title: The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3.
abstract: 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 alpha-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated < or = 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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: University of Miami School of Medicine, Florida.
authors.forename: M A
authors.initials: MA
authors.lastname: Fischl
authors.forename: L
authors.initials: L
authors.lastname: Resnick
authors.forename: R
authors.initials: R
authors.lastname: Coombs
authors.forename: A B
authors.initials: AB
authors.lastname: Kremer
authors.forename: J C
authors.initials: JC
authors.lastname: Pottage
authors.forename: R J
authors.initials: RJ
authors.lastname: Fass
authors.forename: K H
authors.initials: KH
authors.lastname: Fife
authors.forename: W G
authors.initials: WG
authors.lastname: Powderly
authors.forename: A C
authors.initials: AC
authors.lastname: Collier
authors.forename: R L
authors.initials: RL
authors.lastname: Aspinall
mesh_terms: D017485:1-Deoxynojirimycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010292:Paresthesia / Q000139:chemically induced; D012367:RNA, Viral / Q000097:blood; D015215:Zidovudine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001613:beta 2-Microglobulin / Q000032:analysis
chemical_list: D000998:Antiviral Agents; D016655:HIV Core Protein p24; D006454:Hemoglobins; D012367:RNA, Viral; D001613:beta 2-Microglobulin; D017485:1-Deoxynojirimycin; D015215:Zidovudine; C059896:miglustat