This thesis aims to address a major knowledge gap in understanding the epidemiology of HIV infection among people who inject drugs (PWID) in the Middle East and North Africa (MENA) by 1) assessing HIV epidemic state, 2) estimating HIV epidemic potential using hepatitis C virus (HCV) prevalence, and 3) estimating HIV incidence and impact of interventions on incidence. Methods included systematic review and data synthesis, mathematical modelling, and ecological analysis of systematic review data. There was evidence of HIV epidemics among PWID in at least one-third of countries, most being emerging concentrated epidemics with HIV prevalence of about 10-15%. The overall high injecting risk environment suggests potential for further spread. Mathematical modelling indicated, across a range of HCV prevalence, overall acceptable precision in predicting endemic HIV prevalence among PWID. Ecological analysis on PWID MENA data also indicated a positive, statistically significant association between HCV and HIV endemic prevalence. Of nine MENA countries with data, five have high and three medium HIV epidemic potential, based on current HCV prevalence. The estimated HIV incidence rate among PWID ranged between 0.7% per person-year (ppy) and 7.8% ppy. Further, substantial number of HIV infections in the general population were estimated to be due to the dynamics of injecting drug use, namely among ex-PWID and sexual partners of current/ex-PWID. It was predicted that scale-up of antiretroviral therapy and harm reduction services could avert up to 90% and 70% of incident infections among PWID and their sexual partners, respectively. In conclusion, this thesis identified recent emerging HIV epidemics with high HIV incidence rates among PWID in multiple MENA countries. A novel method for estimating HIV epidemic potential using current HCV prevalence was demonstrated. In MENA, further HIV epidemic growth among PWID is predicted in most countries. Scale-up of HIV/drug interventions is needed to halt the growing epidemics.