Role of raltegravir in HIV-1 management;El Papel de Raltegravir en el Manejo de IVH-1

Annals of Pharmacotherapy

Volumn 46, Issue 4, 2012, Pages 578-589

  Rokas, Kristina E E ^a   Brandon Bookstaver, P ^a   Shamroe, Caitlin L ^a   Scott Sutton, S ^a   Millisor, Vanessa E ^a   Bryant, Jacquelyn E ^a   Weissman, Sharon B ^b  

^a UNIVERSITY OF SOUTH CAROLINA   (United States)

^b UNIVERSITY OF SOUTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Antiretroviral therapy; Integrase strand transfer inhibitor; MK 0518; Raltegravir; Treatment na ve

Indexed keywords

ABACAVIR PLUS LAMIVUDINE; ATAZANAVIR; ATAZANAVIR PLUS RITONAVIR; DARUNAVIR; DOLUTEGRAVIR; EFAVIRENZ; EFAVIRENZ PLUS EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; ELVITEGRAVIR; EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; ETRAVIRINE; LOPINAVIR PLUS RITONAVIR; OMEPRAZOLE; RALTEGRAVIR; RIFABUTIN; RIFAMPICIN; TENOFOVIR; VIRUS RNA;

AMINOTRANSFERASE BLOOD LEVEL; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; BILIRUBIN BLOOD LEVEL; CENTRAL NERVOUS SYSTEM DISEASE; CHOLESTEROL BLOOD LEVEL; COMBINATION CHEMOTHERAPY; CREATINE KINASE BLOOD LEVEL; DIZZINESS; DRUG ABSORPTION; DRUG ANTAGONISM; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG METABOLISM; DRUG POTENCY; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; GASTROENTERITIS; GASTROINTESTINAL SYMPTOM; GLUCURONIDATION; HEADACHE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; IC 50; LUNG EMBOLISM; MAXIMUM PLASMA CONCENTRATION; MEDLINE; PRIORITY JOURNAL; RASH; REVIEW; SIDE EFFECT; STEADY STATE; STEVENS JOHNSON SYNDROME; TOXIC EPIDERMAL NECROLYSIS; TREATMENT WITHDRAWAL; TRIACYLGLYCEROL BLOOD LEVEL; VIRUS LOAD;

ADENINE; ANIMALS; ANTI-HIV AGENTS; DEOXYCYTIDINE; DRUG THERAPY, COMBINATION; HIV INFECTIONS; HIV INTEGRASE INHIBITORS; HIV-1; HUMANS; PHOSPHONIC ACIDS; PYRROLIDINONES;

EID: 84859724580     PISSN: 10600280     EISSN: None     Source Type: Journal    
DOI: 10.1345/aph.1Q616     Document Type: Review

References (101)

1. vanSighem AI, Gras LA, Reiss P, Brinkman K, de Wolf F. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. AIDS 2010;24:1527-35. DOI 10.1097/QAD.0b013e32833a3946
2. Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services, October 14, 2011:1-167. www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf (accessed 2011 Dec 14).
3. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011;365:493-505. DOI 10.1056/NEJMoa1105243
4. Zolopa A, Andersen J, Powderly W, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS One 2009;4: e5575. DOI 10.1371/journal.pone.0005575
5. Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009;360: 1815-26. DOI 10.1056/NEJMoa0807252
6. Siegfried N, van der Merwe L, Brocklehurst P, Sint TT. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev 2011;CD003510. DOI 10.1002/14651858.CD003510.pub3
7. Muga R, Ferreros I, Langohr K, et al. Changes in the incidence of tuberculosis in a cohort of HIV-seroconverters before and after the introduction of HAART. AIDS 2007;21:2521-7. DOI 10.1097/QAD.0b013e3282f1c933
