An open-label, dose-ranging trial of AL 721 in patients with persistent generalized lymphadenopathy and AIDS-related complex.
AL 721, a lipid mixture with reported in vitro activity against human immunodeficiency virus (HIV) via cell membrane or virion cholesterol depletion, was evaluated in a multicenter, open-label, dose-ranging trial. Forty men with persistent generalized lymphadenopathy or AIDS-related complex were treated with doses of 20, 30, 40, or 50 g orally twice daily for 8 weeks, and monitored for toxicity, disease progression, and with immunologic, virologic, and serum lipid profiles. The compound was found to be well tolerated over the broad range of doses examined; adverse reactions were confined to the gastrointestinal tract, of mild to moderate severity, and self-limited in duration. Modest weight gains observed on treatment were reversed within 4 weeks following cessation of therapy. While disease progression was not observed in this short-term study, we could find no indication of an immunorestorative or antiviral effect of AL 721, as determined by T-lymphocyte subset quantitation or HIV culture. All three patients who were HIV p24 antigenemic at entry retained positive antigen levels throughout treatment. As a consequence of therapy, however, significant increases in serum lipids were observed, including elevations in both triglyceride and total cholesterol levels. In conclusion, our experience on the largest group of HIV-infected patients treated with the highest doses of AL 721 provides no support for the use of this compound as an antiretroviral agent.
Mildvan
D
D
Beth Israel Medical Center, City University of New York 10003.
Buzas
J
J
Armstrong
D
D
Antoniskis
D
D
Sacks
H S
HS
Rhame
F S
FS
Mosbach
E W
EW
Pettinelli
C
C
D000386:AIDS-Related Complex / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005989:Glycerides / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D015337:Multicenter Studies as Topic; D010713:Phosphatidylcholines / Q000009:adverse effects / Q000627:therapeutic use*; D010714:Phosphatidylethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000187:drug effects
D000998:Antiviral Agents; D004338:Drug Combinations; D005989:Glycerides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C046637:neutral lipid, phosphatidylcholine, phosphatidylethanolamine drug combination