Estimating the costs and perceived benefits of oral pre-exposure prophylaxis (PrEP) delivery in ten counties of Kenya: a costing and a contingent valuation study.

Background: Kenya included oral PrEP in the national guidelines as part of combination HIV prevention, and subsequently began providing PrEP to individuals who are at elevated risk of HIV infection in 2017. However, as scale-up continued, there was a recognized gap in knowledge on the cost of delivering oral PrEP. This gap limited the ability of the Government of Kenya to budget for its PrEP scale-up and to evaluate PrEP relative to other HIV prevention strategies. The following study calculated the actual costs of oral PrEP scale-up as it was being delivered in ten counties in Kenya. This costing also allowed for a comparison of various models of service delivery in different geographic regions from the perspective of service providers in Kenya. In addition, the analysis was also conducted to understand factors that indicate why some individuals place a greater value on PrEP than others, using a contingent valuation technique. Methods: Data collection was completed between November 2017 and September 2018. Costing data was collected from 44 Kenyan health facilities, consisting of 23 public facilities, 5 private facilities and 16 drop-in centers (DICEs) through a cross-sectional survey in ten counties. Financial and programmatic data were collected from financial and asset records and through interviewer administered questionnaires. The costs associated with PrEP provision were calculated using an ingredients-based costing approach which involved identification and costing of all the economic inputs (both direct and indirect) used in PrEP service delivery. In addition, a contingent valuation study was conducted at the same 44 facilities to understand factors that reveal why some individuals place a greater value on PrEP than others. Interviews were conducted with 2,258 individuals (1,940 current PrEP clients and 318 non-PrEP clients). A contingent valuation method using a "payment card approach" was used to determine the maximum willingness to pay (WTP) of respondents regarding obtaining access to oral PrEP services. Results: The weighted cost of providing PrEP was $253 per person year, ranging from $217 at health centers to $283 at dispensaries. Drop-in centers (DICEs), which served about two-thirds of the client volume at surveyed facilities, had a unit cost of $276. The unit cost was highest for facilities targeting MSM ($355), while it was lowest for those targeting FSW ($248). The unit cost for facilities targeting AGYW was $323 per person year. The largest percentage of costs were attributable to personnel (58.5%), followed by the cost of drugs, which represented 25% of all costs. The median WTP for PrEP was $2 per month (mean was $4.07 per month). This covers only one-third of the monthly cost of the medication (approximately $6 per month) and less than 10% of the full cost of delivering PrEP ($21 per month). A sizable proportion of current clients (27%) were unwilling to pay anything for PrEP. Certain populations put a higher value on PrEP services, including: FSW and MSM, Muslims, individuals with higher education, persons between the ages of 20 and 35, and households with a higher income and expenditures. Discussion: This is the most recent and comprehensive study on the cost of PrEP delivery in Kenya. These results will be used in determining resource requirements and for resource mobilization to facilitate sustainable PrEP scale-up in Kenya and beyond. This contingent valuation study does have important implications for Kenya's PrEP program. First, it indicates that some populations are more motivated to adopt oral PrEP, as indicated by their higher WTP for the service. MSM and FSW, for example, placed a higher value on PrEP than AGYW. Higher educated individuals, in turn, put a much higher value on PrEP than those with less education (which may also reflect the higher "ability to pay" among those with more education). This suggests that any attempt to increase demand or improve PrEP continuation should consider these differences in client populations. Cost recovery from existing PrEP clients would have potentially negative consequences for uptake and continuation.

Scholarship of Drug Information and Library Sciences Instruction in North American Pharmacy Education: A Systematic Review of English-Language Research.

