Effects of a Novel Compound (AL 721) on HTLV-III Infectivity in Vitro

Abstract

This letter reports the results of a study indicating that AL 721 a lipid compound with a demonstrated ability to extract cholesterol from cellular membranes inhibits human T-lymphotropic virus type III (HTLV-III) infection of human peripheral-blood lymphocytes or an immortalized helper T-cell line (H9). When H9 cells were incubated with HTLV-III for 4 days reductions were detected in cell numbers and there were significant levels of reverse transciptase p15 and p24. After H9 cells were infected with HTLV-III in the presence of AL 721 there was a reduction in viral infectivity. The median dose for this effect was 100 mcg/ml of AL 721. It is not clear whether the virucidal effects of AL 721 are due to its actions on the retroviral envelope or on the host cell membrane. In preliminary clinical trials with elderly human subjects daily oral doses of AL 721 over a 6-week period restored diminished lymphocyte proliferative capacity and were well tolerated. AL 721 is considered a promising new candidate for investigation in the treatment of acquired immunodeficiency syndrome (AIDS) especially since it does not produce the side effects that are associated with reverse transcriptase inhibitors.