PMID- 14518696
OWN - NLM
STAT- MEDLINE
DCOM- 20040122
LR  - 20201208
IS  - 1359-6535 (Print)
IS  - 1359-6535 (Linking)
VI  - 8
IP  - 4
DP  - 2003 Aug
TI  - A controlled Phase II trial assessing three doses of enfuvirtide (T-20) in 
      combination with abacavir, amprenavir, ritonavir and efavirenz in non-nucleoside 
      reverse transcriptase inhibitor-naive HIV-infected adults.
PG  - 279-87
AB  - Enfuvirtide is a novel antiretroviral that blocks HIV-1 cell fusion and viral 
      entry. This Phase II, controlled, open-label, randomized, multicentre 
      dose-ranging trial explored the safety, antiviral activity and pharmacokinetics 
      of enfuvirtide, administered by subcutaneous (s.c.) injection, in 71 
      HIV-1-infected, protease inhibitor-experienced, non-nucleoside reverse 
      transcriptase inhibitor (NNRTI)-naive adults for 48 weeks. Study participants 
      were randomized to receive enfuvirtide at a deliverable dose of 45, 67.5 or 90 mg 
      twice daily; the 45 mg twice daily dose required 2 injections/day, while the 
      higher doses required 4 injections/day. A background oral antiretroviral (ARV) 
      regimen of abacavir (300 mg twice daily), amprenavir (1200 mg twice daily), 
      ritonavir (200 mg twice daily) and efavirenz (600 mg once daily) was provided 
      with enfuvirtide. A control group received the background ARV regimen alone. All 
      potential participants underwent an HIV genotype at screen to ensure a homogenous 
      population and to exclude patients with evidence of genotypic resistance to 
      NNRTIs. Overall, the tolerability of the combination of abacavir, amprenavir, 
      ritonavir, efavirenz and enfuvirtide was generally comparable to control through 
      48 weeks. No enfuvirtide dose-dependent adverse events (AEs) were observed across 
      treatment groups. Injection site reactions (ISRs) occurred at least once in 68.5% 
      of the enfuvirtide-treated population, and most ISRs were mild to moderate in 
      severity, with no apparent dose relationship. Excluding ISRs, the most common 
      treatment-emergent AEs were nausea, diarrhoea, dizziness and fatigue; with no 
      clinically significant differences in the incidence of AEs observed between the 
      control and enfuvirtide groups. Each treatment group benefited from ARV therapy, 
      with a trend of increasing antiviral and immunological activity associated with 
      increasing enfuvirtide dose. At 48 weeks, the median HIV-1 RNA change from 
      baseline for the ITT population was -2.24 log10 copies/ml for the combined 
      enfuvirtide groups compared with -1.87 log10 copies/ml for the control group. In 
      addition, 54.9% of patients in the enfuvirtide group achieved HIV-1 RNA < or = 
      400 copies/ml versus 36.8% of patients in the control group. These results 
      indicate that enfuvirtide has a favourable safety profile and is a promising new 
      antiviral agent for HIV-infected patients who have been on previously failing ARV 
      regimens.
FAU - Lalezari, Jacob P
AU  - Lalezari JP
AD  - Quest Clinical Research and Mount Zion Hospital/UCSF, San Francisco, Calif., USA. 
      drjay@questclinical.com
FAU - DeJesus, Edwin
AU  - DeJesus E
FAU - Northfelt, Donald W
AU  - Northfelt DW
FAU - Richmond, Gary
AU  - Richmond G
FAU - Wolfe, Peter
AU  - Wolfe P
FAU - Haubrich, Richard
AU  - Haubrich R
FAU - Henry, David
AU  - Henry D
FAU - Powderly, William
AU  - Powderly W
FAU - Becker, Stephen
AU  - Becker S
FAU - Thompson, Melanie
AU  - Thompson M
FAU - Valentine, Fred
AU  - Valentine F
FAU - Wright, David
AU  - Wright D
FAU - Carlson, Margrit
AU  - Carlson M
FAU - Riddler, Sharon
AU  - Riddler S
FAU - Haas, Frances F
AU  - Haas FF
FAU - DeMasi, Ralph
AU  - DeMasi R
FAU - Sista, Prokash R
AU  - Sista PR
FAU - Salgo, Miklos
AU  - Salgo M
FAU - Delehanty, John
AU  - Delehanty J
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Alkynes)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Benzoxazines)
RN  - 0 (Carbamates)
RN  - 0 (Cyclopropanes)
RN  - 0 (Dideoxynucleosides)
RN  - 0 (Furans)
RN  - 0 (HIV Envelope Protein gp41)
RN  - 0 (HIV Fusion Inhibitors)
RN  - 0 (Oxazines)
RN  - 0 (Peptide Fragments)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 0 (Sulfonamides)
RN  - 19OWO1T3ZE (Enfuvirtide)
RN  - 5S0W860XNR (amprenavir)
RN  - JE6H2O27P8 (efavirenz)
RN  - O3J8G9O825 (Ritonavir)
RN  - WR2TIP26VS (abacavir)
SB  - IM
MH  - Adult
MH  - Alkynes
MH  - Anti-HIV Agents/*administration & dosage/therapeutic use
MH  - Benzoxazines
MH  - Carbamates
MH  - Cyclopropanes
MH  - Dideoxynucleosides/administration & dosage/therapeutic use
MH  - Drug Therapy, Combination
MH  - Enfuvirtide
MH  - Female
MH  - Furans
MH  - HIV Envelope Protein gp41/*administration & dosage/adverse effects/therapeutic 
      use
MH  - HIV Fusion Inhibitors/*administration & dosage/adverse 
      effects/pharmacokinetics/therapeutic use
MH  - HIV Infections/*drug therapy/immunology/virology
MH  - HIV-1/drug effects/physiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Oxazines/administration & dosage/therapeutic use
MH  - Peptide Fragments/*administration & dosage/adverse 
      effects/pharmacokinetics/therapeutic use
MH  - Reverse Transcriptase Inhibitors/administration & dosage/therapeutic use
MH  - Ritonavir/administration & dosage/therapeutic use
MH  - Sulfonamides/administration & dosage/therapeutic use
MH  - Treatment Outcome
MH  - Viral Load
EDAT- 2003/10/02 05:00
MHDA- 2004/01/24 05:00
CRDT- 2003/10/02 05:00
PHST- 2003/10/02 05:00 [pubmed]
PHST- 2004/01/24 05:00 [medline]
PHST- 2003/10/02 05:00 [entrez]
PST - ppublish
SO  - Antivir Ther. 2003 Aug;8(4):279-87.