OBJECTIVES: This study aimed to characterize the scholarship of teaching and learning specific to drug information and library sciences (DILS) in pharmacy education and provide a comprehensive, evidence-based resource for faculty, detailing published practices for content delivery and scholarly research gaps. FINDINGS: Systematic searches of PubMed, Embase, International Pharmaceutical Abstracts, Educational Resources Information Center, Scopus, Library Literature & Information Science Full Text, and Library, Information Science & Technology Abstracts were conducted from January 1997 through early February 2022. Included studies were published in English, involved DILS content, were specific to pharmacy education, were original research, and were conducted in North America. The review excluded abstract-only records and studies that did not include learners (ie, pharmacy students and residents) as participants. Duplicate records were removed. After screening and review, 166 articles met the eligibility criteria, 60% of which (n = 100/166) were published in the last 10 years. Most studies focused on literature evaluation (45/166, 27%), fundamentals of drug information (43/166, 25%), evidence-based medicine (21/166, 13%), and resource utilization (21/166, 13%). Studied learners were mainly pharmacy students (77%), and 82% of research included authors who were pharmacists, whereas 14% included librarians. Assessment techniques used primarily focused on student perception (61/166, 37%), followed by summative assessment (46/166, 28%), other (25/166, 15%), and formative assessment (18/166, 11%). SUMMARY: This article presents a systematically identified collection of North American literature examining the education in DILS of pharmacy learners. Areas for continued research of DILS content include evaluating underrepresented educational domains (ie, systematic approach, response development and provision, literature searching, study design), using librarians more in scholarship of teaching and learning research, and using formative and summative assessments as outcomes.

Whey Protein Supplementation and Type 2 Diabetes Mellitus Risk Factors: An Umbrella Systematic Review of Randomized Controlled Trials.

Emerging research suggests whey protein (WP) supplementation may modify type 2 diabetes mellitus (T2DM) risk factors, including glucose control. As systematic reviews and/or meta-analyses of randomized controlled trials (RCTs) gain importance in nutrition literature, we conducted an umbrella systematic review to chronicle published systematic reviews and/or meta-analyses of RCTs pertinent to WP supplementation and T2DM modifiable risk factors. This review was conducted in accordance with Preferred Reporting Items for Overviews of Reviews standards. Potentially eligible articles were identified via a systematic search of 5 electronic health research databases (PubMed, Cochrane Library, CINAHL [EBSCO], Scopus, and SPORTDiscus [EBSCO]). Included articles were assessed for quality using the "A MeaSurement Tool to Assess systematic Reviews 2" critical appraisal tool. Thirteen articles, representing 109 unique RCTs, of the 2205 identified articles met the inclusion criteria. Nine articles (69%) were deemed high quality, 2 (15%) moderate quality, and 2 (15%) low quality. Findings from this umbrella review of 13 systematic reviews, including 12 meta-analyses, suggest WP may lower hemoglobin A1c, homeostasis model assessment of insulin resistance, and fasting insulin in groups classified as overweight/obese or at risk for or with metabolic syndrome; blood triglycerides in groups classified as overweight/obese or at risk for or with metabolic syndrome; and blood pressure in groups classified as overweight/obese. WP did not differentially affect C-reactive protein, body weight, body mass index, or waist circumference, nor did it adversely affect any T2DM risk factors. Insufficient evidence precluded assessing the influence of WP on glucose control-related outcomes in groups classified at lower risk for T2DM. Information regarding WP dose, duration, or types was insufficient to draw conclusions. Collectively, evidence suggests WP supplementation may improve multiple clinical indicators of glucose control, along with triglycerides and blood pressure, in groups of adults at increased risk of developing T2DM.

PIF4 enhances the expression of SAUR genes to promote growth in response to nitrate.

Nitrate supply is fundamental to support shoot growth and crop performance, but the associated increase in stem height exacerbates the risks of lodging and yield losses. Despite their significance for agriculture, the mechanisms involved in the promotion of stem growth by nitrate remain poorly understood. Here, we show that the elongation of the hypocotyl of Arabidopsis thaliana, used as a model, responds rapidly and persistently to upshifts in nitrate concentration, rather than to the nitrate level itself. The response occurred even in shoots dissected from their roots and required NITRATE TRANSPORTER 1.1 (NRT1.1) in the phosphorylated state (but not NRT1.1 nitrate transport capacity) and NIN-LIKE PROTEIN 7 (NLP7). Nitrate increased PHYTOCHROME INTERACTING FACTOR 4 (PIF4) nuclear abundance by posttranscriptional mechanisms that depended on NRT1.1 and phytochrome B. In response to nitrate, PIF4 enhanced the expression of numerous SMALL AUXIN-UP RNA (SAUR) genes in the hypocotyl. The growth response to nitrate required PIF4, positive and negative regulators of its activity, including AUXIN RESPONSE FACTORs, and SAURs. PIF4 integrates cues from the soil (nitrate) and aerial (shade) environments adjusting plant stature to facilitate access to light.

