PMID- 15110129
OWN - NLM
STAT- MEDLINE
DCOM- 20040813
LR  - 20190922
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 26
IP  - 3
DP  - 2004 Mar
TI  - Enfuvirtide: a fusion inhibitor for the treatment of HIV infection.
PG  - 352-78
AB  - BACKGROUND: Drug resistance continues to be a major challenge in the treatment of 
      HIV-1 infection. Virtually all currently available antiretroviral medications 
      inhibit the viral reverse transcriptase or protease. Enfuvirtide is the first 
      fusion inhibitor approved by the US Food and Drug Administration for use in 
      combination with other antiretroviral agents for the treatment of HIV-1 infection 
      in treatment-experienced patients. OBJECTIVE: This paper describes the 
      pharmacologic properties and clinical usefulness of enfuvirtide. METHODS: 
      Relevant information was identified through searches of MEDLINE (1990 to October 
      2003), International Pharmaceutical Abstracts (1970 to October 2003), and meeting 
      abstracts of major HIV/AIDS conferences (1996-2003) using the search terms 
      enfuvirtide, pentafuside, T-20, DP-178, and fusion inhibitor. RESULTS: In vitro, 
      enfuvirtide exhibits activity against HIV-1 isolates that are resistant to all 
      other classes of anti-retroviral medications. Enfuvirtide blocks the entry of 
      HIV-1 into host cells by interfering with virus-cell fusion, making it unique 
      among licensed antiretroviral medications. In human adults, enfuvirtide has a 
      volume of distribution of 5.48 L, is highly bound to plasma protein (92%), has a 
      plasma elimination half-life of 3.8 hours, and is catabolized by peptidases and 
      proteinases in various tissues. Dose adjustment does not appear necessary on the 
      basis of age, race, or body weight, but may be warranted in women weighing <50 
      kg. A literature review did not identify any data on the disposition of 
      enfuvirtide in patients with hepatic or renal insufficiency. Clinical trials 
      suggest that enfuvirtide reduces plasma HIV-1 RNA levels in highly 
      treatment-experienced patients taking an optimized antiretroviral regimen. 
      Pivotal trials indicated a mean change in HIV-1 RNA of -1.48 log(10) copies/mL in 
      the enfuvirtide arm at week 48, compared with -0.63 log(10) copy/mL in the 
      control arm ( P<0.001 ). The mean absolute increase on CD4 cell count was 46 
      cells/mm(3) (91 cells/mm(3)) in the enfuvirtide arm vs 45 cells/mm(3) in the 
      control arm; P<0.001 ). The most commonly reported (>15 cases per 100 
      patient-years of exposure) adverse events (AEs) in clinical trials included 
      injection-site reactions, diarrhea, nausea, fatigue, insomnia, peripheral 
      neuropathy, headache, vomiting, and fever. The most commonly reported (> or =2%) 
      laboratory abnormalities (grade III or IV) were eosinophilia, anemia, and 
      increases in amylase, lipase, triglycerides, creatine phosphokinase, alanine 
      aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase. In 
      clinical trials, serious AEs leading to study discontinuation occurred in 12.9% ( 
      114/885 ) of patients in the enfuvirtide arm, compared with 10.7% ( 12/112 ) in 
      the control arm ( P = NS ). The recommended dosage of enfuvirtide is 90 mg SC BID 
      in adults and 2 mg/kg SC BID in children. Efficacy studies in children are 
      ongoing. CONCLUSION: Although additional studies are needed, enfuvirtide appears 
      to be a promising agent, in combination with other antiretroviral agents, for the 
      treatment of HIV infection in treatment-experienced patients.
FAU - Fung, Horatio B
AU  - Fung HB
AD  - Critical Care Center, Veterans Affairs Medical Center, Bronx, New York 10468, 
      USA. horatio.fung@med.va.gov
FAU - Guo, Yi
AU  - Guo Y
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (HIV Envelope Protein gp41)
RN  - 0 (HIV Fusion Inhibitors)
RN  - 0 (Peptide Fragments)
RN  - 19OWO1T3ZE (Enfuvirtide)
SB  - IM
MH  - Clinical Trials as Topic
MH  - Drug Interactions
MH  - Drug Resistance, Viral
MH  - Drug Therapy, Combination
MH  - Economics, Pharmaceutical
MH  - Enfuvirtide
MH  - HIV Envelope Protein gp41/*pharmacology/*therapeutic use
MH  - HIV Fusion Inhibitors/pharmacokinetics/*pharmacology/*therapeutic use
MH  - HIV Infections/*drug therapy
MH  - Humans
MH  - Peptide Fragments/pharmacokinetics/*pharmacology/*therapeutic use
RF  - 77
EDAT- 2004/04/28 05:00
MHDA- 2004/08/17 10:00
CRDT- 2004/04/28 05:00
PHST- 2004/01/13 00:00 [accepted]
PHST- 2004/04/28 05:00 [pubmed]
PHST- 2004/08/17 10:00 [medline]
PHST- 2004/04/28 05:00 [entrez]
AID - S014929180490032X [pii]
AID - 10.1016/s0149-2918(04)90032-x [doi]
PST - ppublish
SO  - Clin Ther. 2004 Mar;26(3):352-78. doi: 10.1016/s0149-2918(04)90032-x.