Short-term safety and antiretroviral activity of T-1249, a second-generation fusion inhibitor of HIV.
T-1249 is a 39-aa synthetic peptide that inhibits fusion of human immunodeficiency virus (HIV) to the host target cell. A 14-day open-label, phase 1/2 dose-escalation monotherapy study of the safety and antiretroviral activity of T-1249 was performed on 115 HIV-1-infected adults. At baseline, the majority of the patients had advanced HIV disease (baseline median CD4(+) cell count, 57 cells/microL) and had extensive pretreatment (i.e., pre-T-1249) experience with antiretroviral medications (median, 11 antiretroviral drugs). Patients received T-1249 monotherapy by subcutaneous injection, for 14 days, at doses ranging from 6.25 to 192 mg/day. T-1249 was generally well tolerated, and no dose-limiting toxicity was identified. Injection-site reactions were the most commonly reported adverse event (57%). Dose-dependent decreases in plasma HIV-1 RNA load were observed; the median maximum change from baseline across dose groups ranged from -0.29 log(10) copies/mL (95% confidence interval [CI], -0.43 to -0.05 log(10) copies/mL) for the lowest dose to -1.96 log(10) copies/mL (95% CI, -2.02 to -1.37 copies/mL) for the highest dose. These results indicate that T-1249 is a potent new therapeutic agent for HIV-1 infection.
Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Joseph J
JJ
Eron
Roy M
RM
Gulick
John A
JA
Bartlett
Thomas
T
Merigan
Roberto
R
Arduino
J Michael
JM
Kilby
Bienvenido
B
Yangco
Adriann
A
Diers
Claude
C
Drobnes
Ralph
R
DeMasi
Michael
M
Greenberg
Thomas
T
Melby
Claire
C
Raskino
Pam
P
Rusnak
Ying
Y
Zhang
Rebecca
R
Spence
G Diego
GD
Miralles
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008561:Membrane Fusion / Q000187:drug effects; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects* / Q000276:immunology; D012367:RNA, Viral / Q000097:blood
D019380:Anti-HIV Agents; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D010446:Peptide Fragments; D012367:RNA, Viral; C474741:peptide T1249