Allogeneic haematopoietic cell transplants as dynamical systems: influence of early-term immune milieu on long-term T-cell recovery.

Objectives: Immune recovery following haematopoietic cell transplantation (HCT) functions as a dynamical system. Reducing the duration of intense immune suppression and augmenting antigen presentation has the potential to optimise T-cell reconstitution, potentially influencing long-term outcomes. Methods: Based on donor-derived T-cell recovery, 26 patients were adaptively randomised between mycophenolate mofetil (MMF) administered for 30-day post-transplant with filgrastim for cytokine support (MMF30 arm, N = 11), or MMF given for 15 days with sargramostim (MMF15 arm, N = 15). All patients underwent in vivo T-cell depletion with 5.1 mg kg-1 antithymocyte globulin (administered over 3 days, Day -9 through to Day -7) and received reduced intensity 450 cGy total body irradiation (3 fractions on Day -1 and Day 0). Patients underwent HLA-matched related and unrelated donor haematopoietic cell transplantation (HCT). Results: Clinical outcomes were equivalent between the two groups. The MMF15 arm demonstrated superior T-cell, as well as T-cell subset recovery and a trend towards superior T-cell receptor (TCR) diversity in the first month with this difference persisting through the first year. T-cell repertoire recovery was more rapid and sustained, as well as more diverse in the MMF15 arm. Conclusion: The long-term superior immune recovery in the MMF15 arm, administered GMCSF, is consistent with a disproportionate impact of early interventions in HCT. Modifying the 'immune-milieu' following allogeneic HCT is feasible and may influence long-term T-cell recovery.

Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5Δ32/Δ32) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV+, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.5 years after stopping ART, in other cases, it was insufficient without protection of engrafting cells afforded by CCR5-deficiency, as CCR5-tropic virus spread to donor CD4+ T cells despite full ART suppression. These data demonstrate the individual contributions of allogeneic immunity and CCR5 deficiency to HIV cure and support defining targets of alloimmunity for curative strategies independent of HSCT.

Modulating auxin response stabilizes tomato fruit set.

Fruit formation depends on successful fertilization and is highly sensitive to weather fluctuations that affect pollination. Auxin promotes fruit initiation and growth following fertilization. Class A auxin response factors (Class A ARFs) repress transcription in the absence of auxin and activate transcription in its presence. Here, we explore how multiple members of the ARF family regulate fruit set and fruit growth in tomato (Solanum lycopersicum) and Arabidopsis thaliana, and test whether reduction of SlARF activity improves yield stability in fluctuating temperatures. We found that several tomato Slarf mutant combinations produced seedless parthenocarpic fruits, most notably mutants deficient in SlARF8A and SlARF8B genes. Arabidopsis Atarf8 mutants deficient in the orthologous gene had less complete parthenocarpy than did tomato Slarf8a Slarf8b mutants. Conversely, Atarf6 Atarf8 double mutants had reduced fruit growth after fertilization. AtARF6 and AtARF8 likely switch from repression to activation of fruit growth in response to a fertilization-induced auxin increase in gynoecia. Tomato plants with reduced SlARF8A and SlARF8B gene dosage had substantially higher yield than the wild type under controlled or ambient hot and cold growth conditions. In field trials, partial reduction in the SlARF8 dose increased yield under extreme temperature with minimal pleiotropic effects. The stable yield of the mutant plants resulted from a combination of early onset of fruit set, more fruit-bearing branches and more flowers setting fruits. Thus, ARF8 proteins mediate the control of fruit set, and relieving this control with Slarf8 mutations may be utilized in breeding to increase yield stability in tomato and other crops.

Evaluation of References Supporting Hospital Pharmacy Policies.