8. Product information. Isentress (raltegravir). Whitehouse Station, NJ: Merck & Co., Inc., November 2011.
9. Grinsztejn B, Nguyen BY, Katlama C, et al. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet 2007;369:1261-9. DOI 10.1016/S0140-6736(07)60597-2
10. Gatell JM, Katlama C, Grinsztejn B, et al. Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a Phase II study. J Acquir Immune Defic Syndr 2010;50: 605-12. DOI 10.1097/QAI.0b013e3181c9c967
11. Lennox JL, Dejesus E, Berger DS, et al. Raltegravir versus efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. J Acquir Immune Defic Syndr 2010;55:39-48. DOI 10.1097/QAI.0b013e3181da1287
12. Lennox JL, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatmentnaïve patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet 2009;374:796-806. DOI 10.1016/S0140-6736(09)60918-1
13. Young B, Vanig T, DeJesus E, et al. 96-Week results of a pilot study of abacavir/lamivudine and raltegravir in antiretroviral-naïve HIV-1 infected patients: the SHIELD trial. HIV Clin Trials 2011;12:228-33. DOI 10.1310/HCT1204-228
14. Markowitz M, Nguyen BY, Gotuzzo E, et al. Rapid and durable antiretroviral effect of the HIV-1 integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr 2007;4:125-33. DOI 10.1097/QAI.0b013e318157131c
15. Marinello J, Marchand C, Mott BT, et al. Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Biochemistry 2008;47:9345-54. DOI 10.1021/bi800791q
16. Mathias AA, West S, Hui J, Kearney BP. Dose-response of ritonavir on hepatic CYP3A activity and elvitegravir oral exposure. Clin Pharmacol Ther 2009;85:64-70. DOI 10.1038/clpt.2008.168
17. DeJesus E, Berger D, Markowitz M, et al. Antiviral activity, pharmacokinetics, and dose response of the HIV-1 integrase inhibitor GS-9137 (JTK-303) in treatment-naive and treatment-experienced patients. J Acquir Immune Defic Syndr 2006;43:1-5. DOI 10.1097/01.qai.0000233308.82860.2f
18. German P, Warren D, West S, Hui J, Kearney BP. Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancer-containing single-tablet fixed-dose combination regimen for the treatment of HIV. J Acquir Immune Defic Syndr 2010;55:323-9. DOI 10.1097./QAI.0b013e3181eb376b
19. Min S, Song I, Borland J, et al. Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Antimicrob Agents Chemother 2010;54:254-8. DOI 10.1128/AAC.00842-09
20. Kobayashi M, Yoshinaga T, Seki T, et al. In vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother 2011;55:813-21. DOI 10.1128/AAC.01209-10
21. Hightower KE, Wang R, Deanda F, et al. Dolutegravir (S/GSK1349572) exhibits significantly slower dissociation than raltegravir and elvitegravir from wild-type and integrase inhibitor-resistant HIV-1 integrase-DNA complexes. Antimicrob Agents Chemother 2011;55:4552-9. DOI 10.1128/AAC.00157-11
22. Iwamoto M, Wenning LA, Petry AS, et al. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin Pharmacol Ther 2008;83:293-9. DOI 10.1038/sj.clpt.6100281
23. Merck new drug approval form. Isentress (raltegravir). Whitehouse Station, NJ: Merck & Co., Inc., August 2007.
24. Calcagno A, Bonora S, D'Avolio A, et al. Raltegravir penetration in seminal plasma of healthy volunteers. Antimicrob Agents Chemother 2010;54:2744-5. DOI 10.1128/AAC.00241-10
25. Clavel C, Peytavin G, Tubiana R, et al. Raltegravir concentrations in the genital tract of HIV-1-infected women treated with a raltegravir-containing regimen (DIVA 01 study). Antimicrob Agents Chemother 2011;55: 3018-21. DOI 10.1128/AAC.01460-10
26. Jones AE, Talameh JA, Patterson KB, et al. First-dose and steady-state pharmacokinetics of raltegravir in the genital tract of HIV negative women. Presented at: the 10th International Workshop on Clinical Pharmacology of HIV Therapy, Amsterdam, Netherlands, April 15-May 1, 2009.
