A Phase 1 Clinical Trial to Assess the Safety and Pharmacokinetics of a Tenofovir Alafenamide/Elvitegravir Insert Administered Rectally for HIV Prevention.

BACKGROUND: On-demand topical products could be an important tool for HIV prevention. We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide/elvitegravir (TAF/EVG; 16 mg/20 mg) insert administered rectally. METHODS: MTN-039 was a Phase 1, open-label, single-arm, 2-dose study. Blood, rectal fluid (RF), and rectal tissue (RT) were collected over 72 hours (hr) following rectal administration of one and two TAF/EVG inserts for each participant. ClinicalTrials.gov Identifier: NCT04047420. RESULTS: TAF/EVG inserts were safe and well tolerated. EVG and tenofovir (TFV) were detected in blood plasma at low concentrations: median peak concentrations after 2 inserts were EVG 2.4 ng/mL and TFV 4.4 ng/mL. RT EVG peaked at 2-hr (median 2 inserts= 9 ng/mg) but declined to BLQ in the majority of samples at 24-hr, whereas TFV-DP remained high >2,000 fmol/million cells for 72-hr with 2 inserts. Compared to baseline, median cumulative log10 HIV p24 antigen of ex vivo rectal tissue HIV infection was reduced at each timepoint for both 1 and 2 inserts (p<0.065 and p<0.039, respectively). DISCUSSION: Rectal administration of TAF/EVG inserts achieved high rectal tissue concentrations of EVG and TFV-DP with low systemic drug exposure and demonstrable ex vivo inhibition of HIV infection for 72 hours.

History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products.

The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.

RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.

Trust in federal COVID-19 vaccine oversight and parents' willingness to vaccinate their children against COVID-19: a cross-sectional study.

BACKGROUND: Over half of the youth population in the United States, aged 6 months to 17 years, have not received the Coronavirus Disease 2019 (COVID-19) vaccine. Given parents' central role in vaccinating their children, we examined associations between parents' trust of the federal oversight of COVID-19 vaccine safety and their willingness to vaccinate their children against COVID-19. METHODS: This cross-sectional study included 975 parents of minor children residing in Philadelphia who completed the online survey between September 2021 and February 2022. Trust was measured using a four-point Likert scale ranging from 'do not trust' to 'fully trust' for two variables: (1) trust in federal oversight of COVID-19 vaccine safety for children and (2) trust in federal oversight of COVID-19 vaccine safety for the general public. A multiple logistic regression evaluated associations between trust and parents' willingness to vaccinate their children, which was measured on a five-point Likert scale ranging from 'strongly disagree' to 'strongly agree.' The analysis was adjusted for race/ethnicity, age, sexual orientation, gender, education, insurance, and parents' vaccination status. RESULTS: Analyses included 975 parents whose children had not previously been vaccinated against COVID-19 (mean age 36.79, standard deviation 6.4; 42.1% racial/ethnic minorities; 93.2% heterosexual; and 73.7% with a college degree). Greater trust regarding federal oversight of COVID-19 vaccine safety for children [adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.13-2.04] and for the public (aOR = 1.58, 95% CI: 1.17-2.14) were each associated with increased willingness to have their child vaccinated against COVID-19. Unvaccinated parents had decreased willingness compared to parents who had received at least one dose of the vaccine (aOR = 0.14, 95% CI: 0.04-0.41). College-graduate parents exhibited increased willingness compared to those without a college degree (aOR = 2.07, 95% CI: 1.52-2.81). Non-heterosexual parents showed increased willingness compared to heterosexual parents (aOR = 2.30, 95% CI: 1.20-4.76). CONCLUSIONS: Trust in federal COVID-19 vaccine oversight was associated with parental willingness to vaccinate their children against COVID-19 among parents whose children have not yet been vaccinated. Identifying and addressing causes of mistrust are crucial next steps to promote child vaccination. Intervention efforts to address trust gaps should remain a public health priority.

Direct and Indirect Effects of Cannabis Risk Perceptions on Cannabis Use Frequency.

