Opiate use has been documented in 36 countries in Africa, with its prevalence ranging from an estimated 2.3% of the adult population in Seychelles, to 1% in Mauritius, and 0.3% in Kenya (Ministry of Health of Seychelles, 2011; UNODC, 2014). Injecting drug use has been reported in 28 African countries, with increasing evidence of linked HIV epidemics (Bouscalliou, Evanno, Proute, Inwole, & Kanran, 2016; Kurth et al., 2015; Lepretres et al., 2015; Matiko et al., 2014; Nyandindi et al., 2014; Scheibe et al., 2016; Eluwa et al. 2013). Two scenarios characterize the diffusion of HIV among people who inject drugs (PWID) in the Sub-Saharan African region: there are countries, such as Kenya and Tanzania, that have moved from a long-established generalized HIV epidemic to a recent mixed epidemic with high HIV prevalence among key populations, including PWID; and there are concentrated HIV epidemics among PWIDs emerging in low HIV prevalence countries, such as Mauritius, Seychelles and Zanzibar. There is now wide consensus in the region that the adoption of the comprehensive package of nine evidence-informed interventions recommended by United Nations (WHO, UNODC and UNAIDS, 2012), and the United States President’s Emergency Fund for AIDS Relief (PEPFAR) tenth intervention, namely outreach, can help significantly reduce new HIV and hepatitis infections among PWID and their sexual partners. The global evidence in support of combination HIV prevention for PWID is compelling (Degenhardt et al., 2010; MacArthur, Minozzi, & Martin, 2012), and this has framed initiatives supported by PEPFAR in the region since 2010 towards fostering policy change supportive of the development of harm reduction. The combination of interventions promoted includes mutually reinforcing biomedical, behavioural, and structural interventions, which are not only evidenceinformed but rights-based as well as community-owned. Countries have begun to endorse and develop a package of HIV prevention intervention for PWIDs, including to varying extent, medically assisted therapies for treating opiate use and addiction, low threshold access to antiretroviral HIV treatment, needle and syringe distribution and exchange, sexual behaviour change communication, and community outreach. There is also a need for structural interventions to address critical social, legal, political, and environmental enablers of HIV risk. The policy environment for harm reduction has significantly improved in the region over the last five years. This has enabled