27. Chan DJ. Pathophysiology of HIV-1 in semen: current evidence for compartmentalisation and penetration by antiretroviral drugs. Curr HIV Res 2005;3:207-22. DOI 10.2174/1570162054368039
28. Yilmaz A, Gisslén M, Spudich S, et al. Raltegravir cerebrospinal fluid concentrations in HIV-1 infection. PLoS One 2009;4:e6877. DOI 10.1371/journal.pone.0006877
29. Croteau D, Letendre S, Best BM, et al. Total raltegravir concentrations in cerebrospinal fluid exceed the 50-percent inhibitory concentration for wild-type HIV-1. Antimicrob Agents Chemother 2010;54:5156-60. DOI 10.1128/AAC.00507-10
30. Dahl V, Lee E, Peterson J, et al. Raltegravir treatment intensification does not alter cerebrospinal fluid HIV-1 infection or immunoactivation in subjects on suppressive therapy. J Infect Dis 2011;204:1936-45. DOI 10.1093/infdis/jir667
31. Blouin RA, Kolpek JH, Mann HJ. Influence of obesity on drug disposition. Clin Pharm 1987;6:706-14.
32. Blouin RA, Chandler MHH. Applied pharmacokinetics: principles of therapeutic drug monitoring. In: Evans WE, Schentag JJ, Jusko WJ, et al, eds. Applied Therapeutics. 3rd ed. Vancouver, BC, Canada: Applied therapeutics Inc., 1992:11.3-11.20.
33. Squires K, Bekker L, Eron J, et al (REALMRK Investigators). Safety, tolerability, and efficacy of raltegravir (RAL) in a diverse cohort of HIVinfected patients (pts): 48-week results from the REALMRK study (abstract H2-789). Presented at: the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, September 17-20, 2011.
34. Iwamoto M, Hanley WD, Petry AS, et al. Lack of a clinically important effect of moderate hepatic insufficiency and severe renal insufficiency on raltegravir pharmacokinetics. Antimicrob Agents Chemother 2009;53: 1747-52. DOI 10.1128/AAC.01194-08
35. Hluhanich R, Kinkade A, Wang M, et al. HIV integrase inhibitors do not exert a post-antibiotic effect despite slow dissociation from integrase-DNA complexes in vitro (abstract H-930). Presented at: the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, September 12-15, 2009.
36. Lanzafarme M, Hill A, Lattuada E, et al. Raltegravir: is a 400 mg once daily dose enough? J Antimicrob Chemother 2010;65:595-7. DOI 10.1093/jac/dkp488
37. Vispo E, Barreiro P, Maida I, et al. Simplification from protease inhibitors to once-or twice-daily raltegravir: the ODIS trial. HIV Clin Trials 2010;11: 197-204. DOI 10.1310/hct1104-197
38. Eron JJ, Rockstroh JK, Reynes J, et al. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, activecontrolled, phase 3 non-inferiority trial. Lancet Infect Dis 2011;11:907-15. DOI 10.1016/S1473-3099(11)70196-7
39. Thompson MA, Aberg JA, Cahn P, et al. Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel. JAMA 2010;304:321-33. DOI 10.1001/jama.2010.1004
40. Gotuzzo E, Nguyen B, Markowitz M, et al. Sustained efficacy and tolerability of raltegravir after 240 weeks of combination ART in treatmentnaïve HIV-1 infected patients; final analysis of protocol 004 (abstract WEPDB0102). Presented at: the 6th International AIDS Society, Rome, Italy, July 17-20, 2011.
41. Rockstroh JK, Lennox JL, DeJesus E, et al. Long-term treatment with raltegravir or efavirenz combined with tenofovir/emtricitabine for treatment-naive human immunodeficiency virus-1-infected patients: 156-week results from STARTMRK. Clin Infect Dis 2011;53:807-16. DOI 10.1093/cid/cir510
42. Taiwo B, Zheng L, Gallien S, et al. Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naïve HIV-1-infected patients (ACTG A5262). AIDS 2011;25:2113-22.