Background: Perceived risk of harm associated with cannabis use has decreased in recent decades, particularly among emerging adults who show the highest prevalence of use. Cannabis-related protective behavioral strategies (PBS) are associated with lower cannabis use and fewer consequences; however, individuals who perceive using cannabis as low risk may use cannabis PBS less often. Therefore, using cross-sectional data, we examined the associations between perceived risk of harm associated with cannabis use, cannabis PBS, and cannabis use frequency. Method: Participants were 146 emerging adults between the ages of 18-25 (56.2% female) who reported consuming cannabis at least 3 times/week and completed measures of past-month cannabis use, past three-month use of cannabis PBS, and perceived risk of harm associated with cannabis use. Path analyses examined direct and indirect effects of perceived risk of cannabis-related harm on cannabis frequency through cannabis PBS. Results: Most (66.4%) participants reported no perceived risk of harm associated with occasional cannabis use, whereas 30.1% reported no perceived risk of harm associated with regular cannabis use. Findings indicated a significant indirect effect between perceived risk of harm and cannabis use frequency through cannabis PBS, b = -10.23, SE = 3.80, 95% CI [-17.67, -2.80], p = .007. Conclusions: Among emerging adults who consume cannabis regularly, findings suggest that a greater perceived risk of cannabis-related harm is associated with decreased cannabis use frequency via increased use of cannabis PBS. Although future analyses evaluating causal mechanisms are needed, these findings have clinical implications for harm reduction interventions focused on cannabis use.

Determining the Innovativeness of Nurses Who Engage in Activities That Encourage Innovative Behaviors.

BACKGROUND: We sought to understand the innovativeness of nurses engaging in innovative behaviors and quantify the associated characteristics that make nurses more able to innovate in practice. We first compared the innovativeness scores of our population; then we examined those who self-identified as an innovator versus those who did not to explore differences associated with innovativeness between these groups. METHODS: A cross-sectional survey study of nurses in the US engaging in innovative behaviors was performed. We performed an exploratory factor analysis (EFA) to determine the correlates of innovative behavior. RESULTS: Three-hundred and twenty-nine respondents completed the survey. Respondents who viewed themselves as innovators had greater exposure to HCD/DT workshops in the past year (55.8% vs. 36.6%, p = 0.02). The mean innovativeness score of our sample was 120.3 ± 11.2 out of a score of 140. The mean innovativeness score was higher for those who self-identified as an innovator compared with those who did not (121.3 ± 10.2 vs. 112.9 ± 14.8, p =< 0.001). The EFA created four factor groups: Factor 1 (risk aversion), Factor 2 (willingness to try new things), Factor 3 (creativity and originality) and Factor 4 (being challenged). CONCLUSION: Nurses who view themselves as innovators have higher innovativeness scores compared with those who do not. Multiple individual and organizational characteristics are associated with the innovativeness of nurses.

HIV pre-exposure prophylaxis programme preferences among sexually active HIV-negative transgender and gender diverse adults in the United States: a conjoint analysis.

INTRODUCTION: Current implementation efforts have failed to achieve equitable HIV pre-exposure prophylaxis (PrEP) provision for transgender and gender-diverse (trans) populations. We conducted a choice-based conjoint analysis to measure preferences for key attributes of hypothetical PrEP delivery programmes among a diverse online sample predominantly comprised of transmasculine and nonbinary individuals in the United States. METHODS: Between April 2022 and June 2022, a national online survey with an embedded conjoint analysis experiment was conducted among 304 trans individuals aged ≥18 years in the United States to assess five PrEP programme attributes: out-of-pocket cost; dispensing venue; frequency of visits for PrEP-related care; travel time to PrEP provider; and ability to bundle PrEP-related care with gender-affirming hormone therapy services. Participants responded to five questions, each of which presented two PrEP programme scenarios and one opt-out option per question and selected their preferred programme in each question. We used hierarchical Bayes estimation and multinomial logistic regression to measure part-worth utility scores for the total sample and by respondents' PrEP status. RESULTS: The median age was 24 years (range 18-56); 75% were assigned female sex at birth; 54% identified as transmasculine; 32% as nonbinary; 14% as transfeminine. Out-of-pocket cost had the highest attribute importance score (44.3%), followed by the ability to bundle with gender-affirming hormone therapy services (18.7%). Minimal cost-sharing ($0 out-of-pocket cost) most positively influenced the attribute importance of cost (average conjoint part-worth utility coefficient of 2.5 [95% CI 2.4-2.6]). PrEP-experienced respondents preferred PrEP delivery in primary care settings (relative utility score 4.7); however, PrEP-naïve respondents preferred pharmacies (relative utility score 5.1). CONCLUSIONS: Participants preferred programmes that offered PrEP services without cost-sharing and bundled with gender-affirming hormone therapy services. Bolstering federal regulations to cover PrEP services and prioritizing programmes to expand low-barrier PrEP provision are critical to achieving equitable PrEP provision. Community-engaged implementation research conducted by and in close collaboration with trans community stakeholders and researchers are needed to streamline the design of patient-centred PrEP programmes and develop implementation strategies that are salient to the diverse sexual health needs of trans patients.

