The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults.
Enfuvirtide (T-20) is a novel antiretroviral agent that blocks HIV-1 cell fusion. A 28-day randomized dose-comparison study was conducted to determine the safety, pharmacokinetics, and antiviral activity of enfuvirtide in 78 HIV-infected adults, most with extensive treatment experience. Patients received enfuvirtide, added to a failing regimen, either by continuous subcutaneous infusion (CSI: 12.5, 25, 50 or 100 mg/day) or by subcutaneous (SC) injection (50 or 100 mg twice daily). Dose-related decreases in viral load were observed, with a maximum mean reduction from baseline of 1.6 log(10) copies/ml (p< 0.001) seen in the 100 mg bid SC group. Most responses diminished by 28 days. Plasma pharmacokinetics and antiviral responses were more consistent for SC injection than for CSI because of technical difficulties experienced with CSI. Injection site reactions were common but generally mild. These results indicate that enfuvirtide is a promising new therapeutic agent for HIV-infected patients, including those with prior antiretroviral treatment.
Kilby
J Michael
JM
UAB HIV Outpatient Clinic, University of Alabama at Birmingham, CCB 245A, 908 20th Street South, Birmingham, AL 35294-2050, USA. mkilby@uab.edu
Lalezari
Jacob P
JP
Eron
Joseph J
JJ
Carlson
Margrit
M
Cohen
Calvin
C
Arduino
Roberto C
RC
Goodgame
Jeffrey C
JC
Gallant
Joel E
JE
Volberding
Paul
P
Murphy
Robert L
RL
Valentine
Fred
F
Saag
Michael S
MS
Nelson
Emily L
EL
Sista
Prakash R
PR
Dusek
Alex
A
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D004305:Dose-Response Relationship, Drug; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects* / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007279:Injections, Subcutaneous; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D012367:RNA, Viral; D000077560:Enfuvirtide