Raltegravir: The first in a new class of integrase inhibitors for the treatment of HIV

Expert Review of Anti-Infective Therapy

Volumn 6, Issue 4, 2008, Pages 419-426

  Sayana, Shilpa ^a   Khanlou, Homayoon ^a  

^a AIDS HEALTHCARE FOUNDATION   (United States)

Author keywords

AIDS; Antiretrovial therapy; HIV; Integrase inhibitor; Raltegravir

Indexed keywords

ANTIRETROVIRUS AGENT; ATAZANAVIR; EFAVIRENZ; ELVITEGRAVIR; LAMIVUDINE; PLACEBO; RALTEGRAVIR; RIFAMPICIN; RITONAVIR; TENOFOVIR; TIPRANAVIR; VIRUS RNA; 2 PYRROLIDONE DERIVATIVE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; CROSS RESISTANCE; DIARRHEA; DNA INTEGRATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EXCRETION; DRUG FATALITY; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG STRUCTURE; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; GENE MUTATION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; KIDNEY FUNCTION; LIVER FUNCTION; MAXIMUM PLASMA CONCENTRATION; MONOTHERAPY; NAUSEA; REBOUND; SIDE EFFECT; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; VIRUS LOAD; VIRUS REPLICATION; VIRUS STRAIN; CHEMISTRY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; REVIEW;

ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; HIV INFECTIONS; HUMANS; PYRROLIDINONES;

EID: 54449088130     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/14787210.6.4.419     Document Type: Article

References (22)

1. Hammer S, Saag M, Schechter M et al. Treatment for adult HIV infection: 2006 recommendations of the international AIDS Society - USA Panel. JAMA 296, 827-843 (2006).
2. Formulary Submission Dossier of ISENTRESS™ (Raltegravir), received October 24, 2007.
3. Teppler H, Azrolan N, Chen J. Differential effect of MK-0518 and efavirenz on serum lipids and lipoproteins in antiretroviral therapy (ART)-naive patients. Presented at: 46th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, CA, USA, 27-30 September 2006 (Abstract H-256a).
4. 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. 35(9), 1657-1663 (2007).
5. Grinsztejn B, Nguyen B-Y, 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 randomized controlled trial. Lancet 369, 1261-1269 (2007).
6. Markowitz M, Nguyen B-Y, Gotuzzo F et al. Potent antiretroviral effect of MK-0518, a novel HIV-1 integrase inhibitor, as part of combination ART in treatment-naive HIV-1 infected patients. Presented at: 16th International AIDS Conference. Toronto, Canada, 13-18 August 2006 (Abstract THLB0214).
7. Butler SL, Hansen MST, Bushman FD. A quantitative assay for HIV DNA integration in vivo. Nat. Med. 7(5), 631-634 (2001).
8. Hazuda DJ, Felock P, Witmer M et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 287, 646-650 (2000).
9. Wiskerchen M, Muesing MA. Human immunodeficiency virus type 1 integrase: effects of mutations on viral ability to integrate, direct viral gene expression from unintegrated viral DNA templates, and sustainviral propagation in primary cells. J. Virol. 69(1), 376-386 (1995).
10. Package insert, ISENTRESS™ (raftegravir), Merk & Co., Inc. October 2007.
11. Petry AS, Hanley WD, Silk G et al. Effect of Severe renal insufficiency on raltegravir (RAL) pharmacokinetics. Presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Chicago, IL, USA, 17-20 September 2007 (Abstract A-1424).
12. Markowitz M, Morales-Ramirez JO, Nguyen B-Y et al. Antireroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integarse, dosed as monotherapy for 10 days in treatment-naive HIV-1 infected individuals. J. Acquir. Immune Defic. Syndr. 43, 509-515 (2006).
13. Markowitz M, Nguyen BY, Gotuzzo E, et al.; Protocol 004 Part II Study Team. 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. 46(2), 125-133 (2007).
14. Cooper D, Gatell JM, Rockstroh J et al. Results of BENCHMRK-1, a Phase III study evaluating the efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus. Presented at: 14th Conference on Retroviruses and Opportunistic Infections (CROI). Los Angeles, CA, USA, 25-28 Febuary 2007 (Abstract 105a LB).
15. Steigbigel R, Kumar P, Eton J et al. Results of BENCHMRK-2, a Phase III study evaluating the efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus. Presented at: 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles, CA, USA, 25-28 Febuary 2007 (Abstract 105b LB).
16. Cooper D, Gatell J, Rockstroh J et al. 48-week results from BENCHMRK-1, a Phase III study of raltegravir in patients failing ART with triple-class resistant HIV-1. Presented at: 15th Conference on Retroviruses and Opportunistic Infections, Boston, MA. USA 3-6 February 2008 (Abstract 788).
17. Steigbigel R, Kumar P, Eron J et al. 48-week results from BENCHMRK-2, a Phase III study of raltegravir in patients failing ART with triple-class resistant HIV. Presented at: 15th Conference on Retroviruses and Opportunistic Infections, Boston, MA, 3-6 February 2008 (Abstract 789).
18. DeJesus E, Cohen C, Elion R et al. First report of raltegravir (RAL, MK-0518) use after virologic rebound on elvitegravir (EVT, GS 9137). Presented at: 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Sydney, Australia, 22-25 July 2007 (Abstract TUPEB032).
19. McColl DJ, Fransen S, Gupta S et al. Resistance and cross-resistance to first generation integrase inhibitors: insights from a Phase II study of elvitegravir (GS-9137). Presented at: XVI International HIV Drug Resistance Workshop. Barbados, June 12-16 2007 (Abstract 9).
20. Ceccherini-Silberstein F, Van Baelen K, Armenia D et al. Novel HIV-1 integrase mutations, found as minority quasispecies in patients naïve to integrase inhibitors, are associated with decreased susceptibility to integrase inhibitors in vitro. Presented at: 15th Conference on Retroviruses and Opportunistic Infections. Boston, MA, USA, 3-6 February 2008 (Abstract 876).
21. Roquebert B, Damond F, Collin G et al. Phenotypic susceptibility in vitro to raltegravir and elvitegravir and polymorphism of the integrase gene of HIV-2 clinical isolates. Presented at: 15th Conference on Retroviruses and Opportunistic Infections (CROI), Boston, MA, USA 3-6 February 2008 (Abstract 886).
22. Murray JM, Emery S, Kelleher AD et al. Antiretroviral therapy with the integrase inhibitor raltegravir alters decay kinetics of HIV, significantly reducing the second phase. AIDS. 21(17), 2315-2321 (2007).