Review of the safety, efficacy, and pharmacokinetics of elvitegravir with an emphasis on resource-limited settings

HIV/AIDS - Research and Palliative Care

Volumn 4, Issue , 2012, Pages 5-15

  Lee, Janice Soo Fern ^a   Calmy, Alexandra ^a   Andrieux Meyer, Isabelle ^a   Ford, Nathan ^a,b  

^a GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^b UNIVERSITY OF CAPE TOWN   (South Africa)

Author keywords

Efficacy; Elvitegravir; Resistance; Resource limited settings; Safety

Indexed keywords

ABACAVIR; ANTACID AGENT; ATAZANAVIR; ATAZANAVIR PLUS RITONAVIR; COBICISTAT; DARUNAVIR PLUS RITONAVIR; DIDANOSINE; EFAVIRENZ PLUS EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; ELVITEGRAVIR; EMTRICITABINE; ETHINYLESTRADIOL; ETHINYLESTRADIOL PLUS NORGESTIMATE; ETRAVIRINE; FOSAMPRENAVIR; FOSAMPRENAVIR PLUS RITONAVIR; KETOCONAZOLE; LOPINAVIR; LOPINAVIR PLUS RITONAVIR; MARAVIROC; OMEPRAZOLE; PLACEBO; RIFABUTIN; RIFAMPICIN; RITONAVIR; RITONAVIR PLUS TIPRANAVIR; STAVUDINE; TENOFOVIR; TIPRANAVIR; UNINDEXED DRUG; ZIDOVUDINE;

ABNORMAL DREAMING; ABNORMAL LABORATORY RESULT; ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; CREATININE BLOOD LEVEL; DIARRHEA; DIZZINESS; DRUG ABSORPTION; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENTIATION; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; FATIGUE; GLOMERULUS FILTRATION RATE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; KIDNEY FUNCTION; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NEUTROPENIA; NIGHTMARE; NONHUMAN; REVIEW; SIDE EFFECT; SOMNOLENCE; SYSTEMATIC REVIEW; VIRUS INHIBITION; VIRUS REPLICATION; VOMITING;

EID: 84863116362     PISSN: None     EISSN: 11791373     Source Type: Journal    
DOI: None     Document Type: Review

References (51)

