an active comparator.
    • (2012) Lancet Infect Dis , Issue.12 , pp. 27-35
    • Molina, J.M.1    Lamarca, A.2    Andrade-Villanueva, J.3
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    • Dolutegravir (DTG, s/GSK1349572) treatment of subjects with raltegravir (RAL) resistance: viral suppression at week 24 inVIKING study
    • October 12-15,; Belgrade, Serbia. Abstract PS1/2
    • Soriano V, Cox J, Eron JJ, et al. Dolutegravir (DTG, s/GSK1349572) treatment of subjects with raltegravir (RAL) resistance: viral suppression at week 24 inVIKING study. 13th European AIDS Conference; October 12-15, 2011; Belgrade, Serbia. Abstract PS1/2.
    • (2011) 13th European AIDS Conference
    • Soriano, V.1    Cox, J.2    Eron, J.J.3
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    • Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: Planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial
    • This hase 3 clinical trial rovides evidence for the efficacy and safety of dolutegravir in treatment-naíve atients
    • van Lunzen J, Maggiolo F, Arribas JR, et al. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. Lancet Infect Dis 2012; 12:111-118. This phase 3 clinical trial provides evidence for the efficacy and safety of dolutegravir in treatment-naíve patients.
    • (2012) Lancet Infect Dis , Issue.12 , pp. 111-118
    • Van Lunzen, J.1    Maggiolo, F.2    Arribas, J.R.3
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    • DTG in subjects with hiv exhibiting ral resistance: functional monotherapy results of VIKING study cohort II
    • Feb 27-Mar 2 2011; Boston, MA. Paper #151LB
    • Eron JJ, Kumar P, Lazzarin A, et al. DTG in subjects with HIV exhibiting RAL resistance: Functional monotherapy results of VIKING study cohort II. 18th Conference on Retroviruses and Opportunistic Infections; Feb 27-Mar 2, 2011; Boston, MA. Paper #151LB
    • 18th Conference on Retroviruses and Opportunistic Infections
    • Eron, J.J.1    Kumar, P.2    Lazzarin, A.3
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    • Dolutegravir in combination therapy exhibits rapid and sustained antiviral response in ARV-naive adults: 96-week results from SPRING-1 (ING112276)
    • March 5-8, 2012; Seattle, WA. Paper #102LB
    • Stellbrink HJ, Reynes J, Lazzarin A, et al. Dolutegravir in combination therapy exhibits rapid and sustained antiviral response in ARV-naive adults: 96-week results from SPRING-1 (ING112276). 19th Conference on Retroviruses and Opportunistic Infections; March 5-8, 2012; Seattle, WA. Paper #102LB.
    • 19th Conference on Retroviruses and Opportunistic Infections
    • Stellbrink, H.J.1    Reynes, J.2    Lazzarin, A.3
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    • Pharmacokinetics of a dolutegravir pediatric granule formulation in healthy adult subjects
    • March 5-8, 2012; Seattle, WA. Paper #985
    • Patel P, Song I, Borland J, et al. Pharmacokinetics of a dolutegravir pediatric granule formulation in healthy adult subjects. 19th Conference on Retroviruses and Opportunistic Infections; March 5-8, 2012; Seattle, WA. Paper #985.
    • 19th Conference on Retroviruses and Opportunistic Infections
    • Patel, P.1    Song, I.2    Borland, J.3
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