Faculty Bibliography

Introduction/UNASSIGNED:A comprehensive assessment of liver disorders was conducted among people living with HIV (PLWH) on a new antiretroviral regimen based on common core agents. Methods/UNASSIGNED:cohort were included if they had ⩾1 liver chemistry test performed both within 12 months before regimen start and over follow-up. Liver disorders were defined as a diagnosis of drug-induced liver injury (DILI) or moderate/severe liver chemistry elevations (LCE). History of liver disorders experienced within 12 months of initiation was summarized. Liver disorders occurring during follow-up were described as prevalent (all disorders) or incident (disorders occurring among PLWH without a history of liver disorders or advanced liver fibrosis). Results/UNASSIGNED:Out of 16,024 PLWH, 38% initiated DTG, 43% EVG, 5% RAL, and 14% DRV. EVG users were younger and had a lower likelihood of comorbidities or lipid-lowering agent use than DTG users. EVG users were significantly less likely to have a history of moderate/severe LCE or to have prevalent moderate LCE. RAL users were older and had a higher likelihood of comorbidities or lipid-lowering agent use than DTG users. RAL users were significantly more likely to have a history of advanced liver fibrosis and prevalent moderate/severe LCE during follow-up. DRV users were older and had a lower likelihood of lipid-lowering agent use than DTG users. There was no difference in history of LCE, nor in prevalent or incident LCE between DRV and DTG users. No DILI diagnoses were recorded. Discontinuation following a liver disorder was rare (<1%) across all groups. Conclusion/UNASSIGNED:While PLWH with comorbidities may have been channeled away from EVG and toward DTG and RAL, the incidence of moderate/severe LCE did not differ between DTG and EVG, RAL, and DRV. Plain language summary/UNASSIGNED:cohort, which provides anonymous patient-level clinical data from electronic health records. People living with HIV (PLWH) who were starting a new HIV treatment regimen that included one of four common HIV drugs were included in this study. Liver disorders included drug-induced liver injury (DILI) and moderate or severe liver chemistry elevations. History of a disorder was defined as liver disorders that occurred before starting the new treatment. Prevalent disorders were those that occurred after starting the new treatment in the whole population. Incident disorders were those that occurred after starting the new treatment, but only among PLWH without any history of liver disorders.Out of 16,024 PLWH, 38% initiated dolutegravir (DTG), 43% elvitegravir (EVG), 5% raltegravir (RAL), and 14% darunavir (DRV). EVG users were younger and less likely to have other diseases or use cholesterol lowering drugs compared to DTG users. They were also less likely to have a history of moderate/severe liver chemistry elevations or to have prevalent moderate liver chemistry elevations. RAL users were older and more likely to have other diseases or use cholesterol lowering drugs compared to DTG users. They were also more likely to have prevalent moderate/severe liver chemistry elevations than DTG users. DRV users were older and less likely to use cholesterol lowering agents compared to DTG users. There was no difference in history of liver chemistry elevations, or in prevalent, or incident liver chemistry elevations between DRV and DTG users. There were no DILI diagnoses and discontinuation of treatment following liver disorders was rare across all groups. Overall, the incidence of liver disorders after starting a new HIV treatment regimen did not differ between four common antiretroviral drugs.

BACKGROUND:Researchers must often rely on creatinine measurements to assess kidney function because direct glomerular filtration rates (GFR) and cystatin-c are rarely measured in routine clinical settings. However, HIV treatments often include dolutegravir, raltegravir, rilpivirine or cobicistat, which inhibit the proximal tubular secretion of creatinine without impairing kidney function, thus leading to measurement bias when using creatinine-based estimated GFR (eGFR). We developed eGFR correction factors to account for this potential bias. METHODS:(multivariate Cox proportional hazards models) were estimated with and without eGFR correction. RESULTS:compared to efavirenz. CONCLUSIONS:With increasing use of agents that inhibit tubular creatinine secretion, artificially low eGFR values could lead to erroneous conclusions in studies of HIV treatment and kidney outcomes measured with creatinine-based eGFR equations. Sensitivity analyses assessing the potential magnitude of bias arising from creatinine secretion inhibition should be performed.

Background: Patients with respiratory failure who require prone positioning are not considered good candidates for PD due to the concerns for increased intra-abdominal pressure, impaired diaphragmatic movement, and leaking of peritoneal fluid. We addressed the COVID-related AKI (CRAKI) surge for renal replacement therapy (RRT) by initiating an acute PD program at Bellevue Hospital including prone patients.
Method(s): All patients were in the ICU with COVID related hypoxic respiratory failure and acute kidney injury (AKI). 6/35 patients who received PD were treated for 16 hours per day in the prone position to improve oxygenation. The mean age was 54.6. The average BMI was 35.5. Patients were on mechanical ventilation 12-33 days. 3/6 patients were on CVVH however, switched to PD due to clotting. Patients were on PD for an average of 9.3 days. All PD catheters were placed at the bedside using an open cut down technique. PD was started the same day using manual exchanges. Dwell volume was gradually increased to 2 L. Exchanges were performed q1h while supine and q2h while prone, a total of 4-6 exchanges/day. The PD team coordinated timing with the prone team and ICU nurses to allow the continuation of the PD treatment. Patients were monitored clinically for abdominal distention and changes in respiratory mechanics.
Result(s): All 6 patients remained on PD for the duration of the hospitalization. There were no incidences of bowel injury, hemorrhage, exit-site infections, or peritonitis. None of the patients had any catheter malfunction. Leaking was addressed with temporarily reducing the dwell volume. Patients experienced slow draining which was due to kinking of the tubing during prone positioning. All patients were able to continue receiving PD without interruptions. Either no change or improvement in ABG and ventilator settings was noted after prone positioning and PD.
Conclusion(s): Due to COVID related surge, we saw a significant number of patients in the ICU with severe acute respiratory failure requiring prone positioning who also developed AKI requiring RRT. We were able to successfully provide acute PD in ventilator-dependent prone patients suffering from CRAKI. This required a team effort and some modifications in the conventional PD prescription. (Figure Presented)