Psychosocial correlates of parents' willingness to vaccinate their children against COVID-19.

BACKGROUND: Public health guidance recommended that children who are 6 months or older be vaccinated against COVID-19 in June of 2022. In the U.S., 56% of children under 17 had not received the COVID-19 vaccination in 2023. We examine parents' willingness to vaccinate their children against COVID-19 using the theory of planned behavior in order to design effective strategies to promote vaccine uptake. METHODS: The Philadelphia Community Engagement Alliance is part of an NIH community-engaged consortium focused on addressing COVID-19 disparities across the U.S. We surveyed 1,008 Philadelphia parents (mean age 36.86, SD 6.55; 42.3% racial/ethnic minorities) between September 2021 and February 2022, a period when guidance for child vaccination was anticipated. Structural Equation Modeling analysis examined associations between parental willingness and vaccine-related attitudes, norms, and perceived control. Covariates included parents' COVID-19 vaccination status, race/ethnicity, gender, and survey completion post-CDC pediatric COVID-19 vaccination guidelines. Subgroup analyses by race/ethnicity and gender were conducted. RESULTS: Our model demonstrated good fit (χ2 = 907.37, df = 419, p<0.001; comparative fit index [CFI] = 0.951; non-normed fit index [NNFI] = 0.946; root mean square error of approximation [RMSEA] = 0.034 with 95% CI = 0.030-0.038). Attitudes ([Formula: see text] = 0.447, p<0.001) and subjective norms ([Formula: see text] = 0.309, p = 0.002) were predictors of intention. Racial/ethnic minority parents exhibited weaker vaccination intentions ([Formula: see text] = -0.053, p = 0.028) than non-Hispanic White parents. CONCLUSIONS: Parents' attitudes and norms influence their vaccination intentions. Despite the survey predating widespread child vaccine availability, findings are pertinent given the need to increase and sustain pediatric vaccinations against COVID-19. Interventions promoting positive vaccine attitudes and prosocial norms are warranted. Tailored interventions and diverse communication strategies for parental subgroups may be useful to ensure comprehensive and effective vaccination initiatives.

Health activism, vaccine, and mpox discourse: BERTopic based mixed-method analyses of tweets from sexual minority men and gender diverse (SMMGD) individuals in the U.S.

Objectives: To synthesize discussions among sexual minority men and gender diverse (SMMGD) individuals on mpox, given limited representation of SMMGD voices in existing mpox literature. Methods: BERTopic (a topic modeling technique) was employed with human validations to analyze mpox-related tweets (n = 8,688; October 2020-September 2022) from 2,326 self-identified SMMGD individuals in the U.S.; followed by content analysis and geographic analysis. Results: BERTopic identified 11 topics: health activism (29.81%); mpox vaccination (25.81%) and adverse events (0.98%); sarcasm, jokes, emotional expressions (14.04%); COVID-19 and mpox (7.32%); government/public health response (6.12%); mpox symptoms (2.74%); case reports (2.21%); puns on the virus' naming (i.e., monkeypox; 0.86%); media publicity (0.68%); mpox in children (0.67%). Mpox health activism negatively correlated with LGB social climate index at U.S. state level, ρ = -0.322, p = 0.031. Conclusions: SMMGD discussions on mpox encompassed utilitarian (e.g., vaccine access, case reports, mpox symptoms) and emotionally-charged themes-advocating against homophobia, misinformation, and stigma. Mpox health activism was more prevalent in states with lower LGB social acceptance. Public Health Implications: Findings illuminate SMMGD engagement with mpox discourse, underscoring the need for more inclusive health communication strategies in infectious disease outbreaks to control associated stigma.

