Overall, as expected, patients infected via homosexual contact showed the best viro-immunological outcomes and were differentiated significantly from patients infected via other routes. The estimate of the proportion of patients with undetectable viraemia in the absence of therapy is consistent with those obtained in other studies of the natural history of HIV infection in elite controllers [24]. In our analysis, the percentage of patients with unsuppressed VL was high and stable over time in ART-naïve patients and in patients on ART interruption.

As to the main analysis, we opted to show the trend in the prevalence of patients with an adverse immunological profile over time INCB024360 in the whole study population regardless of current ART use; we believe that such an analysis is crucial as it allows the detection of potential signals of failure in clinical care or access to care. For example, the high proportion of patients with a CD4 count ≤200 cells/μL in recent

years may have been attributable to several factors such as late presentation, buy C59 wnt or a delay in ART initiation until the CD4 cell count was already below the currently recommended level for starting ART. However, it is unlikely that late presentation could have a major role in explaining these findings as results were similar when we restricted the analysis to patients who had been in follow-up for ≥12 months prior to the CD4 cell count/VL measurement used from in

the analysis. The apparent increase in the risk of a poor prognosis in 2008 is likely to be driven by a larger proportion of newly enrolled patients about to start ART and for whom there was a delay in data reporting. Indeed, the same trend was not seen in the subset of patients who had been receiving ART for ≥6 months. Regarding the possible effect of age on the risk of having an adverse CD4 cell count/VL prognosis, older patients were at increased risk of having a low CD4 cell count and at a reduced risk of having a detectable VL. This finding may be explained by the fact that older patients tend to be more adherent and therefore they may experience better virological responses, but also, for a given VL, older patients are less likely to show a recovery in CD4 cell count because of possible reductions in thymic function and the production of naïve T cells [25]. Regarding the effect of other factors, most analyses indicated that patients living in the north of Italy had an increased risk of a poor virological prognosis and a reduced risk of a poor immunological prognosis, compared with patients with residence in central Italy, while patients in the south had increased risks in both categories. Coinfection with HCV showed a strong association with the risk of immunological failure, and yet was not significantly associated with VL outcomes. No apparent association with HBV coinfection was found for either outcome.