HIV RNA Screening Reduces Integrase Strand Transfer Inhibitor Resistance Risk in Persons Receiving Long-Acting Cabotegravir for HIV Prevention

BACKGROUND: The HPTN 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was superior to tenofovir-disoproxil fumarate/emtricitabine for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). Integrase strand transfer inhibitor (INSTI) resistance-associated mutations (RAMs) were detected in some participants with HIV infection. We used a low viral load INSTI genotyping assay to evaluate the timing of emergence of INSTI RAMs and assessed whether HIV screening with a sensitive RNA assay would have detected HIV infection before INSTI resistance emerged. METHODS: Single-genome sequencing to detect INSTI RAMs was performed for samples with viral loads <500 copies/mL from 5 participants with previously identified INSTI RAMs and 2 with no prior genotyping results. RESULTS: Major INSTI RAMs were detected in all 7 cases. HIV RNA testing identified infection before major INSTI RAMs emerged in 4 cases and before additional major INSTI RAMs accumulated in 1 case. Most INSTI RAMs were detected early when the viral load was low and CAB concentration was high. CONCLUSIONS: When using CAB-LA PrEP, earlier detection of HIV infection with a sensitive RNA assay may allow for earlier treatment initiation with the potential to reduce INSTI resistance risk. Further studies are needed to evaluate the value and feasibility of HIV RNA testing with CAB-LA PrEP

Extended Analysis of HIV Infection in Cisgender Men and Transgender Women Who Have Sex with Men Receiving Injectable Cabotegravir for HIV Prevention: HPTN 083

HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections included 7 with CAB administration within 6 months of the first HIV-positive visit (2 with on-time injections, 3 with ≥1 delayed injection, and 2 who restarted CAB) and 11 with no recent CAB administration. Three cases had integrase strand transfer inhibitor (INSTI) resistance (2 with on-time injections and 1 who restarted CAB). Among 34 CAB infections analyzed to date, diagnosis delays and INSTI resistance were significantly more common in infections with CAB administration within 6 months of the first HIV-positive visit. This report further characterizes HIV infections in persons receiving CAB preexposure prophylaxis and helps define the impact of CAB on the detection of infection and the emergence of INSTI resistance

Labour power and labour process : contesting the marginality of the sociology of work

This article opens by suggesting that the decline in the sociology of work in the UK has been overstated; research continues, but in locations such as business schools. The continued vitality of the field corresponds with material changes in an increasingly globalized capitalism, with more workers in the world, higher employment participation rates of women, transnational shifts in manufacturing, global expansion of services and temporal and spatial stretching of work with advanced information communication technologies. The article demonstrates that Labour Process Theory (LPT) has been a crucial resource in the sociology of work, especially in the UK; core propositions of LPT provide it with resources for resilience (to counter claims of rival perspectives) and innovation (to expand the scope and explanatory power of the sociology of work). The article argues that the concept of the labour power has been critical to underpinning the sustained influence of labour process analysis

Systems analysis, modelling, simulation and signal processing aspects of co-ordinated experimental and modelling investigations of high-speed gas discharge switch breakdown behaviour

Summary form only given, as follows. The authors have been engaged in coordinated experimental, analytical, and computer modeling investigations to better characterize the early-time turn-on behavior of high-speed gas discharge switching for a selected range of operating parameters. The investigations have focused on quantifying the first few nanoseconds of plasma closing switch turn-on behavior as a function of key operational parameters (e.g., gas type, gas pressure, gap length, drive circuit impedance, etc.). Various gas species (e.g., hydrogen, nitrogen, SF6, helium) have been studied experimentally over a pressure range of 0.1-bar to 50-bar using several high-speed discharge switching test fixtures of conical configuration with differing discharge circuit impedances. The near-term objective has been to characterize, through complementary experimental measurements and modeling, the macroscopic turn-on behavior of high-speed gas closing switches under a selected range of operational conditions having practical interest. Longer-term goals of this work are to bring about I improvements in modeling, design, and operational performance of high-speed gas switches for use in ultra-fast, short-pulse-duration, low-impedance circuit applications. Under such conditions, the voltage collapse time and energy losses within the switch itself can significantly degrade overall system performance. This collaborative effort has involved the use of high-resolution 3-D time-domain electromagnetic modeling, simulation, and digital signal processing to complement and extend the available experimental data. Work has also been underway to develop and incorporate improved discharge channel physics modeling. This paper specifically describes the systems modeling, signal processing, and data analysis aspects of the investigations, and reports on results achieved to date. A related paper being submitted to this conference deals more specifically with certain aspects and recent results of the experimental investigation