Enfuvirtide: A novel agent for the treatment of HIV-1 infection

Annals of Pharmacotherapy

Volumn 37, Issue 10, 2003, Pages 1448-1456

  Duffalo, Melody L ^a   James, Christopher W ^b  

^a PENN PRESBYTERIAN MEDICAL CENTER   (United States)

^b CHRISTIANA CARE HEALTH SYSTEM   (United States)

Author keywords

Enfuvirtide; Fusion inhibitor; Fuzeon; HIV

Indexed keywords

ABACAVIR; AMPRENAVIR; CD4 ANTIGEN; DELAVIRDINE; DIDANOSINE; EFAVIRENZ; ENFUVIRTIDE; GLYCOPROTEIN GP 41; INDINAVIR; LAMIVUDINE; LOPINAVIR; NELFINAVIR; NEVIRAPINE; PROTEINASE INHIBITOR; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; VIRUS RNA; ZIDOVUDINE;

ASPERGILLOSIS; CHILL; CLINICAL TRIAL; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG RESISTANCE; DRUG SAFETY; EOSINOPHILIA; ERYTHEMA; FEVER; GLOMERULONEPHRITIS; GUILLAIN BARRE SYNDROME; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPOTENSION; INHIBITION KINETICS; INJECTION PAIN; INJECTION SITE; LEUKOENCEPHALOPATHY; LYMPHOCYTE COUNT; META ANALYSIS; NAUSEA; PNEUMONIA; PRIORITY JOURNAL; RASH; REVIEW; RIGOR; RNA ANALYSIS; SIDE EFFECT; SKIN INDURATION; SKIN NODULE; VIROLOGY; VIRUS ISOLATION; VOMITING;

HIV ENVELOPE PROTEIN GP41; HIV INFECTIONS; HIV-1; HUMANS; INJECTIONS, SUBCUTANEOUS; META-ANALYSIS; PEPTIDE FRAGMENTS;

EID: 0141557901     PISSN: 10600280     EISSN: None     Source Type: Journal    
DOI: 10.1345/aph.1D143     Document Type: Review

References (40)

1. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents, July 14, 2003. Panel on Clinical Practices for Treatment of HIV Infection. www.aidsinfo.nih.gov/guidelines/adult/AA_071403.pdf (accessed 2003 Jul 14).
2. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998; 338:853-60.
3. Deeks SG, Smith M, Holodniy M, Kahn JO. HIV-1 protease inhibitors. A review for clinicians. JAMA 1997;277:145-53.
4. Kakuda TN, Struble KA, Piscitelli SC. Protease inhibitors for the treatment of human immunodeficiency virus infection. Am J Health Syst Pharm 1998;55:233-54.
5. D'Souza MP, Cairns JS, Plaeger SF. Current evidence and future direction for targeting HIV entry - therapeutic and prophylactic strategies. JAMA 2000;84:215-22.
6. Roche and Trimeris Pharmaceuticals. Preliminary 48-week results show longer term response in HIV patients treated with Fuzeon™ (enfuvirtide), first fusion inhibitor. Press release, March 20, 2003. www.trimeris. com/news/pr/2003/0303203.html (accessed 2003 Mar 24).
7. Package insert. Fuzeon (enfuvirtide). Nutley, NJ and Durham, NC: Hoffman-La Roche and Trimeris, March 2003.
8. Chan DC, Chutkowski CT, Kim PS. Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target. Proc Natl Acad Sci U S A 1998;95:15613-7.
9. Follis KE, Larson SJ, Lu M, Nunberg JH. Genetic evidence that interhelical packing interactions in the gp41 core are critical for transition of the human immunodeficiency virus type 1 envelope glycoprotein to the fusion-active state. J Virol 2002;76:7356-62.
10. Wild C, Greenwell T, Matthews T. A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell-cell fusion. AIDS Res Human Retroviruses 1993;9:1051-3.
11. Greenberg ML, Sista P, Miralles GD. Enfuvirtide (T-20) and T-1249 resistance: observations from Phase II clinical trials of enfuvirtide in combination with oral antiretrovirals and a Phase I/II dose-ranging monotherapy trial of T-1249 (abstract 128). Antiviral Ther 2002;7(suppl 1):S106.
12. Sista P, Melby T, Greenberg ML, Davison D, Jin L, Mosier S, et al. Characterization of baseline and treatment-emergent resistance to T-20 (enfuvirtide) observed in Phase II clinical trials: substitutions in gp41 amino acids 36-45 and enfuvirtide susceptibility of virus isolates (abstract 21). Antiviral Ther 2002;7(suppl 1):S16.
13. Rimsky LT, Shugars DC, Matthews TJ. Determinants of human immunodeficiency virus type 1 resistance to gp41-derived inhibitory peptides. J Virol 1998;72:986-93.
14. Wei X, Decker JM, Liu H, Zhang Z, Arani RB, Kilby JM, et al. Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 2002;46:1896-905.
15. Mink M, Greenberg M, Mosier S, Janumpalli S, Davison D, Jin L, et al. Impact of HIV-1 gp41 amino acid substitutions (positions 36-45) on susceptibility to T-20 (enfuvirtide) in vitro: analysis of primary virus isolates recovered from patients during chronic enfuvirtide treatment and site-directed mutants in NL4-3. Antivir Ther 2002;7(suppl 1):S17-8.
16. Greenberg ML, Melby T, Sista P, DeMasi R, Cammack N, Salgo M, et al. Baseline and on-treatment susceptibility to enfuvirtide seen in TORO 1 and TORO 2 to 24 weeks (abstract 141). Presented at: 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 10-14, 2003.
17. PRNewswire. Virologic announces broadened agreement with Roche and Trimeris for use of its HIV drug resistance testing technology. Press Release, October 16, 2001. www.aegis.com/news/pr/2001/PR011032. html (accessed 2003 Feb 12).
18. Lalezari JP, Henry K, O'Hearn M, Montaner JSG, Piliero PJ, Trottier B, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med 2003;348:2175-85.
19. Virologic pipeline. www.virologicpipeline.com/410.asp?show=410 (accessed 2003 Mar 27).
20. Miralles GD, Lalezari JP, Bellos N, Richmond G, Zhang Y, Murchison H, et al. T-1249 demonstrates potent antiviral activity over 10-day dosing in most patients who have failed a regimen containing enfuvirtide: planned interim analysis of T1249-102. A Phase I/II study (abstract 597). Presented at: 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 10-14, 2003.
21. Kilby JM, Hopkins S, Venetta TN, DiMassimo B, Cloud GA, Lee JY, et al. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nature Med 1998;4:302-7.
22. Kilby JM, Lalezari JP, Eron JJ, Carlson M, Cohen C, Arduino RC, et al. The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults. AIDS Res 2002;18:685-93.