There is a lack of research evaluating the role of references in hospital policies. The goal of this study was to describe the type of literature used as a reference in medication policies and evaluate the agreement of the policy with evidence-based guidelines. One hundred forty-seven pharmacy owned policies met inclusion criteria; 27.2% of the policies contained references, in which tertiary literature was the most frequently cited source (90%), followed by primary (47.5%), and lastly secondary (27.5%). When references were used, all policies agreed with current guidelines. For policies without references, 3.7% disagreed with published guidelines. Disagreement with guidelines may negatively impact patient care, therefore health systems should incorporate librarians into clinical policy development and review to ensure the best available evidence is incorporated into polices.

Meat Consumption and Gut Microbiota: a Scoping Review of Literature and Systematic Review of Randomized Controlled Trials in Adults.

Emerging research indicates the importance of gut microbiota in mediating the relationship between meat intake and human health outcomes. We aimed to assess the state of available scientific literature on meat intake and gut microbiota in humans (PROSPERO, International Prospective Register of Systematic Reviews, CRD42020135649). We first conducted a scoping review to identify observational and interventional studies on this topic. Searches were performed for English language articles using PubMed, Cochrane Library, Scopus, and CINAHL (Cumulated Index to Nursing and Allied Health Literature) databases from inception to August 2021 and using keywords related to meat (inclusive of mammalian, avian, and aquatic subtypes) and gut microbiota. Of 14,680 records, 85 eligible articles were included in the scoping review, comprising 57 observational and 28 interventional studies. One prospective observational study and 13 randomized controlled trials (RCTs) were identified in adults without diagnosed disease. We included the 13 RCTs, comprising 18 comparisons, in the systematic review to assess the effects of higher and lower intakes of total meat and meat subtypes on the gut microbiota composition. The bacterial composition was differentially affected by consuming diets with and without meat or with varied meat subtypes. For example, higher meat intake tended to decrease population sizes of genera Anerostipes and Faecalibacterium, but it increased the population size of Roseburia across studies. However, the magnitude and directionality of most microbial responses varied, with inconsistent patterns of responses across studies. The data were insufficient for comparison within or between meat subtypes. The paucity of research, especially among meat subtypes, and heterogeneity of findings underscore the need for more well-designed prospective studies and full-feeding RCTs to address the relationships between and effects of consuming total meat and meat subtypes on gut microbiota, respectively.

ATM phosphorylates PP2A subunit A resulting in nuclear export and spatiotemporal regulation of the DNA damage response.

Ataxia telangiectasia mutated (ATM) is a serine-threonine protein kinase and important regulator of the DNA damage response (DDR). One critical ATM target is the structural subunit A (PR65-S401) of protein phosphatase 2A (PP2A), known to regulate diverse cellular processes such as mitosis and cell growth as well as dephosphorylating many proteins during the recovery from the DDR. We generated mouse embryonic fibroblasts expressing PR65-WT, -S401A (cannot be phosphorylated), and -S401D (phospho-mimetic) transgenes. Significantly, S401 mutants exhibited extensive chromosomal aberrations, impaired DNA double-strand break (DSB) repair and underwent increased mitotic catastrophe after radiation. Both S401A and the S401D cells showed impaired DSB repair (nonhomologous end joining and homologous recombination repair) and exhibited delayed DNA damage recovery, which was reflected in reduced radiation survival. Furthermore, S401D cells displayed increased ERK and AKT signaling resulting in enhanced growth rate further underscoring the multiple roles ATM-PP2A signaling plays in regulating prosurvival responses. Time-lapse video and cellular localization experiments showed that PR65 was exported to the cytoplasm after radiation by CRM1, a nuclear export protein, in line with the very rapid pleiotropic effects observed. A putative nuclear export sequence (NES) close to S401 was identified and when mutated resulted in aberrant PR65 shuttling. Our study demonstrates that the phosphorylation of a single, critical PR65 amino acid (S401) by ATM fundamentally controls the DDR, and balances DSB repair quality, cell survival and growth by spatiotemporal PR65 nuclear-cytoplasmic shuttling mediated by the nuclear export receptor CRM1.

Poultry Consumption and Human Health: How Much Is Really Known? A Systematically Searched Scoping Review and Research Perspective.

