Enhanced immune reconstitution with albuvirtide in HIV-infected immunological non-responders.

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.

Comparison of pharmacokinetics and safety of albuvirtide in healthy subjects after intravenous drip and bolus injection.

Albuvirtide (ABT) is the first long-acting HIV fusion inhibitor developed in China, blocking the invasion of HIV-1 virus into target cells. This study aimed to compare the pharmacokinetics (PK), tolerability, and safety of ABT following a single intravenous (IV) bolus injection or intravenous drip in healthy Chinese subjects. A single-center, randomized, open-label, single-period, parallel phase I clinical trial was conducted. Thirty subjects were randomly divided into three groups in a ratio of 1:1:1. After an overnight fast, all subjects received a single dose of 320 mg ABT either by intravenous drip for 45 min (group A) or bolus injection for 0.5 min (group B), or bolus injection for 3 min (group C). ABT plasma concentrations were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Non-compartmental analysis was used to evaluate PK parameters. The median time to reach maximum concentration was 0.75 h in group A and 0.16 h in both groups B and C. Elimination half-life, mean residence time, apparent clearance, and apparent volume of distribution were similar among the three groups. The 90% confidence intervals (CI) of geometric mean ratios of PK parameters for groups B and C relative to group C were within 85-120%. All adverse events (AEs) reported in this study were mild, according to the CTCAE guidelines and the study investigator's judgement. ABT bolus injections for 0.5 min and 3 min are expected to be well tolerated and to exhibit similar PK characteristics as IV drip for 45 min, offering potential clinical benefits.

The Edwards volume ensemble in cyclically sheared granular experiments.

We experimentally investigate the Edwards volume ensemble in cyclically sheared bidisperse disks of two friction coefficients (µ ≈ 0.3 and µ → ∞) subjected to a range of shear amplitudes γm. Despite the local and global anisotropy, hysteresis, and the potential long-range correlation of the free volume, the Edwards volume ensemble surprisingly provides an excellent statistical description of disk packings in cyclically sheared systems. Our finding can be better understood from the comprehensive analysis of the geometric and statistical properties of Voronoi cells of individual particles. First, the average degrees of anisotropy of Voronoi cells are weak at both the microscopic and macroscopic scales within a range of shear amplitudes γm of up to γm = 12% regardless of the inter-particle friction coefficients µ even though the azimuthal distributions of the Voronoi cell depend on µ. Second, there is only negligible hysteresis of global compactivity and volume fluctuations. Finally, the spatial correlations of the free volume and the orientation are weakly anisotropic and short ranged for practical purposes. Both results are independent of µ. Interestingly, our free-volume statistical results are consistent with the simple physical picture that the free volume is directly proportional to the compactivity.

Turbulent-like velocity fluctuations in two-dimensional granular materials subject to cyclic shear.

We perform a systematic experimental study to investigate the velocity fluctuations in the two-dimensional granular matter of low and high friction coefficients subjected to cyclic shear of a range of shear amplitudes, whose velocity fields are strikingly turbulent-like with vortices of different scales. The scaling behaviors of both the transverse velocity power spectra ET(k) ∝ k-αT and, more severely, the longitudinal velocity power spectra EL(k) ∝ k-αL are affected by the prominent peak centered around k ≈ 2π of the inter-particle distance due to the static structure factor of the hard-particle nature in contrast to the real turbulence. To reduce the strong peak effect to the actual values of αν (the subscript 'ν' refers to either T or L), we subsequently analyze the second-order velocity structure functions of S(2)ν(r) in real space, which show the power-law scalings of S(2)ν(r) ∝ rßν for both modes. From the values of ßν, we deduce the corresponding αν from the scaling relations of αν = ßν + 2. The deduced values of αν increase continuously with the shear amplitude γm, showing no signature of yielding transition, and are slightly larger than αν = 2.0 at the limit of γm → 0, which corresponds to the elastic limit of the system, for all γm. The inter-particle friction coefficients show no significant effect on the turbulent-like velocity fluctuations. Our findings suggest that the turbulent-like collective particle motions are governed by both the elasticity and plasticity in cyclically sheared granular materials.