Methods The study is based on semi-structured qualitative interviews with policy-makers and senior health care managers in two Russian regions, and a review of published and unpublished sources on health systems and HIV in Russia. Findings We identified a number of factors associated with the system's failure to address the epidemic. We argue that these factors are not unique to HIV/AIDS. The features of the wider health system within which the HIV response was set up influenced the structure and capacities of the programme, particularly its regulatory and clinical orientation; the discrepancy between formal commitments and implementation; the focus on screening services; and problems with scaling up interventions targeting high-risk groups. Discussion The system-programme interplay is as important in middle-income countries as in poorer settings. An advanced health care infrastructure cannot protect health systems from potential failures in the delivery of vertical programmes. The HIV response cannot be effective, efficient and responsive to the needs of the population if the broader health system does not adhere to the same principles. Strengthening HIV responses in post-Soviet societies will require improvements in their wider health systems, namely advocacy of prevention for high-risk populations, reallocation of resources from curative towards preventive services, building decision-making capacities at the local level, and developing better working environments for health care staff.