43. Bedimo R, Drechsler H, Turner D, et al. RADAR study: raltegravir combined with boosted darunavir has similar safety and antiviral efficacy as tenofovir/emtricitabine combined with boosted darunavir in antiretroviral-naïve patients (abstract MOPE214). Presented at: the 6th International AIDS Society, Rome, Italy, July 17-20, 2011.
44. Reynes J, Lawal A, Pulido F, et al. Examination of noninferiority, safety, and tolerability of lopinavir/ritonavir and raltegravir compared with lopinavir/ritonavir and tenofovir/ emtricitabine in antiretroviral-naïve subjects: the progress study, 48-week results. HIV Clin Trials 2011;12:255-67. DOI 10.1310/hct1205-255
45. Gathe J, Reynes J, Pulido F, et al. Lopinavir/ritonavir (LPV/r) combined with raltegravir (RAL) or tenofovir/emtricitabine (TDF/FTC) in antiretroviral-naïve subjects: 96-week efficacy and safety results of the PROGRESS study (abstract 406). Presented at: the Infectious Disease Society of America, Boston, MA, October 20-23, 2011.
46. Bowman V, Rieg G, Jain S, et al. 48 week results of a pilot randomized study of a nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimen of raltegravir (RAL) + lopinavir/ritonavir (LPV/r) versus efavirenz/ tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) in antiretro (abstract CDB336). Presented at: the 6th International AIDS Society, Rome, Italy, July 17-20, 2011.
47. Kozal MJ, Lupo S, DeJesus E, et al. The SPARTAN study: a pilot study to assess the safety and efficacy of an investigational NRTI-and RTVsparing regimen of atazanavir (ATV) experimental dose of 300 mg BID plus raltegravir (RAL) 400 mg BID (ATV+RAL) in treatment-naïve HIV-infected subjects (abstract THLBB204). Presented at: the International AIDS Conference, Vienna, Austria, July 18-23, 2010.
48. Fabbiani M, Di Giambenedetto S, Ragazzoni E, et al. Darunavir/ritonavir and raltegravir coadministered in routine clinical practice: potential role for an unexpected drug interaction. Pharmacol Res 2011;63:249-53. DOI 10.1016/j.phrs.2010.11.009
49. Boffito M, Moyle G, Hill A, et al. The pharmacokinetic profile of darunavir with low-dose ritonavir (DRV/r) in various multiple-dose regimens over 120 hours (abstract P31). Presented at: the 9th International Workshop on Clinical Pharmacology of HIV Therapy, New Orleans, LA, April 7-9, 2008.
50. ClinicalTrials. gov. An open-label randomised two-year trial comparing two first-line regimens in HIV-infected antiretroviral naïve subjects: darunavir/r + tenofovir/emtricitabine vs. darunavir/r + raltegravir (ANRS 143/NEAT 001). http://clinicaltrials.gov/ct2/show/NCT01066962 (accessed 2012 Mar 30).
