Search Results (43)

Background/Objectives: Multipurpose prevention technologies (MPTs) that combine protection against HIV and unintended pregnancy can improve women’s health outcomes by simplifying use and enhancing adherence. We developed a long-acting (LA) implant for the simultaneous and sustained delivery of the antiretroviral islatravir (ISL) and the contraceptive hormone etonogestrel (ENG). Methods: Using extruded poly-ε-caprolactone (PCL) tubing, reservoir-style implants were fabricated and evaluated in three configurations: (Group 1) a two-segment implant formed by joining separate ISL- and ENG-containing tubes; (Group 2) a single tube divided into two drug compartments by a heat-sealed PCL spacer; (Group 3) separate single-drug implants. In vitro release was assessed in phosphate-buffered saline at 37 °C, and safety and pharmacokinetic (PK) profiles were evaluated in New Zealand White rabbits (n = 4/group) over approximately 90 days. Results: The average ISL daily in vitro release rates for Groups 1, 2, and 3 were 29 ± 5 µg/day, 18 ± 5 µg/day, and 47 ± 8 µg/day, respectively, and ENG daily in vitro release rates were 39 ± 9 µg/day, 41 ± 8 µg/day, and 33 ± 7 µg/day. From day 28 through the end of the study, median (IQR) plasma concentrations were 0.22 (0.18–0.27) ng/mL, 0.28 (0.24–0.33) ng/mL, and 0.31 (0.28–0.33) ng/mL for ISL in Groups 1, 2, and 3, respectively, and 0.26 (0.21–0.31) ng/mL, 0.25 (0.16–0.47) ng/mL, and 0.30 (0.23–0.38) ng/mL for ENG in Groups 1, 2 and 3, respectively. Implants across all groups were well tolerated and demonstrated favorable local tolerability over the 90-day dosing period. Conclusions: Integration of multiple indications into a single platform capable of sustained release over an extended duration holds potential to address persistent gaps in women’s sexual and reproductive health needs. Full article

Historically, TEM prep has been an artisan craft without a systematic workflow that ensures quantified control over TEM sample thickness. Over- and under-thinning is a significant problem in the TEM prep process. A direct measurement process was demonstrated to control the final thickness of the TEM lamella. Final lamella thickness was controlled by directly measuring lamella thickness in real time using a 10–15 kV SEM while performing secondary electron imaging at the mill position, allowing for (human-mediated) closed-loop processing. We demonstrated the utility of this technique by systematically thinning five TEM samples to discretely target thicknesses ranging from 100 nm down to 28 nm. We demonstrated the repeatability and simplicity of the process by fabricating 10 STEM lamella with a targeted thickness of 32 nm. We demonstrate the ability to fabricate an engineered multi-layered structure that acts as a lamella thickness measurement feature that is independent of sample type, allowing a broader implementation of in-line lamella thickness monitoring. We applied our thickness measurement technique to three thin-film materials (Au, Ag, and Cu) to obtain TEM lamella thickness target values needed to achieve electron transparency for each material. Having knowledge of a target thickness parameter prevents the over- and under-thinning problem in TEM prep. Full article

Influenza remains a significant national health security threat, particularly for vulnerable populations, as existing control measures do not fully mitigate its impact. This gap in protection is especially pronounced early in a pandemic when a well-matched vaccine may not yet be available, as well as in populations unable to mount an optimal vaccine response. Clinical studies support pre-exposure prophylaxis (PrEP) therapeutics as a promising complementary strategy to reduce influenza transmission and disease severity, potentially easing the strain on healthcare systems during outbreaks. This manuscript outlines the Biomedical Advanced Research and Development Authority’s (BARDA’s) target product profile (TPP) for a long-acting influenza PrEP product, reviews the current development landscape, and models the potential impact of early PrEP product deployment using agent-based modeling in a synthetic population of 19.5 million people across pandemic scenarios resembling the 1918, 1968, and 2009 influenza pandemics. Simulations showed that early deployment of a 70%–effective PrEP reduced cumulative and peak infections, delayed the epidemic peak, and provided the greatest benefit in less transmissible pandemics; at 40–50% coverage, PrEP fully mitigated a 2009-like pandemic and substantially reduced transmission in 1918- and 1968-like scenarios. The TPP defines key characteristics of an effective PrEP option for seasonal and pandemic influenza that (1) demonstrates a strong safety and tolerability profile across all populations; (2) targets a direct-acting antiviral mechanism of action; (3) reduces the relative risk of symptomatic influenza infection by at least 70% in an unvaccinated population and (4) provides single-dose, season-long protection to optimize patient adherence. In this context, integrating PrEP into influenza prevention strategies could improve control of virus spread, strengthen protection for high-risk groups, and significantly reduce the overall public health impact of seasonal and pandemic influenza. Full article

