Early denialist arguments held that the HIV/AIDS paradigm was flawed because it had not led to effective treatments. However, the introduction of highly active antiretroviral therapy in the mid-1990s and dramatic improvements in survival of HIV/AIDS patients reversed this argument, as these treatments were based directly on anti-viral activity and the HIV/AIDS paradigm. The development of effective anti-AIDS therapies based on targeting of HIV has been a major factor in convincing some denialist scientists to accept the causative role of HIV in AIDS.