Mpox Discourse on Twitter by Sexual Minority Men and Gender-Diverse Individuals: Infodemiological Study Using BERTopic.

BACKGROUND: The mpox outbreak resulted in 32,063 cases and 58 deaths in the United States and 95,912 cases worldwide from May 2022 to March 2024 according to the US Centers for Disease Control and Prevention (CDC). Like other disease outbreaks (eg, HIV) with perceived community associations, mpox can create the risk of stigma, exacerbate homophobia, and potentially hinder health care access and social equity. However, the existing literature on mpox has limited representation of the perspective of sexual minority men and gender-diverse (SMMGD) individuals. OBJECTIVE: To fill this gap, this study aimed to synthesize themes of discussions among SMMGD individuals and listen to SMMGD voices for identifying problems in current public health communication surrounding mpox to improve inclusivity, equity, and justice. METHODS: We analyzed mpox-related posts (N=8688) posted between October 2020 and September 2022 by 2326 users who self-identified on Twitter/X as SMMGD and were geolocated in the United States. We applied BERTopic (a topic-modeling technique) on the tweets, validated the machine-generated topics through human labeling and annotations, and conducted content analysis of the tweets in each topic. Geographic analysis was performed on the size of the most prominent topic across US states in relation to the University of California, Los Angeles (UCLA) lesbian, gay, and bisexual (LGB) social climate index. RESULTS: BERTopic identified 11 topics, which annotators labeled as mpox health activism (n=2590, 29.81%), mpox vaccination (n=2242, 25.81%), and adverse events (n=85, 0.98%); sarcasm, jokes, and emotional expressions (n=1220, 14.04%); COVID-19 and mpox (n=636, 7.32%); government or public health response (n=532, 6.12%); mpox symptoms (n=238, 2.74%); case reports (n=192, 2.21%); puns on the naming of the virus (ie, mpox; n=75, 0.86%); media publicity (n=59, 0.68%); and mpox in children (n=58, 0.67%). Spearman rank correlation indicated significant negative correlation (ρ=-0.322, P=.03) between the topic size of health activism and the UCLA LGB social climate index at the US state level. CONCLUSIONS: Discussions among SMMGD individuals on mpox encompass both utilitarian (eg, vaccine access, case reports, and mpox symptoms) and emotionally charged (ie, promoting awareness, advocating against homophobia, misinformation/disinformation, and health stigma) themes. Mpox health activism is more prevalent in US states with lower LGB social acceptance, suggesting a resilient communicative pattern among SMMGD individuals in the face of public health oppression. Our method for social listening could facilitate future public health efforts, providing a cost-effective way to capture the perspective of impacted populations. This study illuminates SMMGD engagement with the mpox discourse, underscoring the need for more inclusive public health programming. Findings also highlight the social impact of mpox: health stigma. Our findings could inform interventions to optimize the delivery of informational and tangible health resources leveraging computational mixed-method analyses (eg, BERTopic) and big data.

Engaging Trusted Messengers to Increase COVID-19 Pediatric Vaccine Uptake in Philadelphia: Lessons from the VaxUpPhillyFamilies program.

