European HIV observational research has provided important insights into benefits and risk from antiretroviral therapy, and impact on health from co-infections, co-morbidities and lifestyle. Quantification of care performance indicators and benchmarking of clinics quality of care has allowed focus-points where to improve care. Novel data collecting and analytic tools provide a basis for creating a version 2 of European HIV observational research infrastructure, able to continue to fulfill these objectives. The creation of lakes of relevant original data (incl. patients own generated) will allow for the introduction of clinical applications derived from artificial intelligence. Conditioned on appropriate data protection/governance, such infrastructure can be used both for routine clinical care handling and for research.