2.2 Hepatitis B). Proportion of patients with CD4 cell count <350 cells/μL not on ART. Proportion of patients with CD4 Selleck NVP-BKM120 cell count >350 cells/μL and

an indication to start ART not on ART. To date there have been no published randomized trials that directly assess whether treatment-naïve people with higher CD4 cell counts should initiate ART immediately rather than defer until the CD4 cell count falls to ≤350 cells/μL; while the START trial is addressing this question, results are not expected until 2015. Only one trial [1] has randomized people with a CD4 cell count >350 cells/μL, but this used a comparator arm of delay of initiation of ARVs until the CD4 cell count has fallen below 250 cells/μL, and thus is likely to overestimate the apparent

benefits of immediate treatment compared with starting at <350 cells/μL. There have been a number of observational studies that have attempted to address this issue [2-9], which have produced conflicting findings. Some of these studies have failed to take into account the lead time between an individual's CD4 cell count falling below the threshold for treatment and the date of starting treatment [8]; as this may introduce serious bias into treatment comparisons, these results do not resolve the question whether it is better to start ART at higher CD4 cell counts. Where studies have used methods that take lead time into account, the statistical methods used are novel and different approaches Erastin purchase have been used. The analyses reached substantially different

conclusions on the mortality benefits of early ART initiation in people with a CD4 cell count >350 cells/μL, and particularly in those with CD4 cell count >500 cells/μL. Critically, none of these methods is able fully to adjust for potential confounding, which might well be large in this scenario and could Amobarbital create a bias that is in the same direction in all studies. Thus, we do not believe that the evidence is currently sufficiently strong to recommend a change in guidelines. We recommend patients presenting with an AIDS-defining infection, or with a serious bacterial infection and a CD4 cell count <200 cells/μL, start ART within 2 weeks of initiation of specific antimicrobial chemotherapy (1B). Proportion of patients presenting with an AIDS-defining infection or with a serious bacterial infection and a CD4 cell count <200 cells/μL started on ART within 2 weeks of initiation of specific antimicrobial chemotherapy. This recommendation is largely based on the ACTG 5164 study that demonstrated fewer AIDS progressions/deaths and improved cost-effectiveness when ART was commenced within 14 days (median 12 days; IQR 9–13 days) compared with after completion of treatment for the acute infection (median 45 days; IQR 41–55 days) [1, 2].