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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.

BackgroundThe HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083.MethodsRetrospective testing included HIV testing, viral load testing, quantification of study drugs, and HIV drug resistance testing.ResultsFifty-eight infections were evaluated, including 51 incident infections (12 in CAB arm and 39 in TDF/FTC arm). In many cases (5 in CAB arm and 37 in TDF/FTC arm), infection was associated with low or unquantifiable study drug concentrations. In 4 cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral therapy, and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing.ConclusionsEarly detection of HIV infection and prompt antiretroviral therapy initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.

IntroductionThe HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083.MethodsRetrospective testing included HIV testing, viral load testing, quantification of study drugs and HIV drug resistance testing.ResultsFifty-eight infections were evaluated, including 51 incident infections (12 CAB, 39 TDF/FTC). In many cases (5 CAB, 37 TDF/FTC), infection was associated with low or unquantifiable study drug concentrations. In four cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral treatment (ART), and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing.ConclusionsEarly detection of HIV infection and prompt ART initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.

Understanding the instantaneous and creep mechanical responses of rocks subjected to the combined influence of static and dynamic loading is of great importance for designing underground works. This study developed an impact-disturbance creep loading apparatus and conducted a series of multistage impact-disturbance creep experiments on sandstones, varying static creep loads, and dynamic disturbances. The investigation analyzed specimen deformation, acoustic emission (AE) signals, and nuclear magnetic resonance (NMR) porosity changes to determine creep characteristics from microscopic damage to macroscopic failure. The experiment revealed the profound influence of dynamic disturbances on sandstone's instantaneous and creep behavior. Initially, these disturbances induce specimen densification under low creep stress but exacerbate damage propagation beyond a certain creep stress threshold. Moreover, increased dynamic disturbance energy correlates with higher creep failure strains but lower long-term specimen strengths. AE monitoring highlighted the role of dynamic disturbances in promoting tensile failure and the dominance of tensile cracks throughout the creep process. Notably, impact disturbances cause a significant increase in specimen porosity postcreep failure, especially in large pores. To capture sandstone creep behavior comprehensively under dynamic disturbance, a viscoplastic disturbance-damage creep model is proposed by integrating a disturbance-damage instantaneous element and dynamic-damage viscous element. The model can effectively describe sandstone creep behavior under dynamic disturbance conditions, offering valuable insights for underground work design. [ABSTRACT FROM AUTHOR]

With the intensification and large scale of coal mining, scraper conveyors are developing towards high power, large volume, long haul distance, and high reliability. It is more and more important to obtain the dynamic tension of the scraper chain with time‐varying loads. The purpose of this paper is to obtain the dynamic tension of scraper chains of the scraper conveyor with time‐varying loads. First, according to the structural characteristics and working environment of the scraper conveyor and the polygon effect of the sprocket, the scraper conveyor dynamic model under the action of the time‐varying loads is established by the finite unit method. Second, the load variation rule of the bearing section is explored when the scraper conveyor and shearer work together. Furthermore, the element resistance of each discrete element, the stiffness coefficient of the scraper chain, and the influence of polygonal effect of sprocket wheel are analyzed. And then, the dynamic tension of the scraper chain is obtained by the Hilber–Hughes–Taylor (HHT) method. Finally, the validity of the scraper conveyor dynamic model is verified by the example analysis and field measurement experiment. Due to the influence of heavy starting, the maximum tension of the scraper chain during the starting process is 751.6 kN, which is 12.25% higher than the tension with smooth running (669.6 kN). During the startup stage, significant impacts occur on both motors and scraper chains which may lead to damage. To protect these components effectively, control strategies such as "soft start" or no‐load start hold crucial engineering significance in achieving reliable operation of the scraper conveyor. The obtained results can provide a theoretical basis for the reliability evaluation and parameter optimization of the scraper conveyor. [ABSTRACT FROM AUTHOR]

Introduction: The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included 'universal testing and treatment' on HIV incidence in 21 communities in Zambia and South Africa during 2013-2018. The primary study endpoint was based on the results of laboratory-based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. Methods: HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. Results: HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV-positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. Conclusions: This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this arge cluster-randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided usefu data on the frequency of errors and provided more accurate data for HIV incidence estimates. Keywords: HIV incidence; seroconverters; HIV testing; community-randomized; Zambia; South Africa, (1) | INTRODUCTION Universal testing and treatment (UTT) for HIV prevention is an important component of HIV prevention programmes [1,2]. The HIV Prevention Trials Network (HPTN) 071 (PopART) trial, the [...]