Only HIV-positive individuals naïve to ART are enrolled in the cohort. Patients are followed up locally from the enrolment date, and pre-enrolment information is also obtained. The Icona database is a centralized resource, with a web-based manual data update application and some automated data update procedures for the largest centres. Details of the study and data

type recorded (including demographic, epidemiological, clinical and genomic entries) have been given elsewhere [19]. To be included in this analysis, patients had to have had at least one clinical visit and one determination of a marker (CD4 cell count or VL) after enrolment. Factors considered in the analysis included: calendar year intervals (considering single years in the range 1998–2008), mode of HIV transmission (heterosexual contact, male homosexual/bisexual contact, IDU, other or unknown), Tanespimycin mw year of enrolment, number of therapy switches experienced (defined as any change in any drug that occurred prior to the marker measurement used in the analysis), nadir CD4 cell count, treatment status [treated continuously with ART for ≥6 months; on ART but for <6 months; or previously exposed to ART but currently on a treatment interruption (defined as being off ART for ≥30 days with at least one clinical Lorlatinib marker measurement during the

interruption time)], region of residence (north, central, south or islands), age at enrolment, gender, nationality (Italian, non-Italian European or North American, or rest of the world), hepatitis C virus (HCV) serostatus [positive or negative antibody (Ab), or unknown], and hepatitis B virus (HBV) serostatus [positive or

negative surface antigen (sAg), or unknown]. Because of the high variability between clinical sites in the frequency of testing for hepatitis, a person was defined as coinfected with HBV or HCV if there was at least one positive Fenbendazole antigen/antibody test at any time during follow-up, as negative when all tests were negative, and as unknown when no tests were available. The response variable ‘adverse immunological prognosis’ was defined as the proportion of patients with a CD4 count ≤200 cells/μL, out of the total number of patients under active follow-up in a given year (i.e. with at least one VL or CD4 measurement available in the year); similarly, the ‘adverse virological prognosis’ was defined as the proportion of patients with a VL >50 copies/mL. For any given patient, the latest marker measurement in the year in question was used. An alternative analysis, using the whole set of markers available for a patient and calculating the proportion of viro-immunological successes as the number of successes over the total of number of measurements in the year, was also performed, with concordant results (data not shown).