Enfuvirtide

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Enfuvirtide
Mass / length primary structure 36 amino acids, 4492  daltons
Identifier
External IDs
Drug information
ATC code J05 AX07
DrugBank DB00109
Drug class Fusion inhibitors

Enfuvirtide (ENF, trade name: Fuzeon , Hoffmann-La Roche ) is a drug used to treat HIV- infected patients. It belongs to the group of fusion inhibitors (entry inhibitors) .

structure

Acetyl- Y T S L I H SLI E ES Q N QQE K NEQELLEL D K W A SLWNW F -amid.

pharmacology

Enfuvirtide inhibits fusion of HIV-1 and the host cell and thus the infection of the cell . The first steps in this fusion consist in the attachment of the surface protein gp120 to the CD4 receptor and a co -receptor . This attachment causes conformational changes in the protein, thereby exposing gp41 and undergoing a conformational change. As a result, the membrane of the target cell and that of the virus come into contact and fuse together, allowing the virus to enter the cell. Enfuvirtide prevents the change in conformation by docking to gp41 and thus the infection.

Enfuvirtide is active against HIV-1; there is no activity against HIV-2. So far, no cross-resistance between the substance and other drugs has been found.

Pharmacokinetics

Enfuvirtide is rapidly broken down in the gastrointestinal tract and is therefore not orally bioavailable. After subcutaneous injection, the substance is well absorbed. After administration of 90 mg twice daily, the plasma concentrations fluctuated between about 3 and 5 µg / ml. The half-life is about 3.8 hours.

Side effects

Enfuvirtide is well tolerated. The most common side effects are mild local reactions at the injection site. The use of analgesics was required in 9.4% of patients . Treatment was discontinued in 3% of patients. Interactions are not yet known.

Web links

Individual evidence

  1. ^ AIDS Meds - American HIV Drugs Website .
  2. ↑ International Nonproprietary Names for Pharmaceutical Substances (INN) .
  3. ↑ Esté YES, Telenti A: HIV entry inhibitor . In: The Lancet . 370, No. 9581, July 2007, pp. 81-8. doi : 10.1016 / S0140-6736 (07) 61052-6 . PMID 17617275 .