1. Clayden P, Collins S, Harrington M, et al. HIV, Hepatitis C Virus (HCV), and tuberculosis drugs, diagnostics, vaccines, and preventive technologies in development. 2011 pipeline report second edition. i-Base/Treatment Action Group, New York; 2011.
2. Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Rockville, MD: DHHS; 2011 [upated November 29]. Available from: http://aidsinfo.nih.gov/Guidelines/HTML/1/adultand-adolescent-treatment-guidelines/1/panel-roster/. Accessed November 30, 2011.
3. Global HIV/AIDS response: epidemic update and health sector progress towards Universal Access. Geneva: WHO/UNAIDS; 2011. Available from: http://www.who.int/hiv/pub/progress_report2011/hiv_full_report_2011.pdf. Accessed December 28, 2011.
4. Renaud-Théry F, Duncombe C, Kerr S, Thierry S, Perriëns J. Adult ART in resource-limited settings: a systematic review of first-line treatment failure and attrition rates. 17th Conference on Retroviruses and Opportunities Infections, San Francisco, February 16-20, 2010. Paper 827.
5. El-Khatib Z, Ekstrom AM, Ledwaba J, Mohapi L, Laher F, Karstaedt A, et al. Viremia and drug resistance among HIV-1 patients on antiretroviral treatment: a cross-sectional study in Soweto, South Africa. AIDS. 2010;24(11):1679-1687.
6. Hosseinipour MC, Kumwenda JJ, Weigel R, et al. Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline. HIV Med. 2010;11(8):510-518.
7. 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):1-5.
8. JTK 303 Public Chemical Database. PubChem Compound Summary (CID 5277135). Available from: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5277135. Accessed November 30, 2011.
9. Al-Mawsawi LQ, Al-Safi RI, Neamati N. Anti-infectives: clinical progress of HIV-1 integrase inhibitors. Expert Opin Emerg Drugs. 2008;13(2):213-225.
10. Kawaguchi I, Ishikawa T, Ishibashi M, Irie S, Kakee A. Gilead integrase inhibitor: safety and pharmacokinetics of single oral dose of JTK 303/GS-9137, a novel HIV integrase inhibitor, in healthy volunteers. 13th Conference on Retroviruses and Opportunistic Infections, Denver, USA, February 5-9, 2006. Available from: http://www.natap.org/2006/CROI/CROI_11.htm. Accessed November 30, 2011.
11. Ramanathan S, Wright M, West S, et al. Pharmacokinetics, metabolism, and excretion of ritonavir-boosted GS-9137 (Elvitegravir). Presented at: Eighth International Workshop on Clinical Pharmacology of HIV Therapy; April 16-18, 2007; Budapest, Hungary. Abstract 30.
12. 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(1):64-70.
13. 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 df in the initial treatment of HIV infection. AIDS. 2011;25(15):1881-1886.
14. German P, West S, Hui J, Kearney BP. Pharmacokinetic interaction between elvitegravir/ritonavir and dose-adjusted rifabutin. 9th International Workshop on Clinical Pharmacology of HIV Therapy, New Orleans, LA, April 7-9, 2008. Abstract P19. Available from: http://www.hiv-druginteractions.org/data/NewsItem/62_9PK_NewOrleans.pdf. Accessed November 30, 2011.
15. Mathias AA, Hinkle J, Shen G, et al. Effect of ritonavir-boosted tipranavir or darunavir on the steady-state pharmacokinetics of elvitegravir. J Acquir Immune Defic Syndr. 2008;49(2):156-162.
16. Ramanathan S, Mathias AA, Shen G, Holmes C, Kearney BP. Lack of clinically relevant drug-drug interaction between ritonavir-boosted GS-9137 (elvitegravir) and fosamprenavir/r. Poster exhibition: 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, Australia, July 22-25, 2007. Abstract WEPEB014.
17. Mathias A, West S, Enejosa J, Kearney B. A pharmacokinetic interaction between lopinavir/r and elvitegravir. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, USA, September 17-20, 2007. Abstract A-1418.
18. Ramanathan S, West S, Hui J, et al. Clinical pharmacokinetics of once-daily elvitegravir boosted by atazanavir versus ritonavir. 9th International Workshop on Clinical Pharmacology of HIV Therapy, New Orleans, USA, April 7-9, 2008. Abstract O18.
19. Mathias A, Ramanathan S, Hinkle J, West S, Enejosa J, Kearney B. Effect of atazanavir/r on the steady-state pharmacokinetics of elvitegravir. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, USA, September 17-20, 2007. Abstract A-1417.
20. Ramanathan S, Abel S, Tweedy S, West S, Hui J, Kearney BP. Pharmacokinetic interaction of ritonavir-boosted elvitegravir and maraviroc. J Acquir Immune Defic Syndr. 2010;53(2):209-214.
21. Ramanathan S, Kakuda TN, Mack R, West S, Kearney BP. Pharmacokinetics of elvitegravir and etravirine following coadministration of ritonavir-boosted elvitegravir and etravirine. Antivir Ther. 2008;13(8): 1011-1017.
22. Ramanathan S, Shen G, Cheng A, Kearney BP. Pharmacokinetics of emtricitabine, tenofovir, and GS-9137 following coadministration of emtricitabine/tenofovir disoproxil fumarate and ritonavir-boosted GS-9137. J Acquir Immune Defic Syndr. 2007;45(3): 274-279.
23. Ramanathan S, Shen G, Hinkle J, Enejosa J, Kearney BP. Pharmacokinetics of coadministered ritonavir-boosted elvitegravir and zidovudine, didanosine, stavudine or abacavir. J Acquir Immune Defic Syndr. 2007;46(2):160-166.
24. Ramanathan S, Shen G, Hinkle J, Enejosa J, Kearney BP. Pharmacokinetic evaluation of drug interaction with ritonavir-boosted HIV integrase inhibitor GS-9137 and acid reducing agents. 8th International Workshop on Clinical Pharmacology of HIV Therapy, Budapest, April 16-18, 2007. Abstract 69.
25. German P, Mathias A, West S, Chuck S, Kearney BP. Evaluation of ritonavir-boosted elvitegravir PK upon co-administration with a second potent CYP3A inhibitor, ketoconazole. 11th International Workshop on Clinical Pharmacology of HIV Therapy, Sorrento, Italy, April 5-7, 2010. Abstract 48.
26. German P, Wang M, Warren D, Kearney PB. Pharmacokinetic interaction between norgestimate/ethinyl estradiol and EVG/COB/FTC/TDF single tablet regimen. 12th International Workshop on Clinical Pharmacology of HIV Therapy, Miami, USA, April 13-15, 2011. Abstract 17.
