Switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat in heavily antiretroviral-experienced, virologically suppressed HIV-infected adults receiving complex regimens.

OBJECTIVES: To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH). METHODS: Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)< 50 copies/mL at Week 48 (ITT). RESULTS: We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5-734.5), 24 years on ART (IQR: 15.9-27.8). The median number of pills was 4 (range: 3-10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VL < 50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters. CONCLUSIONS: Our data suggest that BIC/FTC/TAF + darunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.

Comparison of Three Renal Function Formulas for Ganciclovir/Valganciclovir Dose Individualization in CMV-Infected Solid Organ Transplantation Patients Using a Population Approach.

BACKGROUND AND OBJECTIVE: The gold standard treatment of established cytomegalovirus infection or prevention in solid organ transplantation is the intravenous administration of ganciclovir (GCV) or oral administration of valganciclovir (VGCV), both adjusted to the renal function. In both instances, there is a high interindividual pharmacokinetic variability, mainly owing to the wide range of variation of both the renal function and body weight. Therefore, accurate estimation of the renal function is crucial for GCV/VGCV dose optimization. This study aimed to compare three different formulas for estimating the renal function in solid organ transplantation patients with cytomegalovirus infection, for individualizing antiviral therapy with GCV/VGCV, using a population approach. METHODS: A population pharmacokinetic analysis was performed using NONMEM 7.4. A total of 650 plasma concentrations obtained after intravenous GCV and oral VGCV administrations were analyzed, from intensive and sparse sampling designs. Three different population pharmacokinetic models were built with the renal function given by Cockcroft-Gault, Modification of Diet in Renal Disease, or Chronic Kidney Disease EPIdemiology Collaboration (CKD-EPI) formulas. Pharmacokinetic parameters were allometrically scaled to body weight. RESULTS: The CKD-EPI formula was identified as the best predictor of between-patient variability in GCV clearance. Internal and external validation techniques showed that the CKD-EPI model had better stability and performed better compared with the others. CONCLUSIONS: The model based on the more accurate estimation of the renal function with the CKD-EPI formula and body weight as a size metric most used in the clinical practice can refine initial dose recommendations and contribute to GCV and VGCV dose individualization when required in the prevention or treatment of cytomegalovirus infection in solid organ transplantation patients.

Variations observed for insulin concentrations in an interlaboratory quality control program may be due to interferences between reagents and the matrix of the control materials.

The present study was carried out to observe the behaviour of insulin concentrations in an interlaboratory quality control program from BioRad Laboratories (Irving, CA) applied to Immulite 2000 (Diagnostics Product Corporation, Los Angeles, CA) for three control materials of Lyphocheck Immunoassay Plus Control. Insulin was measured for 261 consecutive working days in a year using a solid-phase immunometric chemiluminescent assay; likewise insulin was measured for 55 days during a period of 4 months in a pool of sera obtained from patients with insulin concentrations within the normal range of our laboratory. The results from each control material were classified in three groups according to the closeness among concentrations and time; mean concentrations were significantly different between consecutive groups for the three control materials (p<0.0001). However, no differences were observed in samples from pool sera. The variations observed in insulin concentrations of the control materials may be due to some interferences or matrix effect on the control material caused by the reagents to quantify insulin in the Immulite 2000.

Postresection parathyroid hormone and parathyroid hormone decline accurately predict hypocalcemia after thyroidectomy.

Hypocalcemia is the most frequent complication after total thyroidectomy. Parathyroid hormone (PTH) measurement has been proposed as an early predictor of this condition. Total thyroidectomy was performed in 39 patients. Hypocalcemia was present in 15 cases (38%). Patients undergoing hemithyroidectomy (n = 13) were considered control subjects not developing hypocalcemia. PTH was measured before surgery and 10 minutes after resection of the gland using a rapid (15 minutes) chemiluminescent immunometric assay. Patients developing hypocalcemia had lower calcium and postresection PTH levels and higher PTH decline than patients not developing hypocalcemia (P < .0001). PTH decline (cutoff value, 62.5%) had the better sensitivity (93.3%) for predicting hypocalcemia, allowing for a fairly safe early discharge. However, the best overall results corresponded to the combination of postresection PTH level (< or = 18 pg/mL [< or = 1.9 pmol/L]) and PTH decline (>62.5%), with a sensitivity of 90% and a specificity of 97.9%. Perioperative PTH measures can accurately predict hypocalcemia after thyroidectomy, granting the laboratory a key role in the immediate decision about calcium supplementation for patients at risk.