In vitro evaluation of the effect of AZT in combination with two antioxidants and a NF-kB inhibitor.

D.RIVA, N.FERNÁNDEZ LARROSA, L.MARTÍNEZ PERALTA, F.COULOMBIÉ, S.MERSICH.

Río de Janeiro, Brasil

Conferencia; 3rd IAS CONFERENCE ON HIV PATHOGENESIS AND TREATMENT; 2005

International AIDS Society

Introduction: Reservoirs of HIV-1-latently infected cel!s might be depleted by two ways: (1) use of cytotoxie agents that eliminate the reservoir or (2) modulation of latent virus for targeting by antiviral drugs. Among (1), butylated hydroxyanisole (BHA), a synthetie antioxidant whieh interacts with phospholipid membranes and reduced glutathione (GSH), a regulator of cellular redox potential were chosen. Sulfasalazine (Sul), an inhibitor of the transcription factor NF·kB, GSH and BHA might be included in (2). The objective of this study was to investigate the action of azidothymidine (AZT), in combination with BHA, GSH or Sul, on chronical!y infeeted CD4+ T-cells. Methods: HIV·1 chronical!y infected, H9/HTLV·IIIB (H9+) and uninfected control (H9) cells were incubated in the presence of AZT or a combination of AZT with different agents, at no cytotoxic doses. After 24 hs, p24 antigen levels were assessed on cell supernatants and a cell viability assay, based on a tetrazolium salt (MTT) was perforrned. Results: Combination of AZT with BHA deereased cell viability (26%) and inereased p24 levels (22%) in H9+ cel! supernatants, as eompared to untreated control cells. Combination of AZT with GSH had no effeet on both parameters. Interestingly, the eombination of AZT with Sul reduced cell viability ofH9+ cells (31%) while p241evels diminished (18%). Conclusions: Increased cytotoxieity of AZT plus BHA could be related to a higher permeability to AZT, thus, increase of p24 (p