51. Ceccherini-Silberstein F, Malet I, Fabeni L, et al. Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviraltreated HIV-1-infected patients, all naive to integrase inhibitors. J Antimicrob Chemother 2010;65:2305-18. DOI 10.1093/jac/dkq326
52. Steigbigel RT, Cooper DA, Kumar PN, et al. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med 2008;359:339-54. DOI 10.1056/NEJMoa0708975
53. Steigbigel RT, Cooper DA, Teppler H, et al. Long-term efficacy and safety of raltegravir combined with optimized background therapy in treatment experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials. Clin Infect Dis 2010;50:605-12. DOI 10.1086/650002
54. Gallien S, Braun J, Delaugerre C, et al. Efficacy and safety of raltegravir in treatment-experienced HIV-1-infected patients switching from enfuvirtidebased regimens: 48 week results of the randomized EASIER ANRS 138 trial. J Antimicrob Chemother 2011;66:2099-106. DOI 10.1093/jac/dkr269
55. Eron JJ, Young B, Cooper DA, et al. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet 2010;375:396-407. DOI 10.1016/S0140-6736(09)62041-9
56. Martinez E, Larrousse M, Lilbre JM, et al. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS 2010;24:1697-707. DOI 10.1097/QAD.0b013e32833a608a
57. Nguyen A, Calmy A, Delhumeau C, et al. A randomized cross-over study to compare raltegravir and efavirenz (SWITCH-ER study). AIDS 2011;25:1481-7. DOI 10.1097/QAD.0b013e328348dab0
58. Towner W, Klein D, Kerrigan HL, et al. Virologic outcomes of changing enfuvirtide to raltegravir in HIV-1 patients well controlled on an enfuvirtide based regimen: 24-week results of the CHEER study. J Acquir Immune Defic Syndr 2009;51:367-73. DOI 10.1097/QAI.0b013e3181ae35de
59. Towner W, Lalezari J, Sension MG, et al. Efficacy, safety, and tolerability of etravirine with and without darunavir/ritonavir or raltegravir in treatment experienced patients: analysis of the etravirine early access program in the United States. J Acquir Immune Defic Syndr 2010;53:614-8. DOI 10.1097/QAI.0b013e3181cdebb1
60. Boulet T, Pavie J, Charreau I, et al. Impact on health-related quality of life of a switch from enfuvirtide to raltegravir among multidrug-resistant HIV-1-infected patients: a randomized open-label trial (EASIER-ANRS 138). HIV Clin Trials 2010;11:283-93. DOI 10.1310/hct1105-283
61. Skiest DJ, Cohen C, Mounzer K, et al. Similar efficacy of raltegravir when used with or without a protease inhibitor in treatment-experienced patients. HIV Clin Trials 2011;12:131-40. DOI 10.1310/hct1203-131
62. Rosenblum M, Deeks SG, van der Laan M, Bangsberg DR. The risk of virologic failure decreases with duration of HIV suppression, at greater than 50% adherence to antiretroviral therapy. PloS ONE 2009;4:e7196. DOI 10.1371/journal.pone.0007196
63. Markowitz M, Morales-Ramirez JO, Nguyen BY, et al. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naïve HIV-1-infected individuals. J Acquir Immune Defic Syndr 2006;43:509-15. DOI 10.1097/QAI.0b013e31802b4956
64. Samaras K, Richardson R, Carr A. Postprandial lipid effects of low-dose ritonavir vs raltegravir in HIV-uninfected adults. AIDS 2010;24:1727-31. DOI 10.1097/QAD.0b013e32833ac7be
65. Dori L, Buonomini AR, Viscione M, Sarmati L, Andreoni M. A case of rhabdomyolysis associated with raltegravir use. AIDS 2010;24:473-5. DOI 10.1097/QAD.0b013e328334cc4a
66. Masiá M, Enríquez R, Sirvent A, Gutiérrez F. Severe acute renal failure associated with rhabdomyolysis during treatment with raltegravir. A call for caution. J Infect 2010;61:189-90. DOI 10.1016/j.jinf.2010.04.011
