TY - JOUR
T1 - The safety and efficacy of combination yv-butyl-deoxynojirimycin (Sc-48334) and zidovudine in patients with hiv-1 infection and 200-500 cd4 cells/mm3
AU - Fischl, Margaret A.
AU - Resnick, Lionel
AU - Coombs, Robert
AU - Kremer, Alton B.
AU - Pottage, John C.
AU - Fass, Robert J.
AU - Fife, Kenneth H.
AU - Powderly, William G.
AU - Collier, Ann C.
AU - Aspinall, Richard L.
AU - Smith, Susan L.
AU - Kowalski, Kenneth G.
AU - Wallemark, Carl Bertil
N1 - Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 1994/2
Y1 - 1994/2
N2 - We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC- 48334) (an α-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated ≤ 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 ± 0.99 μg/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients. Although superiority of combination therapy was not seen, these data suggest that SC-48334 has anti-HIV activity and provide a rationale for the evaluation of better tolerated compounds of this class.
AB - We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC- 48334) (an α-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated ≤ 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 ± 0.99 μg/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients. Although superiority of combination therapy was not seen, these data suggest that SC-48334 has anti-HIV activity and provide a rationale for the evaluation of better tolerated compounds of this class.
KW - Combination therapy
KW - Glucosidase inhibitor
KW - HIV
KW - N-Butyl-deoxynojirimycin (SC-48334)
UR - http://www.scopus.com/inward/record.url?scp=0028088988&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028088988&partnerID=8YFLogxK
M3 - Article
C2 - 7905523
AN - SCOPUS:0028088988
VL - 7
SP - 139
EP - 147
JO - Journal of acquired immune deficiency syndromes (1999)
JF - Journal of acquired immune deficiency syndromes (1999)
SN - 1525-4135
IS - 2
ER -