This scoping review was conducted to systematically search and chronicle scientific literature pertinent to poultry intake and human health. The protocol (uploaded to Open Science Framework, https://osf.io/2k7bj/) was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews guidelines. Articles with observational and experimental research, narrative and systematic reviews, and meta-analyses were included. Among 13,141 articles identified, 525 met inclusion criteria. Among these 525 articles, 212 focused on cancer morbidity and mortality; 41 on cardiovascular disease (CVD) morbidity and mortality; 52 on CVD risk factors; 32 on type 2 diabetes mellitus (T2DM) morbidity and mortality; 33 on T2DM risk factors; and 42 on body weight and body composition. An "Other" category (181 articles) included nutrient status, psychological well-being/mental health, cognition, microbiome, chronic kidney disease, nonalcoholic fatty liver disease, skin disorders, and fertility, among others. Among the 525 included articles, 366 were observational, 64 were experimental, and 76 were reviews and meta-analyses. Eighty-three percent of articles focused on adults or older adults. A paucity of research exists to support poultry as health-promoting foods, with most research only indirectly assessing poultry intake compared with other foods of interest (e.g., red meats or plant-based protein foods). No randomized controlled trials and only 1% of OBS assessed the influence of processed poultry intake on human health. In the future, the relative health effects of consuming poultry will be compared with a widening array of traditional and new protein-rich food products, necessitating the need for research to assess poultry as foods of choice. Science and health professionals, the poultry industry, and the public will benefit from new observational and experimental research to address cutting-edge scientific, public policy, and consumer topics pertinent to poultry intake and human health.

Health system opportunities and challenges for PrEP implementation in Kenya: A qualitative framework analysis.

BACKGROUND: As pre-exposure prophylaxis (PrEP) scales up in sub-Saharan Africa, governments and implementers need to understand how to best manage national programs. Kenya's national PrEP program offers an opportunity to review elements of program success within the health system and evaluate the utility of a national implementation framework. We explored health system considerations for PrEP implementation to understand how Kenya's national PrEP implementation priorities align with those of PrEP service providers, peer educators, and program or county managers. METHODS: We conducted twelve key informant interviews (KII) and nine focus group discussions (FGDs) with PrEP program and county managers (n = 12), peer educators (n = 44), and PrEP service providers (n = 48). We recruited participants across a variety of cadres and experiences with PrEP programs. KIIs and FGDs focused on PrEP service delivery and program implementation. Data were collected by trained study staff, audio recorded, translated into English, and transcribed. We used framework analysis methods to systematically apply Kenya's 2017 National PrEP Implementation Framework to the data and summarized findings according to the seven Implementation Framework domains. RESULTS: All respondents emphasized the important role of communication, coordination, training, and leadership in PrEP implementation. PrEP service providers and program and county managers highlighted the importance of efficient data collection and utilization, and improved resource allocation. Commodity security and research, while key elements of the PrEP Implementation Framework, were less commonly discussed, and research was less prioritized by respondents. Respondents highlighted the importance of coordinated PrEP service delivery across sites and programs to improve overall client experiences. CONCLUSION: In the context of a nationally-scaled PrEP program, PrEP service providers, peer educators, and program and county managers value strong leadership, close coordination of services across sites, and expedient use of data to improve strategies and services. Kenya's PrEP Implementation Framework aligns closely with the priorities of individuals involved in PrEP service delivery and management, and provides a comprehensive overview of health system considerations for effective implementation of a PrEP program at scale.

SAUR63 stimulates cell growth at the plasma membrane.

In plants, regulated cell expansion determines organ size and shape. Several members of the family of redundantly acting Small Auxin Up RNA (SAUR) proteins can stimulate plasma membrane (PM) H+-ATPase proton pumping activity by inhibiting PM-associated PP2C.D phosphatases, thereby increasing the PM electrochemical potential, acidifying the apoplast, and stimulating cell expansion. Similarly, Arabidopsis thaliana SAUR63 was able to increase growth of various organs, antagonize PP2C.D5 phosphatase, and increase H+-ATPase activity. Using a gain-of-function approach to bypass genetic redundancy, we dissected structural requirements for SAUR63 growth-promoting activity. The divergent N-terminal domain of SAUR63 has a predicted basic amphipathic α-helix and was able to drive partial PM association. Deletion of the N-terminal domain decreased PM association of a SAUR63 fusion protein, as well as decreasing protein level and eliminating growth-promoting activity. Conversely, forced PM association restored ability to promote H+-ATPase activity and cell expansion, indicating that SAUR63 is active when PM-associated. Lipid binding assays and perturbations of PM lipid composition indicate that the N-terminal domain can interact with PM anionic lipids. Mutations in the conserved SAUR domain also reduced PM association in root cells. Thus, both the N-terminal domain and the SAUR domain may cooperatively mediate the SAUR63 PM association required to promote growth.