27. Zolopa AR, Berger DS, Lampiris H, Zhong L, Chuck SL, Enejosa JV, et al. Activity of elvitegravir, a once-daily integrase inhibitor, against resistant HIV Type 1: results of a phase 2, randomized, controlled, dose-ranging clinical trial. J Infect Dis. 2010;201(6): 814-822.
28. Gilead Sciences. Safety and efficacy of GS-9350-boosted atazanavir compared to ritonavir-boosted atazanavir in combination with emtricitabine/tenofovir disoproxil fumarate in HIV-1 infected, antiretroviral treatment-naive adults. ClinicalTrials.gov identifier: NCT00892437. Ongoing study sponsored by Gilead Sciences. Trial began April 30, 2009, last updated October 12, 2011. Available from: http://clinicaltrials.gov/ct2/show/NCT00892437?term=GS-9350&rank=1. Accessed November 30, 2011.
29. 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(6):F7-F12.
30. Gilead Sciences. Gilead's Investigational Antiretroviral Quad Regimen Meets 48-Week Primary Objective in Pivotal Phase 3 Clinical Study 102. Press release. August 15, 2011. Available from: http://www.gilead.com/press_archive. Accessed November 30, 2011.
31. Molina J-M, LaMarca A, Andrade Villanueva J, et al; for the Study 145 Group. Elvitegravir once-daily is non inferior to raltegravir twicedaily in treatment experienced patients: 48 week results from a phase 3 multicenter, randomized, double blind study. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, July 17-20, 2011. Abstract WELBB05.
32. Ford N, Lee J, Andrieux-Meyer I, Calmy A. Safety, efficacy and pharmacokinetics of rilpivirine: a systematic review with an emphasis on resource-limited settings. HIV/AIDS (Auckl). 2011;3:35-44.
33. Blanco JL, Varghese V, Rhee SY, Gatell JM, Shafer RW. HIV-1 integrase inhibitor resistance and its clinical implications. J Infect Dis. 2011;203(9):1204-1214.
34. Shimura K, Kodama E, Sakagami Y, et al. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J Virol. 2008;82(2):764-774.
35. Goethals O, Clayton R, Van Ginderen M, et al. Resistance mutations in human immunodeficiency virus type 1 integrase selected with elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors. J Virol. 2008;82(21):10366-10374.
36. Garvey EP, Johns BA, Gartland MJ, et al. The naphthyridinone GSK364735 is a novel, potent human immunodeficiency virus type 1 integrase inhibitor and antiretroviral. Antimicrob Agents Chemother. 2008;52(3):901-908.
37. McColl DJ, Fransen S, Gupta S, et al. Resistance and cross-resistance to first generation integrase inhibitors: insights from a phase 2 study of elvitegravir (GS-9137). 16th International Drug Resistance Workshop; Barbados, Bridgetown, June 12-16, 2007. Abstract 9.
38. Métifiot M, Marchand C, Maddali K, Pommier Y. Resistance to integrase inhibitors. Viruses. 2010;2(7):1347-1366.
39. Goethals O, Clayton R, Van Ginderen M, et al. Resistance mutations in human immunodeficiency virus type 1 integrase selected with elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors. J Virol. 2008;82(21):10366-10374.
40. Métifiot M, Vandegraaff N, Maddali K, et al. Elvitegravir overcomes resistance to raltegravir induced by integrase mutation Y143. AIDS. 2011;25(9):1175-1178.
41. Davies MA, Moultrie H, Eley B, et al. Virologic failure and second-line antiretroviral therapy in children in South Africa - the leDEA Southern Africa collaboration. J Acquir Immune Defic Syndr. 2011;56(3): 270-278.
42. Médecins Sans Frontières. Untangling the web of antiretroviral price reductions. 14th ed. Geneva, 2011.
43. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Working Group of the Office of AIDS Research Advisory Council (OARAC): guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. October 14, 2011. Available at: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL. Accessed November 30, 2011.
44. Sato A, Kobayashi M, Yoshinaga T, et al. S/GSK1349572 is a potent next generation HIV integrase inhibitor. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Cape Town, South Africa, July 19-22, 2009. Abstract WEPEA097.
45. Underwood M, Johns B, Sato A, Fujiwara T, Spreen W. S/GSK1349572: a next generation integrase inhibitor with activity against integrase inhibitor resistant clinical isolates from patients experiencing virologic failure while on raltegravir therapy. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Cape Town, South Africa, July 19-22, 2009. Abstract WEPEA098.
46. Min S, Song I, Borland J, et al. Pharmacokinetics (PK) and safety in healthy subjects of S/GSK1349572, a next generation, once-daily HIV integrase inhibitor (INI). 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Cape Town, South Africa, July 19-22, 2009. Abstract WEPEA099.
47. Min S, Song I, Borland J, Chen S, Lou Y, Fujiwara T, et al. Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Antimicrob Agents Chemother. 2010;54(1):254-258.
48. Lalezari J, Sloan L, DeJesus E, et al. Potent antiviral activity of S/GSK1349572, a next generation integrase inhibitor (INI), in INI-Naive HIV-1-infected patients: ING111521 protocol. 5th IAS Conference on HIV Pathogenesis, treatment and prevention, Cape Town, South Africa, July 19-22, 2009. Abstract TUAB105.
49. Song I, Chen S, Lou Y, et al. Pharmacokinetic (PK) and pharmacodynamic (PD) relationship of S/GSK1349572, a next generation integrase inhibitor (INI), in HIV-1 infected patients. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Cape Town, South Africa, July 19-22, 2009. Abstract WePeB250.
50. Min S, DeJesus E, McCurdy L, et al. Pharmacokinetics (PK) and safety in healthy and HIV-infected subjects and short-term antiviral efficacy of S/GSK1265744, a next generation once daily HIV integrase inhibitor. The Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, September 12-15, 2009. Abstract H-1228.
51. GlaxoSmithKline. A single dose escalation study to investigate the safety, tolerability and pharmacokinetics of intramuscular and subcutaneous long acting GSK1265744 in healthy subjects. ClinicalTrials. gov identifier: NCT01215006. Sponsored by Gilead Sciences. 2010 [updated June 9, 2011]. Available from: http://clinicaltrials.gov/ct2/show/NCT01215006. Accessed November 30, 2011.