The objective of the current study is to describe the impact of Combination antiretroviral therapy (cART) on trends in AIDS incidence over time for selected population groups in Australia, specifically, men who have sex with men (MSM) and injecting drug users (IDUs). A modified back-projection modeling technique was used to predict the number of AIDS diagnoses without cART based on Australia’s HIV/AIDS surveillance system database. Modelled estimates indicate that since 1996, the effective cART has reduced overall AIDS cases by ~70 and ~10% among MSM and IDUs respectively. The predicted reduction in AIDS cases among IDUs aged less than 40 years was 36% while there was no reduction predicted for those aged 40 years or older. The impact of cART on AIDS diagnoses has been modest among IDUs. Late presentation, poor access to health services and barriers to uptake of cART may account for the divergence between these population groups.