Highly-active antiretroviral therapy (HAART) has changed the clinical course of HIV infection, reducing mortality and lowering the incidence of opportunistic infections. The wide range of drugs now available has boosted the likelihood of success, but also the risk of drug interactions and adverse reactions. Some of these are expected, but others cannot be foreseen; some arise fairly promptly, but others take longer.

Controlled clinical trials, essential for drug registration, have tackled the question, but have not given full replies on how the toxicity affects the clinical management of antiretroviral therapy. There are three main reasons for this, all linked to the intrinsic limits of pre-marketing trials: one is the small numbers of patients, which means it is impossible to detect rare adverse reactions; another is the fact that the experimental protocols usually exclude subgroups of patients who in real clinical life would need the drug, and the third is that studies are normally too short for any assessment of delayed reactions.

Adequate post-marketing pharmacosurveillance systems are therefore absolutely indispensable. Active surveillance is clearly necessary, particularly of recently registered drugs, to check for unexpected events, and to assess the incidence of severe events in non-selected populations, and the long-term effects.

The SCOLTA project (Surveillance COhort Long-term Toxicity of Antiretrovirals) was set up as a pharmacosurveillance system for new antiretroviral drugs and a "sentinel" for unexpected and late adverse reactions arising during any antiretroviral treatment. This on-line recording system was established by the CISAI group (Italian coordinators for the study of allergies and HIV infection), especially for antiretroviral drugs. A special web site is available: www.cisai.info. A total of 25 infectious disease centers throughout Italy participate, with the possibility of observing about 12,000 HIV-positive patients.

This pharmacosurveillance program is divided into two sections:

A - The "Unexpected events Project" This part is based on spontaneous notification by participating centers, for all their patients taking antiretroviral therapy. The aim is to identify and assess the incidence of unexpected adverse reactions during treatment with any antiretroviral drug. Adverse reactions are defined as any response to therapy that differs in nature or severity from those described in the package insert or the marketing authorization, or is unexpected in relation to the drug's characteristics [5].

B - The "New Drugs project" This is a prospective, multicenter, observational pharmacosurveillance study involving one cohort of patients for each new drug. Adverse reactions are defined as any response that is harmful, not wanted, or unexpected, arising at the doses used for therapy in man. This definition excludes intentional or accidental poisoning and therapeutic failures (4).