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An open-label, dose-ranging trial of AL 721 in patients with persistent generalized lymphadenopathy and AIDS-related
D Mildvan1, J Buzas, D Armstrong
1Beth Israel Medical Center, City University of New York 10003.
Insights
AL 721, a lipid mixture, showed no antiviral or immunorestorative effects in human immunodeficiency virus (HIV) patients. The compound was well-tolerated but increased serum lipids, offering no support for its use as an antiretroviral agent.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- AL 721 is a lipid mixture with demonstrated in vitro activity against human immunodeficiency virus (HIV).
- Its proposed mechanism involves depleting cholesterol from cell membranes or virions.
Purpose of the Study:
- To evaluate the safety and efficacy of AL 721 in patients with HIV.
- To assess AL 721's impact on immunologic, virologic, and lipid profiles.
Main Methods:
- A multicenter, open-label, dose-ranging trial involving 40 men with persistent generalized lymphadenopathy or AIDS-related complex.
- Treatment with AL 721 at doses of 20, 30, 40, or 50 g orally twice daily for 8 weeks.
- Monitoring for toxicity, disease progression, and changes in immunologic, virologic, and serum lipid profiles.
Main Results:
- AL 721 was well-tolerated, with mild to moderate, self-limiting gastrointestinal adverse reactions.
- No disease progression was observed during the short-term study.
- No evidence of immunorestorative or antiviral effects was found, with HIV p24 antigen levels remaining positive in all treated patients.
- Significant increases in serum triglyceride and total cholesterol levels were observed.
Conclusions:
- AL 721 did not demonstrate immunorestorative or antiviral effects in HIV-infected patients.
- The observed increases in serum lipids suggest potential adverse cardiovascular implications.
- The study does not support the use of AL 721 as an antiretroviral agent.
Abstract:
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.