The effects of the oligonucleotides on HCV replication are shown on the y-axis

BsAg, hepatitis B surface antigen; HCV-Ab, hepatitis C virus antibodies; HIV, human immunodeficiency virus; INR, immunological non-responders; IR, Immunological responders; NNRTI, non-nucleoside reverse Varlitinib supplier transcriptase inhibitor; PI, protease inhibitor. 1 2 The first model was adjusted for age and gender. The second model was adjusted for age, gender, intravenous drug use as route of HIV transmission, pre- HAART CD4+ T-cell count, occurrence of AIDS-defining events and immunological response. Occurrence of AIDS-defining event during follow-up was considered as time-dependent variable. Estimates for HCV-Ab positivity were not adjusted for intravenous drug PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19778700 use as route of HIV transmission, due to high correlation. doi:10.1371/journal.pone.0124741.t003 nADE either in univariable or in multivariable Cox regression analysis. Predictors of death, AIDS-defining and serious non AIDS-defining events Similar results were obtained when the composite end-point of death, AIDS-defining and serious nADE PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19778733 was used as outcome measure. Using multivariable Cox regression analysis, the following variables were associated with increased risk of clinical progression: INR at year 1, having experienced a previous AIDS-defining event, HCV-Ab positivity. Conversely, higher CD4+ change at year 1, compared with baseline, resulted to be borderline protective. Results of this analysis are shown in 9 / 15 Risk of Severe Non-AIDS Events among Immunological Non-Responders List of abbreviations: AIDS, acquired immunodeficiency syndrome; CI, confidence interval; HAART, highlyactive antiretroviral treatment; HBsAg, hepatitis B surface antigen; HCV-Ab, hepatitis C virus antibodies; HIV, human immunodeficiency virus; INR, immunological non-responders; IR, Immunological responders; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor. 1 The first model was adjusted for age and gender. 2 The second model was adjusted for age, gender, intravenous drug use as route of HIV transmission, pre- HAART CD4+ T-cell count, occurrence of AIDS-defining events and immunological response. Occurrence of AIDS-defining event during follow-up was considered as time-dependent variable Estimates for HCV-Ab positivity were not adjusted for intravenous drug use as route of HIV transmission, due to high correlation. doi:10.1371/journal.pone.0124741.t004 Discussion Notwithstanding efforts to promote early HIV testing, 20 to 40% of patients entering in care for HIV in Western Countries present with advanced HIV disease, i.e. with a CD4+ count below 200 cells/L. Failure to restore CD4+ count above this threshold, despite virological effective HAART, is a relatively common finding, which has been associated with increased risk of AIDS progression and death. Whether a lack of short-term CD4+ increase, despite suppression of HIV replication, is also associated with a greater risk of non AIDS-related morbidities is still unclear. In our cohort, failure to increase CD4+ T-cell count from below to more than 200 cells/l after 1 year of effective HAART increased the subsequent risk of severe non AIDS-related event by 65%. These results are in agreement with a recent study that demonstrated that patients unable to restore their CD4+ count to >200 cells/l after 3 years of viral suppression run a higher risk of death due to non AIDS-defining causes. This study, however, could not explore the possible association between INR and non-fatal events. A previous study had suggested an association