literature

  • Greenberg ML, Melby T, Sista P, et al. Baseline and on-treatment susceptibility to enfuvirtide seen in TORO 1 and 2 to 24 weeks. Abstract 141, 10th CROI 2003, Boston.
  • Lalezari J, Cohen C, Eron J, and the T20-205 study group. Forty eight week analysis of patients receiving T-20 as a component of multidrug salvage therapy. Abstract LbPp116, XIII Int AIDS Conf 2000, Durban, South Africa.
  • Lalezari J, DeJesus E, Northfelt D, 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. Abstract 418, 9th CROI 2002, Seattle, USA.
  • Lazzarin A, Queiroz-Telles F, Frank I, et al. TMC114 provides durable viral load suppression in treatment-experienced patients: POWER 1 and 2 combined week 48 analysis. TUAB0104, XVI IAC 2006, Toronto.
  • Lu J, Sista P, Cammack N, Kuritzkes D, et al. Fitness of HIV-1 clinical isolates resistant to T-20 (enfuvirtide) . In: Antiviral Therapy , 2002, 7: S56
  • Walmsley S, Henry K, Katlama C, 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. Abstract 558, 10th CROI 2003, Boston.
  • Harris M, Joy R, Larsen G, et al. Enfuvirtide plasma levels and injection site reactions using a needle-free gas-powered injection system (Biojector) . In: AIDS , 2006, 20: 719-23. PMID 16514302
  • Hicks CB, Cahn P, Cooper DA, et al. Durable efficacy of tipranavir-ritonavir in combination with an optimized background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the RESIST studies: an analysis of combined data from two randomized open-label trials . In: The Lancet , 2006, 368: 466-475. PMID 16890833
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  • Kilby JM, Lalezari JP, Eron JJ, et al. The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus adults fusion, in HIV-infected. In: AIDS Res Hum Retroviruses , 2002, 18: 685-93. PMID 12167274
  • Lalezari JP, Henry K, O'Hearn M, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America . In: N Engl J Med . 2003, 348: 2175-85. PMID 12637625
  • Lalezari J, Godrich J, DeJesus E, et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5-tropic HIV-1: 24-week results of a phase 2b / 3 study in the US and Canada . Abstract 104LB, 14th CROI 2007, Los Angeles.
  • Lazzarin A, Clotet B, Cooper D, et al. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia . In: N Engl J Med . 2003, 348: 2186-95. PMID 12773645
  • Lehrman G, Hogue IB, Palmer S, et al. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study . In: Lancet 2005; 366: 549-55, PMID 16099290 .
  • Melby T, Sista P, DeMasi R, et al. Characterization of envelope glycoprotein gp41 genotype and phenotypic susceptibility to enfuvirtide at baseline and on treatment in the phase III clinical trials TORO-1 and TORO-2 . In: AIDS Res Hum Retroviruses , 2006; 22: 375-85. Abstract: PMID 16706613
  • Menzo S, Castagna A, Monachetti A, et al. Resistance and replicative capacity of HIV-1 strains selected in vivo by long-term enfuvirtide treatment . In: New Microbiol . 2004, 27: 51-61. PMID 15646065
  • Mink M, Mosier SM, Janumpalli S, et al. Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro . In: J Virol . 2005, 79: 12447-54. PMID 16160172
  • Molto J, Ruiz L, Valle M, et al. Increased antiretroviral potency by the addition of enfuvirtide to a four-drug regimen in antiretroviral-naive, HIV-infected patients . In: Antivir Ther . 2006; 11: 47-51. Abstract: PMID 16518959
  • Nelson M, Arasteh K, Clotet B, et al. Durable efficacy of enfuvirtide over 48 weeks in heavily treatment-experienced HIV-1-infected patients in the T-20 versus optimized background regimen only 1 and 2 clinical trials . In: J AIDS , 2005, 40: 404-12. PMID 16280694
  • Nelson M, Fätkenheuer G, Konourina I, et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5-tropic HIV-1 in Europe, Australia and North America: 24 week results. Abstract 104aLB, 14th CROI 2007, Los Angeles.
  • Oldfield V, Keating GM, Plosker G: Enfuvirtide: A Review of its Use in the Management of HIV Infection . In: Drugs , 2005, 65: 1139-60. PMID 15907147
  • Raffi F, Katlama C, Saag M, et al .: Week-12 response to therapy as a predictor of week 24, 48, and 96 outcome in patients receiving the HIV fusion inhibitor enfuvirtide in the T-20 versus Optimized Regimen Only (TORO ) trials . In: Clin Infect Dis . 2006; 42: 870-877, PMID 16477567 .
  • Stocker H, Kloft C, Plock N, et al. Pharmacokinetics of enfuvirtide in patients treated in typical routine clinical settings . In: Antimicrob Agents Chemother . 2006, 50: 667-73. PMID 16436725
  • Thompson M, DeJesus E, Richmond G, et al. Pharmacokinetics, pharmacodynamics and safety of once-daily versus twice-daily dosing with enfuvirtide in HIV-infected subjects . In: AIDS , 2006, 20: 397-404, PMID 16439873 .
  • Trottier B, Walmsley S, Reynes J, et al. Safety of enfuvirtide in combination with an optimized background of antiretrovirals in treatment-experienced HIV-1-infected adults over 48 weeks . In: JAIDS 2005, 40: 413-421, PMID 16280695 .
  • Youle M, Staszweski S, Clotet B, et al. Concomitant use of an active boosted protease inhibitor with enfuvirtide in treatment-experienced, HIV-infected individuals: recent data and consensus recommendations . In: HIV Clin Trials , 2006; 7: 86-96, PMID 16798623 .