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: M A Fischl, L Resnick, R Coombs, A B Kremer, J C Pottage Jr, R J Fass, K H Fife, W G Powderly, A C Collier, R L Aspinall
• Journal: Journal of acquired immune deficiency syndromes (J Acquir Immune Defic Syndr (1988)) Vol. 7 Issue 2 Pg. 139-47 (Feb 1994) ISSN: 0894-9255 [Print] United States
• PMID: 7905523 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• HIV Core Protein p24
• Hemoglobins
• RNA, Viral
• beta 2-Microglobulin
• 1-Deoxynojirimycin
• Zidovudine
• miglustat

Topics

• 1-Deoxynojirimycin (adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
• Adult
• Antiviral Agents (adverse effects, pharmacokinetics, therapeutic use)
• CD4-Positive T-Lymphocytes (cytology)
• Diarrhea (chemically induced)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• HIV Core Protein p24 (blood)
• HIV Infections (drug therapy, immunology)
• HIV-1 (drug effects, genetics)
• Hemoglobins (analysis)
• Humans
• Leukocyte Count
• Male
• Neutrophils (drug effects)
• Paresthesia (chemically induced)
• RNA, Viral (blood)
• Zidovudine (adverse effects, pharmacokinetics, therapeutic use)
• beta 2-Microglobulin (analysis)