In vitro analysis of synergism and antagonism of different nucleoside/nucleotide analogue combinations on the inhibition of human immunodeficiency virus type 1 replication.

摘要: In this study we have developed an in vitro system to evaluate the combined effect of two NRTIs on HIV replication and assess their antagonism or synergy. Synergy was determined peripheral blood mononuclear cells (PBMCs) approach a more physiological model than T-cell lines. PBMCs were infected with full-length HIV-1 clone carrying luciferase gene as reporter. The following combinations investigated: zidovudine+stavudine (ZDV + d4T), lamivudine abacavir (3TC ABC), didanosine ddI), stavudine tenofovir (TDF 3TC), zidovudine ZDV), (d4T (ABC d4T). combining drugs evaluated quantitative method based median-effect principle Chou Talalay. A synergistic observed containing TDF ZDV d4T, d4T ddI plus 3TC. contrast, including ddI, 3TC ABC showed antagonistic inhibition viral at all levels tested. Lower also found drug that included ABC, TDF, ABC. conclusion, allows measure different replication. results suggest therapy thymidine analogues may be considered for future therapeutic options contrast clearly such us would explain virological failure clinical studies when these used.