Cytomegalovirus-vaccine-induced unconventional T cell priming and control of SIV replication is conserved between primate species.

Strain 68-1 rhesus cytomegalovirus expressing simian immunodeficiency virus (SIV) antigens (RhCMV/SIV) primes MHC-E-restricted CD8+ T cells that control SIV replication in 50%-60% of the vaccinated rhesus macaques. Whether this unconventional SIV-specific immunity and protection is unique to rhesus macaques or RhCMV or is intrinsic to CMV remains unknown. Here, using cynomolgus CMV vectors expressing SIV antigens (CyCMV/SIV) and Mauritian cynomolgus macaques, we demonstrate that the induction of MHC-E-restricted CD8+ T cells requires matching CMV to its host species. RhCMV does not elicit MHC-E-restricted CD8+ T cells in cynomolgus macaques. However, cynomolgus macaques vaccinated with species-matched 68-1-like CyCMV/SIV mounted MHC-E-restricted CD8+ T cells, and half of the vaccinees stringently controlled SIV post-challenge. Protected animals manifested a vaccine-induced IL-15 transcriptomic signature that is associated with efficacy in rhesus macaques. These findings demonstrate that the ability of species-matched CMV vectors to elicit MHC-E-restricted CD8+ T cells that are required for anti-SIV efficacy is conserved in nonhuman primates, and these data support the development of HCMV/HIV for a prophylactic HIV vaccine.

Quantitative Phase Imaging: Recent Advances and Expanding Potential in Biomedicine.

Quantitative phase imaging (QPI) is a label-free, wide-field microscopy approach with significant opportunities for biomedical applications. QPI uses the natural phase shift of light as it passes through a transparent object, such as a mammalian cell, to quantify biomass distribution and spatial and temporal changes in biomass. Reported in cell studies more than 60 years ago, ongoing advances in QPI hardware and software are leading to numerous applications in biology, with a dramatic expansion in utility over the past two decades. Today, investigations of cell size, morphology, behavior, cellular viscoelasticity, drug efficacy, biomass accumulation and turnover, and transport mechanics are supporting studies of development, physiology, neural activity, cancer, and additional physiological processes and diseases. Here, we review the field of QPI in biology starting with underlying principles, followed by a discussion of technical approaches currently available or being developed, and end with an examination of the breadth of applications in use or under development. We comment on strengths and shortcomings for the deployment of QPI in key biomedical contexts and conclude with emerging challenges and opportunities based on combining QPI with other methodologies that expand the scope and utility of QPI even further.

Adaptation and psychometric evaluation of a scale to measure oral pre-exposure prophylaxis-related stigma among key and vulnerable populations in Kenya.