Background: The development of an efficacious preventive human immunodeficiency virus (HIV) vaccine remains a central goal of global HIV elimination efforts, yet biological performance alone will not determine a future vaccine’s public health impact. Method: This review draws on behavioral science, communication research, vaccine implementation, and HIV prevention literature to identify cognitive, social, and structural challenges that are likely to shape public acceptance and uptake of a future HIV vaccine, as well as to outline evidence-based opportunities for addressing them. Results: Based on the available literature, mental models of both HIV and vaccination will be a critical determinant of how communities consider a future vaccine, particularly given that emerging mRNA and adjuvanted platforms may generate side effects that could be easily misinterpreted and that highly effective long-acting pre-exposure prophylaxis (PrEP) options already exist and will shape how individuals evaluate a vaccine’s relative value. HIV-related stigma further complicates this landscape by making vaccination a socially interpreted behavior, unlike some other vaccination efforts. Together, these factors suggest that hesitancy and misalignment between public understanding and scientific evidence are predictable and should be anticipated rather than addressed reactively. At the same time, decades of HIV prevention implementation research have established an evidence base for vaccine communication, and existing community engagement infrastructure offers a foundation upon which future rollout efforts can build. We highlight three evidence-based strategies as particularly promising levers for encouraging acceptance and adoption. Conclusions: We conclude with recommendations for HIV vaccine researchers and healthcare professionals to invest in formative research, build community partnerships in advance of vaccine availability, and pilot integrated delivery models within existing HIV prevention services. Full article

The coronavirus (COVID-19) pandemic necessitated unprecedented regulatory responses that enabled rapid therapeutic deployment. The integrated medico-legal framework—comprising the FD&C Act Section 564 (Emergency Use Authorization/EUA), PREP Act (liability immunity), and CICP (injury compensation)—facilitated emergency response while protecting all stakeholders. This normative legal and policy analysis examines nirmatrelvir/ritonavir (Paxlovid) as a case study, integrating emerging pharmacokinetic evidence demonstrating its passage across the blood–brain and blood–placenta barriers. The EUA-PREP-CICP framework achieved notable results: nirmatrelvir/ritonavir’s authorization enabled deployment approximately 1 year after trials began, demonstrating an 89% reduction in the risk of hospitalization or death and potentially preventing thousands of hospitalizations. The PREP Act enabled focused pharmaceutical development and protected frontline healthcare workers during the crisis, though access barriers and transparency concerns remain areas warranting ongoing attention. The CICP provided administrative compensation for qualifying injuries, with acknowledged limitations in filing timelines and causation standards. Pharmacokinetic studies published after authorization revealed biological barrier crossing, representing normal scientific progress through continued investigation. The EUA-PREP-CICP nexus functioned as an integrated system: EUA enabled rapid evidence-based access, PREP immunity facilitated development and deployment, and CICP provided injury remedy. Based on this experience, this study proposes targeted enhancements to further strengthen this framework: systematic post-authorization surveillance timelines, enhanced special population monitoring through registries, modest procedural refinements to CICP, and improved surveillance infrastructure. These evidence-based improvements would build on the framework’s demonstrated strengths, optimizing performance for future emergencies while preserving the essential functions that helped address the COVID-19 pandemic. Full article

Background/Objectives: Women and girls, particularly in sub-Saharan Africa, face high risks for both HIV and unintended pregnancy. Inconsistent condom use underscores the need for new multipurpose prevention technologies (MPTs) that combine HIV pre-exposure prophylaxis (PrEP) and contraception. Long-acting (LA) injectables are especially promising. To this end, an LA cabotegravir (CAB)/medroxyprogesterone acetate (MPA) in situ-forming implant (ISFI) has been developed. We report pharmacokinetic (PK) modeling to characterize CAB and MPA disposition and absorption to support the development of the MPT ISFI. Methods: Female BALB/c mice received single intravenous (IV) or subcutaneous (SQ) bolus doses of CAB or MPA. Sparse plasma samples were collected (~3 mice/timepoint) for PK analysis by LC-MS/MS. Noncompartmental analysis assessed SQ bioavailability. Macroparameterized compartmental PK models were fit to IV data to derive unit impulse responses (UIRs) for each drug. Results: CAB and MPA exhibited 61% and 42% bioavailability, respectively. CAB IV PK was best described by a two-compartment model with macroconstant parameters: A = 16,621 ng/mL, α = 4.52 h⁻¹, B = 30,206 ng/mL, and β = 0.053 h⁻¹. MPA IV PK was also best described by a two-compartment model, with A = 2506 ng/mL, α = 10.5 h⁻¹, B = 439 ng/mL, and β = 0.65 h⁻¹. These values define the UIR for CAB and MPA. Conclusions: Our IV PK modeling framework fully characterizes CAB/MPA disposition in mouse, enabling downstream deconvolution-based estimation of absorption from controlled-release formulations. This provides a foundation for in vitro–in vivo correlation, facilitating preclinical evaluation of long-acting formulations such as ISFIs. Full article