23. Lalezari J, Cohen C, Eron J, Kilby M, Nelson E, Sista P, and the T20-205 study group. Forty-eight week analysis of patients receiving T-20 as a component of multidrug salvage therapy (abstract LbPp116). Presented at: XIII International AIDS Conference, Durban, South Africa, July 9-14, 2000.
24. Wheat LJ, Lalezari J, Kilby M, Wheeler D, Salgo M, DeMasi R, et al. A week-48 assessment of high strength T-20 formulations in multi-class experienced patients (abstract 417-W). Presented at: 9th Conference on Retroviruses and Opportunistic Infections, Seattle, February 24-28, 2002.
25. Patel IH, Lalezari J, Dorr A, Hawker N, Siddique Z, Kolis S, et al. T-20 is optimally absorbed from 3 different subcutaneous injection sites (abstract TuPeB4542). Presented at: XIV International AIDS Conference, Barcelona, July 7-12, 2002.
26. Lalezari JP, Eron JJ, Carlson M, Cohen C, DeJesus E, Arduino RC, et al. A Phase II clinical study of the long-term safety and antiviral activity of enfuvirtide-based antiretroviral therapy. AIDS 2003;17:691-8.
27. Lalezari J, Drucker J, DeMasi R, Hopkins S, Salgo M. A controlled Phase II trial assessing three doses of T-20 in combination with abacavir, amprenavir, low dose ritonavir and efavirenz in non-nucleoside naïve protease inhibitor experienced HIV-1 infected adults (abstract LB5). Presented at: 8th Conference of Retroviruses and Opportunistic Infections, Chicago, February 4-8, 2001.
28. Lalezari J, DeJesus E, Northfelt D, Richmond G, Delehanty J, DeMasi R, et al. A week 48 assessment of a randomized, controlled, open-label Phase II trial (T20-206) evaluating 3 doses of T-20 in PI-experienced, NNRTI-naïve patients infected with HIV-1 (poster 418-W). Presented at: 9th Conference on Retroviruses and Opportunistic Infections, Seattle, February 24-28, 2002.
29. Lazzarin A, Clotet B, Cooper D, Reynes J, Arasteh K, Nelson M, et al. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med 2003;348:2186-95.
30. Lange J, Lazzarin A, Clotet B, Cooper D, Reynes J, Arasteh K, et al. Enfuvirtide (T-20) in combination with an optimized background (OB) regimen vs. OB alone: week 24 response among categories of baseline demographics, treatment experience and HIV antiretroviral resistance (abstract PL 14.3). Presented at: Sixth International Congress on Drug Therapy in HIV infection, Glasgow, November 17-21, 2002.
31. Delfraissy J-F, Montaner J, Eron J, DeMasi R, Chung J, Drobnes C, et al. Summary of pooled efficacy and safety analyses of enfuvirtide treatment for 24 weeks in TORO 1 and TORO 2 Phase III trials in highly antiretroviral therapy experienced patients (abstract 568). Presented at: 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 10-14, 2003.
32. Boyd M, Ruxrungtham K, Zhang X, Bellibas E, Buss NE, Patel IH. Enfuvirtide: investigations on the drug interaction potential in HIV-infected patients (abstract 541). Presented at: 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 10-14, 2003.
33. Walmsley S, Henry K, Katlama C, Nelson M, Lazzarin A, Reynes J, et al. Lack of influence of gp41 antibodies that cross-react with enfuvirtide on the efficacy and safety of enfuvirtide in TORO 1 and TORO 2 Phase III trials. Presented at: 10th Conference on Retroviruses and Opportunistic Infections (abstract 558). Boston, February 10-14, 2003.
34. Ball RA, Kinchelow T. Pathology of injection site reactions with enfuvirtide (abstract 714). Presented at: 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 10-14, 2003.
35. Kosel B, Church J, Cunningham C, Sista P, Aweeka F, and the PACTG P1005 StudyTeam. Pharmacokinetics (PK) of selected doses of T-20, a fusion inhibitor, in HIV-1-infected children (abstract 726). Presented at: 8th Conference on Retroviruses and Opportunistic Infections, Chicago, February 4-8, 2001.
36. Church JA, Cunningham C, Hughes M, Palumbo P, Mofenson LM, Delora P, et al. Safety and antiretroviral activity of chronic subcutaneous administration of T-20 in human immunodeficiency virus 1-infected children. Pediatr Infect Dis J 2000;21:653-9.
37. Drug topics redbook, 2002. Montvale, NJ: Thomson Medical Economics, 2002.
38. Reuters Health Information. Roche, Trimeris set record US price for AIDS drug. March 20, 2003. www.aegis.com/news/re/2003/RE030319. html (accessed 2003 Mar 24).
39. AIDS reference guide, monthly update #176, January, 2003:1.
40. Roche and Trimeris Pharmaceuticals. Roche and Trimeris Announce U.S. FUZEON™ (enfuvirtide) progressive distribution and support programs. Press release, March 20, 2003. www.trimeris.com/news/pr/2003/0303201. html (accessed 2003 Mar 24).