INTRODUCTION: As oral pre-exposure prophylaxis (PrEP) services scale up throughout sub-Saharan Africa (SSA), clients continue to face challenges with sustained PrEP use. PrEP-related stigma has been shown to influence engagement throughout the HIV PrEP care continuum throughout SSA. Validated quantitative measures of PrEP-related stigma in SSA are of critical importance to better understand its impacts at each stage of the HIV PrEP care continuum. This study aimed to psychometrically evaluate a PrEP-related stigma scale for use among key and vulnerable populations in the context of a Kenya national PrEP programme. METHODS: As part of a larger prospective cohort study nested within Kenya's Jilinde programme, this study used baseline data collected from 1135 participants between September 2018 and April 2020. We used exploratory factor analysis to evaluate the factor structure of a PrEP-related stigma scale. We also assessed convergent construct validity of the PrEP-Related Stigma Scale by testing for expected correlations with depression and uptake of HIV services. Finally, we examined the relationship between PrEP-related stigma and key demographic, psychosocial and behavioural characteristics. RESULTS: We identified four dimensions of PrEP-related stigma: (1) interpersonal stigma, (2) PrEP norms, (3) negative self-image and (4) disclosure concerns. The scale demonstrated strong internal consistency (α = 0.84), was positively correlated with depressive symptoms and negatively correlated with uptake of HIV services. Multivariable regression analysis demonstrated associations between PrEP-related stigma and sex worker identity. CONCLUSIONS: The adapted and validated PrEP-Related Stigma Scale can enable programmes to quantify how PrEP-related stigma and its dimensions may differentially impact outcomes on the HIV PrEP care continuum, evaluate stigma interventions and tailor programmes accordingly. Opportunities exist to validate the scale in other populations and explore further dimensions of PrEP-related stigma.

Effect of pharmacy-led interventions during care transitions on patient hospital readmission: A systematic review.

BACKGROUND: The Centers for Medicare and Medicaid (CMS) established the Hospital Readmissions Reduction Program (HRRP) to reduce reimbursement payments to hospitals with excessive patient readmissions. Because of this program, hospitals have developed transitions of care (TOC) programs to improve patient outcomes. OBJECTIVES: To identify and uniformly summarize the impact of pharmacy-led TOC interventions on 30-day readmission rates since the implementation of CMS HRRP. METHODS: This study followed an a-priori protocol that was registered to International Prospective Register of Systematic Reviews. A systematic search was conducted using PubMed, EMBASE, International Pharmaceutical Abstracts, and CINAHL from January 1, 2013 through January 14, 2022. Studies were included if they met the following criteria: pharmacy-led intervention, 30-day readmission outcomes, patients at least 18 years old, original research performed in the United States, and English language only articles. Descriptive statistics were used to summarize study characteristics, outcomes, and elements of the study interventions. RESULTS: A total of 1964 abstracts were screened with 123 studies being included in the review. A total of 110 (89.4%) studies showed a decrease in readmission rates. The largest decrease in readmission rates was 44.5% (range 0.2%-44.5%, median = 7.4%) and the most common pharmacy-led intervention was patient counseling (n = 119, 96.7%) followed by medication reconciliation (n = 111, 90.2%). High-risk patient populations were commonly targeted with 52 studies (42.3%) focusing on CMS HRRP related diagnoses. CONCLUSION: Most pharmacist-led TOC interventions contributed to lower rates of 30-day readmission. Future studies should investigate the types of interventions that most significantly impact readmission rates.

Predictors of HIV Among 1 Million Clients in High-Risk Male Populations in Tanzania.

The World Health Organization identified men as an essential group to target with HIV testing and treatment strategies;: men who have sex with men (MSM) and male clients of female sex workers (CFSW) account for 35% of new HIV infections globally. Using a cross-sectional design from a community-based HIV prevention project in Tanzania (October 2015-September 2018) and multivariable logistic regression, we identified predictors of HIV seropositivity among men. Of 1,041,343 men on their initial visit to the project, 36,905 (3.5%) were MSM; 567,005 (54.5%) were CFSW; and 437,343 (42.0%) were other men living near hotspots (OMHA). Three predictors of HIV seropositivity emerged across all three groups: being uncircumcised, having sexually transmitted infection symptoms, and harmful drinking of alcohol before sex. Any reported form of gender-based violence among MSM and OMHA and inconsistent condom use among CFSW were associated with HIV seropositivity. These findings may inform community HIV strategies like self-testing, delivery of pre-exposure prophylaxis and antiretroviral therapy, and behavioral change communication targeting men at higher risk of infection.

Public Health Implications of Adapting HIV Pre-exposure Prophylaxis Programs for Virtual Service Delivery in the Context of the COVID-19 Pandemic: Systematic Review.