Long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) demonstrates superior efficacy and persistence compared to daily oral PrEP. However, real-world implementation reveals that only 52.9% of prescribed individuals initiate treatment with their first injection. This implementation barrier stems from a fundamental mismatch between the traditional PrEP cascade—designed for oral formulations allowing same-day initiation—and LAI-PrEP’s unique requirements involving a 2–8 week “bridge period” between prescription and first injection to establish HIV-negative status. We synthesize data from major clinical trials (HPTN 083, HPTN 084, PURPOSE-1/2; >15,000 participants) with real-world implementation studies to characterize bridge period navigation as the critical implementation barrier. This review proposes a reconceptualized PrEP cascade explicitly recognizing the bridge period as a distinct, measurable step requiring dedicated management strategies. We examine pharmacological bases for conservative initiation protocols, quantify population-specific barriers to bridge period completion, and synthesize evidence on strategies to improve initiation success. This paradigm shift from individual behavioral adherence to structural factors within the healthcare system requires parallel innovations in cascade conceptualization, measurement frameworks, and implementation approaches. Addressing this structural barrier is essential to translate LAI-PrEP’s extraordinary clinical efficacy (>96%) into meaningful public health impact, particularly for populations experiencing the highest HIV burden. Full article

Long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) demonstrates superior efficacy to oral PrEP but faces a critical implementation challenge: 47% of patients fail to receive their first injection during the “bridge period” between prescription and initiation. We developed a clinical decision support tool with an external configuration architecture synthesizing evidence from major LAI-PrEP trials (HPTN 083, HPTN 084, PURPOSE) and implementation studies. The tool provides population-specific risk stratification, barrier identification, and evidence-based intervention recommendations from a library of 21 interventions with mechanism diversity scoring to prevent redundant recommendations. We conducted progressive validation on four scales: 1000 (functional), 1,000,000 (large-scale), 10,000,000 (ultra-large-scale) and 21,200,000 patients (UNAIDS PrEP target), with comprehensive unit testing achieving a test pass rate of 100% (18/18 edge cases). Progressive validation demonstrated convergence and increasing precision: 1K (±2.6 pp), 1M (±0.09 pp), 10M (±0.028 pp), and 21.2M (±0.018 pp). At UNAIDS 2025 PrEP target (21.2 million) scale, the tool predicted baseline bridge period success rate of 23.96% (95% CI: 23.94–23.98%), with evidence-based interventions improving success to 43.50% (95% CI: 43.48–43.52%)—an absolute improvement of 19.54 pp (or 81.6% relative improvement), representing 4.1 million additional successful transitions globally. Population disparities were substantial: People who inject drugs (PWID) showed 10.36% baseline success versus 33.11% for men who have sex with men (MSM)—a 22.75 pp gap. Regional disparities were equally significant: Sub-Saharan Africa (serving 62% of global patients) achieved 21.69% baseline versus 29.33% in Europe/Central Asia—a 7.64 pp gap. However, evidence-based interventions disproportionately benefited vulnerable populations. PWID experienced +265% relative improvement, and adolescents experienced +147% relative improvement, demonstrating that systematic implementation support can narrow rather than widen health equity gaps at UNAIDS 2025 PrEP target (21.2 million) scale. The tool demonstrates predictive validity with policy-grade statistical precision. Using published epidemiologic parameters (HIV incidence 2–5% among indicated users, LAI-PrEP efficacy 96%), our model translates the 4.1 million additional successful transitions into approximately 80,000–100,000 prevented HIV infections annually (midpoint: 100,000), corresponding to an estimated USD 40 billion in averted lifetime treatment costs. Full article

