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Background: In spite of the availability of international guidelines, HIV prevention and management of care in prison is still unsatisfactory in many countries. Factors affecting the quality of HIV prevention policies in prison have not yet been elucidated. The present study had two aims: i) to assess national HIV prevention policies in prison in a selected group of countries; and ii) to determine which factors influenced such policies at the country level., Methods: HIV prevention policies in prison were reviewed comparatively in Moldova, Hungary, Nizhnii Novgorod region of the Russian Federation, Switzerland and Italy. The review of HIV prevention policies in prison was conducted through interviews with government officials, non-governmental organizations, professionals involved in this field, and visits to selected prisons. Information on the health of prisoners, including tuberculosis, sexually transmitted diseases, and other infectious diseases has also been collected., Results: The results indicated that all countries had adopted a policy, irrespective of the burden of HIV infection in the prison system. The content of the policy mirrored the philosophy and strategies of HIV prevention and care in the community. The 1993 WHO Guidelines were fully implemented only in one country out of four (Switzerland), and partially in two (Italy and Hungary)., Conclusions: A greater effort aimed at dissemination of information, provision of technical know-how and material resources could be the answer to at least part of the problems identified. In addition, greater national and international efforts are needed to stimulate the debate and build consensus on harm reduction activities in prison.