BACKGROUND: The novel coronavirus disease COVID-19 caused by SARS-CoV-2 threatens to disrupt global progress toward HIV epidemic control. Opportunities exist to leverage ongoing public health responses to mitigate the impacts of COVID-19 on HIV services, and novel approaches to care provision might help address both epidemics. OBJECTIVE: As the COVID-19 pandemic continues, novel approaches to maintain comprehensive HIV prevention service delivery are needed. The aim of this study was to summarize the related literature to highlight adaptations that could address potential COVID-19-related service interruptions. METHODS: We performed a systematic review and searched six databases, OVID/Medline, Scopus, Cochrane Library, CINAHL, PsycINFO, and Embase, for studies published between January 1, 2010, and October 26, 2021, related to recent technology-based interventions for virtual service delivery. Search terms included "telemedicine," "telehealth," "mobile health," "eHealth," "mHealth," "telecommunication," "social media," "mobile device," and "internet," among others. Of the 6685 abstracts identified, 1259 focused on HIV virtual service delivery, 120 of which were relevant for HIV prevention efforts; 48 pertained to pre-exposure prophylaxis (PrEP) and 19 of these focused on evaluations of interventions for the virtual service delivery of PrEP. Of the 16 systematic reviews identified, three were specific to PrEP. All 35 papers were reviewed for outcomes of efficacy, feasibility, and/or acceptability. Limitations included heterogeneity of the studies' methodological approaches and outcomes; thus, a meta-analysis was not performed. We considered the evidence-based interventions found in our review and developed a virtual service delivery model for HIV prevention interventions. We also considered how this platform could be leveraged for COVID-19 prevention and care. RESULTS: We summarize 19 studies of virtual service delivery of PrEP and 16 relevant reviews. Examples of technology-based interventions that were effective, feasible, and/or acceptable for PrEP service delivery include: use of SMS, internet, and smartphone apps such as iText (50% [95% CI 16%-71%] reduction in discontinuation of PrEP) and PrEPmate (OR 2.62, 95% CI 1.24-5.5.4); telehealth and eHealth platforms for virtual visits such as PrEPTECH and IowaTelePrEP; and platforms for training of health care workers such as Extension for Community Healthcare Outcomes (ECHO). We suggest a virtual service delivery model for PrEP that can be leveraged for COVID-19 using the internet and social media for demand creation, community-based self-testing, telehealth platforms for risk assessment and follow-up, applications for support groups and adherence/appointment reminders, and applications for monitoring. CONCLUSIONS: Innovations in the virtual service provision of PrEP occurred before COVID-19 but have new relevance during the COVID-19 pandemic. The innovations we describe might strengthen HIV prevention service delivery during the COVID-19 pandemic and in the long run by engaging traditionally hard-to-reach populations, reducing stigma, and creating a more accessible health care platform. These virtual service delivery platforms can mitigate the impacts of the COVID-19 pandemic on HIV services, which can be leveraged to facilitate COVID-19 pandemic control now and for future responses.

Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species.

The CCR5-specific antibody Leronlimab is being investigated as a novel immunotherapy that can suppress HIV replication with minimal side effects. Here we studied the virological and immunological consequences of Leronlimab in chronically CCR5-tropic HIV-1 infected humans (n = 5) on suppressive antiretroviral therapy (ART) and in ART-naïve acutely CCR5-tropic SHIV infected rhesus macaques (n = 4). All five human participants transitioned from daily combination ART to self-administered weekly subcutaneous (SC) injections of 350 mg or 700 mg Leronlimab and to date all participants have sustained virologic suppression for over seven years. In all participants, Leronlimab fully occupied CCR5 receptors on peripheral blood CD4+ T cells and monocytes. In ART-naïve rhesus macaques acutely infected with CCR5-tropic SHIV, weekly SC injections of 50 mg/kg Leronlimab fully suppressed plasma viremia in half of the macaques. CCR5 receptor occupancy by Leronlimab occurred concomitant with rebound of CD4+ CCR5+ T-cells in peripheral blood, and full CCR5 receptor occupancy was found in multiple anatomical compartments. Our results demonstrate that weekly, self-administered Leronlimab was safe, well-tolerated, and efficacious for long-term virologic suppression and should be included in the arsenal of safe, easily administered, longer-acting antiretroviral treatments for people living with HIV-1. Trial Registration: ClinicalTrials.gov Identifiers: NCT02175680 and NCT02355184.