Addressing COVID-19 vaccine hesitancy in rural community pharmacies: a protocol for a stepped wedge randomized clinical trial

Background: Uptake of COVID-19 vaccines remains problematically low in the USA, especially in rural areas. COVID-19 vaccine hesitancy is associated with lower uptake, which translates to higher susceptibility to SARS-CoV-2 variants in communities where vaccination coverage is low. Because community pharmacists are among the most accessible and trusted health professionals in rural areas, this randomized clinical trial will examine implementation strategies to support rural pharmacists in delivering an adapted evidence-based intervention to reduce COVID-19 vaccine hesitancy. Methods: We will use an incomplete stepped wedge trial design in which we will randomize 30 rural pharmacies (unit of analysis) to determine the effectiveness and incremental cost-effectiveness of a standard implementation approach (consisting of online training that describes the vaccine hesitancy intervention, live webinar, and resource website) compared to adding on a virtual facilitation approach (provided by a trained facilitator in support of the delivery of the vaccine hesitancy counseling intervention by pharmacists). The intervention (ASORT) has been adapted from an evidence-based vaccine communication intervention for HPV vaccines through a partnership with rural pharmacies in a practice-based research network in seven southern US states. ASORT teaches pharmacists how to identify persons eligible for COVID-19 vaccination (including a booster), solicit and address vaccine concerns in a non-confrontational way, recommend the vaccine, and repeat the steps later if needed. The primary trial outcome is fidelity to the ASORT intervention, which will be determined through ratings of recordings of pharmacists delivering the intervention. The secondary outcome is the effectiveness of the intervention, determined by rates of patients who agree to be vaccinated after receiving the intervention. Other secondary outcomes include feasibility, acceptability, adoption, reach, and cost. Cost-effectiveness and budget impact analyses will be conducted to maximize the potential for future dissemination and sustainability. Mixed methods will provide triangulation, expansion, and explanation of quantitative findings. Discussion: This trial contributes to a growing evidence base on vaccine hesitancy interventions and virtual-only facilitation of evidenced-based practices in community health settings. The trial will provide the first estimate of the relative value of different implementation strategies in pharmacy settings. Trial registration: NCT05926544 (clinicaltrials.gov); 07/03/2023

Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052

Background: Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. Methods: Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env). Results: Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. Conclusions: We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data

Can Directionality of HIV Transmission be Predicted by Next-Generation Sequencing Data?

Background: We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission. Methods: For 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees. Results: DoT was predicted correctly for both single-pair and subtype-specific trees in 22 pairs (67%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples. Conclusions: Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT

Virologic outcomes in early antiretroviral treatment: HPTN 052

Introduction: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. Objective: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. Methods: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350–550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. Results: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. Conclusions: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention

HIV Drug Resistance in Adults Receiving Early vs. Delayed Antiretroviral Therapy: HPTN 052

Introduction: We evaluated HIV drug resistance in adults who received early vs. delayed antiretroviral therapy (ART) in a multinational trial [HIV Prevention Trials Network (HPTN) 052, enrollment 2005-2010]. In HPTN 052, 1763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm 3 (early ART arm) or 1000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pretreatment (baseline) and failure samples from participants with virologic failure. Results: HIV genotyping results were obtained for 211/249 participants (128 early ART arm and 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequency of new resistance at failure was lower among participants in the early ART arm (compared with delayed ART arm, P = 0.06; compared with delayed ART arm with ART initiation before May 2011, P = 0.032). In multivariate analysis, higher baseline viral load (P = 0.0008) and ART regimen (efavirenz/lamivudine/zidovudine compared with other regimens, P = 0.024) were independently associated with higher risk of new resistance at failure. Conclusions: In HPTN 052, the frequency of new drug resistance at virologic failure was lower in adults with early ART initiation. The main factor associated with reduced drug resistance with early ART was lower baseline viral load

`Football Remembers':The Collective Memory of Football in the Spectacle of British Military Commemoration

This article examines two major rituals of contemporary national life in the UK: association football and military commemoration. It explores the ways in which remembering is enacted and performed within UK football and how these processes are related to issues of power, agency and identity in Britain today. Employing the concepts of collective memory and spectacle, this article argues that ‘memory entrepreneurs’ have sought to embed football as ‘site of memory’ in the performance of military commemoration. It concludes that this has contributed to the transformation of military commemoration, from a ritual that is observed to a spectacle that is consumed. This paper thus contributes to emergent debates on the militarization of civilian space, the shifting nature of civil–military relations in the twenty-first century, and the role of military remembrance in the reproduction of Britishness

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype