Background: The European AIDS Clinical Society (EACS) guidelines were revised for the 21st time in 2025, with updates covering all aspects of HIV care.

Key points of the guidelines update: The structure of the guidelines has been reorganized into two parts: Part I focuses on the management and prevention of HIV and related infections, and Part II addresses comorbidities and other relevant topics. In Part I, Version 13.0 recommends the following first-line regimens for adults with HIV-1: tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) with either lamivudine or emtricitabine (XTC), in combination with dolutegravir (DTG), bictegravir (BIC), or doravirine (DOR); or a dual therapy option consisting of XTC plus DTG. Version 13.0 introduces a completely new section on HIV-2. The preferred first-line regimens for HIV-2 include triple therapy with a second-generation integrase inhibitor: either TAF/FTC/BIC or TDF/XTC + DTG. The PrEP section has been updated to include the use of long-acting injectable antiretrovirals. Drug-drug interaction (DDI) tables have been updated to include long-acting antiretrovirals and considerations related to substance use, including drugs used to enhance or prolong sexual activity (chemsex). Tables for preferred and alternative ART regimens in children and adolescents have been updated, with particular attention to neonates. A new section on transition to adult care has also been included. The co-infections section has undergone extensive revision, especially regarding HBV, sexually transmitted infections, opportunistic infections (particularly tuberculosis, leishmaniasis, and cryptococcosis) and mpox, incorporating recent clinical trial data on tecovirimat. In Part II, Version 13.0 introduces major updates to the comorbidities section. In the cancer section, screening recommendations for anal and breast cancer have been updated. Cardiovascular and metabolic health sections have been significantly modified, reflecting recent advances and the use of statins in people with HIV. Topics such as kidney and liver complications, mental health, travel and solid organ transplantation have been thoroughly revised. New sections on sleep health and a unified substance use section have been added.

Conclusions: In 2025, the EACS Guidelines underwent a comprehensive update and restructuring. They now consist of two distinct parts and include several new sections. The recommendations are available as a free mobile app and in an interactive web format.