APPRAISAL OF POTENTIAL THERAPEUTIC INDEX OF ANTIOXIDANTS ON THE BASISOF THEIR IN-VITRO EFFECTS ON HIV REPLICATION IN MONOCYTES AND INTERLEUKIN 2-INDUCED LYMPHOCYTE-PROLIFERATION

Antioxidant molecules have been suggested to be of therapeutic value i n the treatment of HIV-infected patients. To evaluate this possibility , we examined in vitro the effects of two types of antioxidant molecul es in terms of inhibition of HIV replication in monocytes, one of the main reservoirs of HIV,(1,2) and also in terms of modulation of the im mune competence as measured by PBMC proliferation. We tested the effec ts of BHA, a phenolic, lipid-soluble, chain-breaking antioxidant, and NAC, a known glutathione precursor with some direct free-radical scave nging properties as well, on the regulation of HIV-1 expression in lat ently infected U1 cells and in productively and chronically infected U 937 cells. Both antioxidants inhibited TNF- or PMA-induced NF-kappa B activity in U1 cells, as well as the sustained NF-kappa B activity per manently induced by the virus itself in chronically HIV-infected U937 cells.(3) This resulted in only a partial inhibition of TNF- or PMA-in duced HIV replication in U1 cells, and no detectable effect on HIV rep lication in chronically infected U937 cells. This may be the first lim itation to potential antiviral effects of antioxidant therapies. Anoth er limitation is that antioxidant concentrations high enough to block NK-kappa B activation were shown to have a suppressive effect on immun e functions in vitro, because NAC and BHA blocked IL-2-induced PBMC pr oliferation. These data warrant prudence in the design of antioxidant- based therapies aimed at suppressing HIV replication.