EuroSIDA is the largest ongoing multinational prospective study on AIDS. Its prime goal is to understand how treatment affects prognosis and disease patterns. Background The treatment of AIDS has changed in recent years with the use of combinations of anti-retroviral drugs. Clinical trials provide valuable information on drug efficacy and safety, but their follow-up time is usually short, so they cannot give an overall picture of the durability of therapeutic effects, long-term drug toxicities, or the emergence of drug resistances. They do not show how regional or local differences in treatment affect the clinical outcome, nor do they reveal specific responses of certain categories of patients (intravenous drug users are excluded from such trials, even though they represent a large proportion of all AIDS patients). A complementary approach is embodied in the European Commission's Biomed project 'EuroSIDA: determination of long-term clinical outcome'. Description, impact and results EuroSIDA is a prospective study of about 8 500 AIDS patients in 60 hospitals and 20 countries (Europe and Israel). Patient data are collected at enrolment, then every six months information is taken on CD4 cell counts, viral loads, dates of treatment, the occurrence of AIDS-defining diseases, etc. Plasma samples are stored in a central repository which now contains over 10 500 samples. The project has accumulated some 17 500 person-years of patient experience. A major focus is the outcome of 'highly active anti-retroviral therapy' (HAART), the combined use of several drugs to stop replication of the AIDS virus (HIV). EuroSIDA has shown a dramatic improvement in prognosis - fewer deaths, fewer opportunistic infections as a result of higher CD4 cell counts (CD4 cells - targets of HIV - are vital components of the immune system). Changes in AIDS-related disease profiles are beginning to emerge. Surprisingly, malignant lymphoma has not declined, perhaps because it develops slowly; the study will show whether a delayed decrease occurs. But diseases considered less typical of AIDS have appeared: hepatitis, perhaps previously overshadowed by more aggressive diseases, is now on the decline, as are diabetes and cardiovascular diseases, possibly due to long-term toxic effects of HAART. Continued monitoring is needed to interpret these findings and to determine how long the favourable effects last. Another aim is to see which patients respond well to HAART, by finding markers of good/bad prognosis. One such marker is the CD4 cell count: patients with a rising count have less risk of contracting opportunistic infections, such as Pneumocystis carinii pneumonia (PCP), so it is safe to stop chemoprophylaxis. One question still to be answered is what will happen to those patients where HAART fails to suppress totally the viral load (number of virus particles in the blood)? The central repository of plasma samples is used to study resistance to treatment. This may lead to better diagnostic tests and to a way of determining the HIV subtype of all patients, to observe how this affects the clinical outcome. The project will also monitor the worrying spread of multi-drug resistance mutations in HIV. Working partnerships EuroSIDA is the successor of the Biomed project 'AIDS in Europe'. Since the venture began ten years ago, new partners have joined this well-managed, efficient and productive network. The finding that PCP chemoprophylaxis treatment can be safely stopped in patients with a rising CD4 count has even influenced US guidelines on AIDS treatment, and the network, which presents abstracts at all major conferences on HIV, is now a powerful tool for addressing new AIDS-related issues as they arise.