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Background: Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype. Methods: We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve). Results: Most definitions classify ∼1% as ECs with median HIV-RNA 43–903 copies/ml and median CD4>500 cells/mm3. Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements <75 copies/ml with follow-up≥ six months, or with 90% of measurements <400 copies/ml over ≥10 year follow-up preformed best overall. Individuals thus defined were less likely to progress to endpoint (hazard ratios ranged from 12.5–19.0 for non-ECs compared to ECs). Conclusions: ECs are rare, less likely to progress to clinical disease, but may eventually lose control. We suggest definitions requiring individuals to have consecutive undetectable HIV-RNA measurements for ≥ six months or otherwise with >90% of measurements <400 copies/ml over ≥10 years be used to define this phenotype. [ABSTRACT FROM AUTHOR]

Introduction After achieving undetectable HIV-RNA on cART, on cessation, HIV-RNA rebounds to pre-treatment values for the majority due to the presence of an inaccessible viral reservoir. There is some evidence that cART during primary HIV infection (PHI) limits the reservoir size, optimizing the chance of maintaining viral control off cART. Data are required to predict possible viral controllers for treatment interruption following cART. This analysis aims to investigate the effect of cART duration and the rate of viral blips while on cART initiated in PHI, and other factors on maintaining viral control for those stopping cART. Material and Methods Using CASCADE data on HIV seroconverters, we characterized virologic blip (viral suppression on cART followed by a single HIV-RNA above a blip threshold and a subsequent measure below the threshold without cART change) rates for those starting cART within six months of seroconversion (SC). Using Cox models, we examined the effect of the following factors on time to virologic rebound (HIV-RNA>1000) after cART stop: cART duration, severity/rate of blips on cART, time from SC to cART start, cART class, SC year, SC age, CD4 at cART start/stop, sex and HIV risk group. Results The 660 individuals initiating cART in PHI were mostly male (91%), seroconverting between 1995 and 2012, with a median (IQR) age of 34 (29, 41) years mostly infected through sex between men (73%). Median cART duration was 14.8 (7.0, 31.7) months initiated at a median 1.9 (0.5, 3.9) months post SC. 13 (11, 16), 9 (7, 11), 6 (5, 9) and 7 (6, 10)% of individuals experienced blips >50, 100, 200 and 400 copies/mL, respectively. Of those who experienced blips, most (77-90%, depending on blip threshold) experienced just one. Among 250 individuals with undetectable HIV-RNA at cART stop, median time to rebound was 1.6 (0.30, 5.8) months. Time on cART was the only factor independently associated with control after stopping, HR for rebound=0.91 (0.86, 0.98) per extra six months spent on cART, HR for ever blipping >400 copies/mL while on cART=0.88 (0.40, 1.93). Conclusions Blips occur in about 10% of individuals who initiate cART in PHI, most of who experience only one blip, but was not predictive of subsequent virologic rebound. Increasing time spent on cART initiated in PHI could increase time of virological suppression after cART stop. [ABSTRACT FROM AUTHOR]

Objectives: ICU admission delays can negatively affect patient outcomes, but emergency department volume and boarding times may also affect these decisions and associated patient outcomes. We sought to investigate the effect of emergency department and ICU capacity strain on ICU admission decisions and to examine the effect of emergency department boarding time of critically ill patients on in-hospital mortality.Design: A retrospective cohort study.Setting: Single academic tertiary care hospital.Patients: Adult critically ill emergency department patients for whom a consult for medical ICU admission was requested, over a 21-month period.Interventions: None.Measurements and Main Results: Patient data, including severity of illness (Mortality Probability Model III on Admission), outcomes of mortality and persistent organ dysfunction, and hourly census reports for the emergency department, for all ICUs and all adult wards were compiled. A total of 854 emergency department requests for ICU admission were logged, with 455 (53.3%) as "accept" and 399 (46.7%) as "deny" cases, with median emergency department boarding times 4.2 hours (interquartile range, 2.8-6.3 hr) and 11.7 hours (3.2-20.3 hr) and similar rates of persistent organ dysfunction and/or death 41.5% and 44.6%, respectively. Those accepted were younger (mean ± SD, 61 ± 17 vs 65 ± 18 yr) and more severely ill (median Mortality Probability Model III on Admission score, 15.3% [7.0-29.5%] vs 13.4% [6.3-25.2%]) than those denied admission. In the multivariable model, a full medical ICU was the only hospital-level factor significantly associated with a lower probability of ICU acceptance (odds ratio, 0.55 [95% CI, 0.37-0.81]). Using propensity score analysis to account for imbalances in baseline characteristics between those accepted or denied for ICU admission, longer emergency department boarding time after consult was associated with higher odds of mortality and persistent organ dysfunction (odds ratio, 1.77 [1.07-2.95]/log10 hour increase).Conclusions: ICU admission decisions for critically ill emergency department patients are affected by medical ICU bed availability, though higher emergency department volume and other ICU occupancy did not play a role. Prolonged emergency department boarding times were associated with worse patient outcomes, suggesting a need for improved throughput and targeted care for patients awaiting ICU admission. [ABSTRACT FROM AUTHOR]