Although there is evidence of the effectiveness of needle and syringe programme (NSP), opioid substitution therapy (OST) and antiretroviral therapy (ART) in reducing HIV prevalence, most Central and Eastern European sub-regions still have low or no coverage of most or all of these interventions. We conducted a modelling analysis to consider the potential impact on HIV incidence and prevalence of OST, NSP, and ART in three illustrative epidemic scenarios: Russia (St. Petersburg), Estonia (Tallinn), and Tajikistan (Dushanbe). For each intervention, we consider the coverage needed of each intervention separately or in combination to: (1) achieve a 30% or 50% relative reduction in HIV incidence or prevalence over 10 years; and (2) reduce HIV incidence to below 1% or HIV prevalence below 10% after 20 years. A sensitivity analysis for St. Petersburg considered the implications of greater or no risk heterogeneity, none or more sexual HIV transmission, like-with-like mixing, different injecting cessation rates, and assuming a lower HIV acute phase cofactor. The projections suggest that high but achievable coverage levels of NSP can result in large decreases (30%) in HIV incidence in settings with high HIV prevalence among PWID. Required coverage levels are much lower when interventions are combined or in lower prevalence settings. However, even when all three interventions are combined, the targets of reducing HIV incidence to less than 1% or prevalence to less than 10% in 20 years may be hard to achieve except in lower prevalence settings.