Self-reported adherence, data for which have been collected since July 2003, is classified according to the number of missed doses within 4 weeks prior to a cohort visit (0, 1 or >1 missed doses) as described previously [10]. Hepatitis B virus (HBV) infection was considered active if HBV surface (HBs) antigen, HBV envelope (HBe) antigen or HBV DNA was positive. HCV infection was considered active if HCV RNA was positive. For logistic regression analyses Apitolisib concentration of time trends and co-factors, we restricted the cohorts to participants who had started ART. The stably suppressed category for virological endpoints and the CD4 count

>500 copies/μL stratum for immunological endpoints were separately analysed using generalized estimating equation (GEE) models allowing repeated measures per patient. Time trends were quantified by using individual calendar years with indicator variables, and tests for trend included calendar year as a single continuous variable. EPZ015666 As the frequency of viral load determinations varied depending on the clinical status of the patient (i.e. less monitoring

during stable first-line treatments with good adherence vs. more frequent monitoring in salvage treatment situations), we only used the last viral load category or CD4 stratum per year for each individual, as most participants were seen at least once per year. The effect of the length of the interval between viral load determinations was further analysed in sensitivity analyses (see below). The following fixed covariables were included in multivariable models to assess the extent of potential confounding: sex, transmission category, ethnicity (non-White vs. White), and era of starting Montelukast Sodium ART (before 1997 vs. 1997 onwards). Time-updated covariables were age (strata: <40, 40–49, 50–59 and ≥60 years), number of new drugs in the regimen (strata:

0, 1, 2 and ≥3), use of novel drug classes [fusion inhibitors, chemokine (C-C motif) receptor 5 (CCR5) antagonists and integrase inhibitors] in the regimen, hepatitis B/C infection (active vs. inactive), and Centers for Disease Control and Prevention (CDC) stage (C vs. A or B). To account for potential reverse causality, we lagged the time-updated treatment by 1 year and considered the effect to last for 1 year. These associations are thus not depicting an immediate effect of a new drug – which is more likely to be prescribed shortly after virological failure – but rather the effect of a drug that was introduced 12–24 months prior to the current virological or immunological assessment. Time-updated information on adherence and whether the participant lives in a stable partnership were analysed in separate models limited to the years 2004–2008, because that information was not available for the first years of the study period.