between nADE and CD4+ T-cell count <200/l measured after 2 years of HAART, but could not demonstrate that PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/1977615 this association was independent from age, gender and other possible confounders. Moreover, the study included only a minority of patients whose pre-HAART CD4+ count was <200 cells/ l. The large number of patients enrolled in our study and the long follow-up provided the opportunity to specifically evaluate the risk of nADE in patients who had initiated HAART at CD4+ T-cell count <200/l and to demonstrate that it was associated with incomplete CD4 + recovery, despite virological suppression. Moreover, thank to the relatively high number of events observed, it was possible to run a reliable multivariable model and to demonstrate that the association was independent from measurable confounders. Our findings underlines the need for innovative treatment strategies aimed at improving CD4+ recovery among patients presenting to care with very low CD4+ counts and with sub-optimal immune-recovery after HAART. When change of CD4+ T-cell count at year 1 compared to pre-HAART levels, instead of the absolute CD4+ count at the same time-point, was used as a covariate, only a marginal, non-statistically significant association with serious nADE was found. Similarly, pre-HAART CD4 + counts were not associated with risk of serious nADE to a statistically significant extent. Previous studies suggested that absolute CD4+ cell count measurement at certain time points after HAART initiation is a more solid prognostic indicator of AIDS clinical progression than CD4 + change from baseline. Our Danoprevir chemical information results suggest that this could also be the case for prediction of severe, non AIDS-defining morbidities. Taken together, these findings indicate that clinically important immunological response is likely to be better defined in terms of absolute postHAART CD4+ cell counts, rather than change PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19777101 from baseline in patients with an advanced immune-depletion. Interestingly enough, patients developing a new AIDS defining event were shown to have a 2-fold increased risk to be diagnosed with a severe nADE subsequently. Therefore, the increased risk of nADE observed in INR patients could be partially due to their greater risk of developing new AIDS events. It has to be ascertained whether a condition of pre-existing immune dysfunction, immune activation or persistent inflammation predispose to both events or the occurrence of AIDS is in the causal pathway leading to nADE. In either case, our results suggest the importance of monitoring patients with AIDS on HAART for the risk of subsequent nADE events, persisting for more than 5 years notwithstanding suppression of HIV RNA induced by HAART. At the same time, although in our patients morbidity and mortality due to severe non AIDS-related events exceeded that due to AIDS-related causes, prevention of AIDS and earlier HAART remain a priority. In our cohort, positive HCV-Ab testing was associated with a greater risk of INR. Whether this effect is directly attributable to hepatitis C virus co-infection or to other associated conditions is still debated. A previous study suggested that HCV-Ab positive patients are more likely to have an incomplete CD4+ restoration, whereas others suggested that previous intravenous drug use, but not HCV co-infection, is associated with suboptimal CD4 response to HAART. Similarly, results on the 
effect of ongoing hepatitis C virus replication on CD4 + T-cell recovery are conflicting. Either way, our