67. Zembower TR, Gerzenshtein L, Coleman K, Palella FJ Jr. Severe rhabdomyolysis associated with raltegravir use. AIDS 2008;22:1382-4. DOI 10.1097/QAD.0b013e328303be40
68. Rockstroh J, Teppler H, Zhao J, et al. Safety and efficacy of raltegravir in patients with HIV-1 and hepatitis B and/or C virus coinfection. HIV Med 2012;13:127-31. DOI 10.1111/j.1468-1293.2011.00933.x
69. Kassahun K, McIntosh I, Cui D, et al. Metabolism and disposition in humans of raltegravir (MK-0518), an anti-AIDS drug targeting the human immunodeficiency virus 1 integrase enzyme. Drug Metab Dispos 2007;35:1657-63. DOI 10.1124/dmd.107.016196
70. Wenning LA, Hanley WD, Brainard DM, et al. Effect of rifampin, a potent inducer of drug-metabolizing enzymes, on the pharmacokinetics of raltegravir. Antimicrob Agents Chemother 2009;53:2852-6. DOI 10.1128/AAC.01468-08
71. Brainard DM, Kassahun K, Wenning LA, et al. Lack of a clinically meaningful pharmacokinetic effect of rifabutin on raltegravir: in vitro/in vivo correlation. J Clin Pharmacol 2011;51:943-50. DOI 10.1177/0091270010375959
72. Neely M, Decosterd L, Fayet A, et al. Pharmacokinetics and pharmacogenomics of once-daily raltegravir and atazanavir in healthy volunteers. Antimicrob Agents Chemother 2010;54:4619-25. DOI 10.1128/AAC.00712-10
73. Iwamoto M, Wenning LA, Mistry GC, et al. Atazanavir modestly increases plasma levels of raltegravir in healthy subjects. Clin Infect Dis 2008;47:137-40. DOI 10.1086/588794
74. Wenning LA, Friedman EJ, Kost JT, et al. Lack of a significant drug interaction between raltegravir and tenofovir. Antimicrob Agents Chemother 2008;52:3253-8. DOI 10.1128/AAC.00005-08
75. Hanley WD, Wenning LA, Moreau A, et al. Effect of tipranavir-ritonavir on pharmacokinetics of raltegravir. Antimicrob Agents Chemother 2009;53:2752-5. DOI 10.1128/AAC.01486-08
76. Garvey L, Latch N, Erlwein OW, et al. The effects of a nucleoside-sparing antiretroviral regimen on the pharmacokinetics of ritonavir-boosted darunavir in HIV type-1-infected patients. Antivir Ther 2010;15:213-8. DOI 10.3851/IMP1517
77. Goldwirt L, Braun J, de Castro N, et al. Switch from enfuvirtide to raltegravir lowers plasma concentrations of darunavir and tipranavir: a pharmacokinetic substudy of the EASIER-ANRS 138 trial. Antimicrob Agents Chemother 2011;55:3613-5. DOI 10.1128/AAC.01827-10
78. Anderson MS, Kakuda TN, Hanley W, et al. Minimal pharmacokinetic interaction between the human immunodeficiency virus nonnucleoside reverse transcriptase inhibitor etravirine and the integrase inhibitor raltegravir in healthy subjects. Antimicrob Agents Chemother 2008;52:4228-32. DOI 10.1128/AAC.00487-08
79. Ménard A, Solas C, Mokthari S, et al. Etravirine-raltegravir, a marked interaction in HIV-1-infected patients: about four cases. AIDS 2009;23: 869-71. DOI 10.1097/QAD.0b013e328329915f.
80. Do VT, Higginson RT, Fulco PP. Raltegravir dosage adjustment in HIVinfected patients receiving etravirine. Am J Health Syst Pharm 2011;68: 2049-54. DOI 10.2146/ajhp110083
81. Iwamoto M, Wenning LA, Nguyen BY, et al. Effects of omeprazole on plasma levels of raltegravir. Clin Infect Dis 2009;48:489-92. DOI 10.1086/596503
82. Kiser JJ, Bumpass JB, Meditz AL, et al. Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus-seronegative volunteers. Antimicrob Agents Chemother 2010;54:4999-5003. DOI 10.1128/AAC.00636-10
83. Roberts JL, Kiser JJ, Hindman JT, Meditz AL. Virological failure with a raltegravir-containing antiretroviral regimen and concomitant calcium administration: case report. Pharmacotherapy 2011;31:298e-302e.
