We investigated the use of a system with an ingestible sensor (Proteus Digital Health Feedback system) co-encapsulated with antiretrovirals (ARVs) to measure real-time adherence. To assess the safety and impact, if any, co-encapsulation might have on ARV concentrations, we evaluated the pharmacokinetics of ARVs co-encapsulated with an ingestible sensor for eight commonly used fixed-dose combination ARVs: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC/tenofovir alafenamide (TAF); efavirenz (EFV)/FTC/TDF; abacavir (ABC)/lamivudine (3TC); dolutegravir (DTG)/ABC/3TC; rilpivirine (RPV)/TAF/FTC; elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF; and bictegravir (BIC)/FTC/TAF. The steady-state apparent peak plasma concentration (Cmax) and area under the curve (AUC) were determined from plasma concentrations measured at pre-dose, 1, 2, 4 and 6 hours post dose, and compared with literature values. A total of 49 unique patients on stable regimens for at least 12 weeks with undetectable viral loads were recruited. Cmax and AUC values were not statistically significant different from literature values for all of the formulations except the Cmax of FTC/TDF, Cmax of BIC, and the Cmax of RPV. In a subsequent evaluation of FTC/TDF and BIC/FTC/TAF using a crossover design, the geometric mean ratio (GMR) between the co-encapsulated and the un-encapsulated formulations for FTC/TDF were: FTC, 84.6% (90% CI 66.6%-107.4%) for AUC and 77.5% (60.1%-99.9%) for Cmax. For tenofovir (TFV) the GMR was 96.2% (90% CI 89.2%-103.8%) for AUC and 87.3% (64.2%-118.7%) for Cmax. The GMR for BIC (from the BIC/FTC/TAF formulation) was 98.0% (90% CI 84.5%-113.5%) for AUC and 89.9% (84.5%-95.7%) for Cmax. The observed deviation in FTC/TDF (Truvada) may be due to participant characteristics, fasted/fed conditions, and/or random variation and may warrant further investigations with a larger sample size. These findings provide assurance for use of co-encapsulated ARVs for future HIV treatment-adherence research.

Fibroblast growth factor (FGF) 23 is a well-known phosphaturic hormone produced mainly by bone cells to maintain phosphate and mineral homeostasis. Serum FGF23 levels are elevated in patients with chronic kidney disease (CKD), and elevated FGF23 might increase the risk of cardiovascular disease (CVD). Several reports have documented an increased incidence of risk factors for osteopenia, CKD, and CVD in people living with HIV (PLWH). However, few reports related to FGF23 in PLWH have been published. </p> Methods: Male HIV patients who presented to the outpatient clinic of Teikyo University Hospital, Tokyo, Japan, in 2015 and were treated with antiretroviral therapy (ART) for > 6 months were enrolled in the study. In addition to serum FGF23 measurements, the clinical factors assessed included age, ART regimens, and laboratory data. Spearman correlation and multiple regression analysis were performed to determine factors significantly associated with FGF23. </p> Results: In total, 67 patients were enrolled in the present study. The median age was 43.7 years, the median CD4 count was 529 cells/μL, and the median serum FGF23 level was 36.0 pg/mL. Based on correlation and multiple regression analyses, serum FGF23 levels were significantly correlated with HIV RNA > 50 copies (correlation analysis: t = 3.4259, P = 0.0011 / multiple regression analysis: P = 0.00106) or abacavir (ABC)/lamivudine (3TC) use (t = 2.8618, P = 0.0057 / P = 0.02704). </p> Conclusions: Factors significantly associated with elevated serum FGF23 levels included poor virologic control and ABC/3TC use. </p>.

Newcastle disease virus (NDV), causes huge economic loss to the poultry industry due to high mortality and morbidity. In this concept, the present study was aimed to assess the protective role of novel phosphorylated analogue ABC-1 in vivo in NDV infected chicken through the inhibition of fusion protein. Both NDV induced oxidative damage and protective role of novel phosphorylated ABC-1 was evaluated in vital organs like liver and lung of chicken. ELISA results showed protein oxidation and nitration levels were significantly raised in NDV infected tissues compared to healthy controls, whereas levels were reduced significantly (p < 0.05) in birds treated with phosphorylated compounds compared to NDV infected group alone. Additional investigation with double immunofluorescence showed that large amount of immuno co-localization and Western blot analysis also confirmed this observation through its band pattern in NDV infected birds compared to healthy birds, where as these alterations were reduced in treatment with novel phosphorylated ABC-1. The expression of fusion glycoprotein was studied by immuno co-localization, PCR and flow cytometry, results demonstrated that the novel phosphorylated analogues reduced the expression of fusion glycoprotein. These results put forth that novel phosphorylated ABC-1 protects chicken from NDV induced pathogenesis, protein oxidation/nitration and exerts potent antiviral activity.

P-glycoprotein (ABCB1), an ATP-binding-cassette efflux transporter, limits intestinal absorption of its substrates and is a common site of drug-drug interactions (DDIs). ABCB1 has been suggested to interact with many antivirals used to treat human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infections. Using bi-directional transport experiments in Caco-2 cells and a recently established ex vivo model of accumulation in precision cut intestinal slices (PCIS) prepared from rat ileum or human jejunum, we evaluated the potential of anti-HIV and anti-HCV antivirals to inhibit intestinal ABCB1. Lopinavir, ritonavir, saquinavir, atazanavir, maraviroc, ledipasvir, and daclatasvir inhibited the efflux of a model ABCB1 substrate, rhodamine123 (RHD123), in Caco-2 cells and rat-derived PCIS. Lopinavir, ritonavir, saquinavir, and atazanavir also significantly inhibited RHD123 efflux in human-derived PCIS, while possible inter-individual variability was observed in the inhibition of intestinal ABCB1 by maraviroc, ledipasvir, and daclatasvir. Abacavir, zidovudine, tenofovir disoproxil fumarate, etravirine, and rilpivirine did not inhibit intestinal ABCB1. In conclusion, using recently established ex vivo methods for measuring drug accumulation in rat- and human-derived PCIS, we have demonstrated that some antivirals have a high potential for DDIs on intestinal ABCB1. Our data help clarify the molecular mechanisms responsible for reported increases in the bioavailability of ABCB1 substrates including antivirals and drugs prescribed to treat co-morbidity. These results could help guide the selection of combination pharmacotherapies and/or suitable dosing schemes for patients infected with HIV and/or HCV.

We studied 48 children receiving abacavir-based HAART regimen, over a period of one-year for side effects and failure rates. None of the children developed hypersensitivity reaction. The CD4 count significantly improved from the time of enrolment till 12 months of therapy while the failure rate was 14.5%.