INTRODUCTION: Communities of color had higher rates of Coronavirus (COVID-19) infection and lower rates of COVID-19 vaccination during the pandemic. Parental concern about the safety and necessity of pediatric COVID-19 vaccines contribute to low childhood vaccination. Enlisting parents and caregivers as trusted messengers is an evidence-based approach to mitigate this challenge. VaxUpPhillyFamilies was formed to engage parents and caregivers as vaccine ambassadors to increase vaccination rates in children of color. This study aimed to understand the key benefits, challenges, and lessons learned from the VaxUpPhillyFamilies program. METHODS: Three online debriefing sessions with ambassadors were conducted between September 7 and October 24, 2022, to share best practices, address challenges, receive emerging vaccine information, and provide support. Thematic analysis was utilized to develop broad themes and subthemes. RESULTS: Four themes with corresponding subthemes were identified: 1) Motivations to Become an Ambassador: a) improving the health of the community and b) personal satisfaction; 2) Defining Success: a) community interactions and b) influencing opinions; 3) Best Approaches: a) being mentally prepared with facts, b) addressing community health needs beyond COVID-19, c) demonstrating empathy, d) "meeting them where they're at" by motivational interviewing, and e) building trust and connection; 4) Challenges: a) changes in vaccine guidelines, b) vaccine misinformation, c) varied perceptions of severity of COVID-19 illness and benefits of the vaccine, d) breakdown of communication from trusted sources, and e) structural barriers to engagement. CONCLUSION: Parents and caregivers were a resource for delivering evidence-based messaging about COVID-19 and other health challenges. To effectively equip parents and caregivers as public health ambassadors, it is critical to offer training in engagement strategies, to identify and combat misinformation, and to provide support in navigating challenges. VaxUpPhillyFamilies program is a model for future public health campaigns.

Efficacy of a Digital Health Preventive Intervention for Adolescents With HIV or Sexually Transmitted Infections and Substance Use Disorder: Protocol for a Randomized Controlled Trial.

BACKGROUND: HIV or sexually transmitted infections remain a significant public health concern in the United States, with adolescents affected disproportionately. Adolescents engage in HIV/STI risk behaviors, including drug use and condomless sex, which increase the risk for HIV/STIs. At-risk adolescents, many of whom are racial minorities, experience HIV/STI disparities. Although at-risk adolescents are disproportionately affected by HIV/STI risk behaviors and infections and although the Centers for Disease Control and Prevention recommends routine HIV/STI testing for adolescents, relatively few adolescents report having ever been tested for HIV/STI. With expected increases in health clinic visits as a result of the Affordable Care Act combined with technological advances, health clinics and mobile health (mHealth), including apps, provide innovative contexts and tools to engage at-risk adolescents in HIV/STI prevention programs. Yet, there is a dearth of efficacious mHealth interventions in health clinics to prevent and reduce both condomless sex and drug use and increase HIV/STI testing for at-risk adolescents. OBJECTIVE: To address this gap in knowledge, we developed a theory-driven, culturally congruent mHealth intervention (hereon referred to as S4E [Storytelling 4 Empowerment]) that has demonstrated feasibility and acceptability in a clinical setting. The next step is to examine the preliminary efficacy of S4E on adolescent HIV/STI testing and risk behaviors. This goal will be accomplished by 2 aims: the first aim is to develop a cross-platform and universal version of S4E. The cross-platform and universal version of S4E will be compatible with both iOS and Android operating systems and multiple mobile devices, aimed at providing adolescents with ongoing access to the intervention once they leave the clinic, and the second aim is to evaluate the preliminary efficacy of S4E, relative to usual care control condition, in preventing or reducing drug use and condomless sex and increasing HIV/STI testing in a clinical sample of at-risk adolescents aged 14-21 years living in Southeast Michigan. METHODS: In this study, 100 adolescents recruited from a youth-centered community health clinic will be randomized via blocked randomization with random sequences of block sizes to one of the 2 conditions: S4E mHealth intervention or usual care. Theory-driven and culturally congruent, S4E is an mHealth adaptation of face-to-face storytelling for empowerment, which is registered with the Substance Abuse and Mental Health Services Administration's National Registry of Evidence-Based Programs and Practices. RESULTS: This paper describes the protocol of our study. The recruitment began on May 1, 2018. This study was registered on December 11, 2017, in ClinicalTrials.gov. All participants have been recruited. Data analysis will be complete by the end of March 2024, with study findings available by December 2024. CONCLUSIONS: This study has the potential to improve public health by preventing HIV/STI and substance use disorders. TRIAL REGISTRATION: ClinicalTrials.gov NCT03368456; https://clinicaltrials.gov/study/NCT03368456. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47216.