84. Métifiot M, Marchand C, Maddali K, Pommier Y. Resistance to integrase inhibitors. Viruses 2010;2:1347-66. DOI 10.3390/v2071347
85. Fransen S, Gupta S, Danovich R, et al. Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. J Virol 2009;83:11440-6. DOI 10:1128/JVI.01168-09
86. Delelis O, Malet I, Na L, et al. The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Nucleic Acids Res 2009;37:1193-201. DOI 10.1093/nar/gkn1050
87. Wirden M, Simon A, Schneider L, et al. Raltegravir has no residual antiviral activity in vivo against HIV-1 with resistance-associated mutations to this drug. J Antimicrob Chemother 2009;64:1087-90. DOI 10:1093/jac/dkp310
88. Baldanti F, Paolucci S, Gulminetti R, et al. Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens. J Med Virol 2010;82:116-22. DOI 10.1002/jmv.21651
89. Paar C, Palmetshofer C, Flieger K, et al. Genotypic antiretroviral resistance testing for human immunodeficiency virus type 1 integrase inhibitors by use of the TruGene sequencing system. J Clin Microbiol 2008;46:4087-90. DOI 10.1128/JCM.01246-08
90. Ceccherini-Silberstein F, Van Baelen K, Armenia D, et al. Secondary integrase resistance mutations found in HIV-1 minority quasispecies in integrase therapy-naive patients have little or no effect on susceptibility to integrase inhibitors. Antimicrob Agents Chemother 2010;54:3938-48. DOI 10.1128/AAC.01720-09
91. Varghese V, Liu TF, Rhee SY, et al. HIV-1 integrase sequence variability in antiretroviral naïve patients and in triple-class experienced patients subsequently treated with raltegravir. AIDS Res Hum Retroviruses 2010;26:1323-6. DOI 10.1089/aid.2010.0123
92. Molina JM, Lamarca A, Andrade-Villanueva J, et al. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatmentexperienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect Dis 2012;12:27-35. DOI 10.1016/S1473-3099(11)70249-3
93. Cohen C, Elion R, Ruane P, et al. Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection. AIDS 2011;25:F7-12. DOI 10.1097/QAD.0b013e328345766f
94. Sax P, DeJesus E, Mills A, et al. Elvitegravir/cobicistat/emtricitabine/ tenofovir (Quad) has non-inferior efficacy and favorable safety compared to efavirenz/emtricitabine/tenofovir in treatment-naïve HIV-1+ subjects (abstract 101). Presented at: the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, March 5-8, 2012.
95. DeJesus E, Rockstroh J, Henry K, et al. Week 48 results of an ongoing global phase 3 study comparing elvitegravir/cobicistat/emtricitabine/ tenofovir (Quad) with atazanavir/ritonavir plus emtricitabine/tenofovir in treatment-naïve HIV-1+ subjects showing efficacy, safety, and pharmacokinetics (abstract 627). Presented at: the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, March 5-8,2012.
96. Molina JM, Lamarca A, Andrade-Villanueva J, et al. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatmentexperienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect Dis 2012;12:27-35. DOI 10.1016/S1473-3099(11)70249-3
97. Eron J, Kumar P, Lazzarin A, et al. DTG in subjects with HIV exhibiting RAL resistance: functional monotherapy results of VIKING study cohort II (abstract 151LB). Presented at: the 18th Conference on Retroviruses and Opportunistic Infections, Boston, MA, February 27-March 2, 2011.
98. Min S, Carrod A, Curtis L, et al. Safety profile of dolutegravir (DTG, S/GSK1349572), in combination with other antiretrovirals in antiretroviral (ART)-naive and ART-experienced adults from two phase IIb studies (abstract TUPE238). Presented at: the 6th International AIDS Society, Rome, Italy, July 17-20, 2011.
99. Elion R, Cohen C, Gathe J, et al. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/ tenofovir in the initial treatment of HIV infection. AIDS 2011;25: 1881-6. DOI 10.1097/QAD.0b013e32834b4d48
100. Métifiot M, Johnson B, Smith S, et al. MK-0536 inhibits HIV-1 integrases resistant to raltegravir. Antimicrob Agents Chemother 2011;55:5127-33. DOI 10.1128/AAC.05288-11
101. Fenwick C, Bethell R, Quinson A, et al. BI 224436, a non-catalytic site integrase inhibitor is a potent inhibitor of the replication of treatmentnaïve and raltegravir-resistant clinical isolates of HIV-1 (abstract F1-1370). Presented at: the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, September 17-20, 2011.