Background: Daily oral preexposure prophylaxis (PrEP) is one strategy employed to decrease HIV transmission among adolescent girls and young women (AGYW). The Determined, Resilient, Empowered, AIDS-Free, Mentored, and Safe (DREAMS) program, funded by PEPFAR/USAID and implemented by the Project HOPE Namibia (PHN)-led consortium, provided services in the Khomas, Oshikoto, Zambezi, and Oshana regions. This study assessed the one-month PrEP retention rate among AGYW 15–24 and the associated factors. Methods: The program’s target populations for PrEP included AGYW aged 15–24 years who were at substantial risk for HIV, tested HIV-negative, and resided in the regions where the PHN-led consortium was implementing the DREAMS program. Data between 2018 and 2024 were exported from DHIS2 to IBM SPSS version 29 for secondary data analysis. We analyzed the data using Chi-squared tests and binomial and multinomial logistic regression. Results: Among the 17,277 participants newly initiated on oral PrEP and included in this study, only 2466 returned on time for their one-month appointment. The one-month PrEP retention rate among AGYW was 14.3%, 95% CI (13.8–14.8%). The most common reasons for PrEP discontinuation were traveling away from home, not needing PrEP anymore, forgetfulness, and side effects. Participants from Oshakati and Onandjokwe exhibited a higher likelihood of one-month PrEP retention. Additionally, participants who were in the programs for 7–12 months or over 36 months, who attended the safe space HIV prevention sessions, who were unaware of their partners’ HIV status, and who considered themselves at risk of HIV also exhibited a lower likelihood of one-month PrEP retention. In contrast, individuals who had 1–2 children and those who were either pregnant or breastfeeding exhibited a higher likelihood of one-month PrEP retention, (COR) = 1.28, 95% CI (1.15–1.43), and COR = 2.00, 95% CI (1.62–2.46), respectively. Conclusions: Targeted, innovative, and context-specific strategies should be developed to support AGYW in identifying their HIV risk and continuing the use of daily oral PrEP during periods of heightened risk. Additionally, prioritizing the introduction of discreet, long-acting PrEP options that require less frequent administration may better align with their needs and preferences. Full article

The global fight against HIV/AIDS has been significantly bolstered by the development and implementation of pre-exposure prophylaxis (PrEP), yet innovation in PrEP interventions, improved adherence and greater access are still needed to maximize its benefit. Nonhuman primate (NHP) infection with simian immunodeficiency virus (SIV) has served as an instrumental animal model in advancing HIV PrEP research. This review comprehensively examines the utility of NHP models in evaluating the efficacy, pharmacokinetics, and safety of diverse PrEP strategies, including oral, injectable, implantable, and topical formulations. It discusses the development of diverse challenge models that simulate human transmission routes and the advantages of NHPs in enabling controlled and mechanistically informative studies. It also highlights the successful translation of pivotal NHP studies evaluating tenofovir-based regimens as well the long-acting agents, cabotegravir and lenacapavir, into the clinical settings, emphasizing the consistently high predictive power of the NHP models for the HIV PrEP clinical efficacy. Finally, it underscores the importance of species-specific pharmacologic considerations and the value of NHP data in informing clinical trial design. As the global community strives to end the HIV epidemic as a public health threat in the absence of an efficacious prophylactic vaccine, NHP models make a critical contribution in the development of next-generation HIV prevention tools. Full article

Background: Pharmacy technicians are increasingly involved in immunization services, enhancing vaccine accessibility and reducing pharmacies’ workload. This scoping review aims to (1) provide a comprehensive overview of pharmacy technicians’ involvement in immunization services across various healthcare settings and countries, and (2) conduct a comparative analysis of training curricula for pharmacy technicians on immunization. Methods: A scoping review was conducted following the Arksey and O’Malley framework. A comprehensive search of the PubMed and Scopus databases was performed using keywords and MeSH terms such as “pharmacy technician(s)”, “immunization”, “vaccination”, “role”, and “involvement”. Studies included assessed pharmacy technicians’ roles in vaccine administration, training, and public health outcomes. Descriptive and thematic analyses were used to synthesize the findings. In addition, a supplementary analysis of immunization training curricula was conducted, reviewing programs from different countries to identify similarities, differences, and gaps in course structure, content, and delivery formats. Lastly, a comprehensive toolkit was developed, offering guidelines intended to facilitate the implementation of immunization training programs. Results: A total of 35 articles met the inclusion criteria, primarily from the United States of America (n = 30), Canada (n = 2), Ethiopia (n = 1), Denmark (n = 1) and United Kingdom (n = 1). The findings indicate that pharmacy technicians contribute significantly to vaccine administration, patient education, and workflow optimization, particularly in community pharmacies. The COVID-19 pandemic accelerated their involvement in immunization programs. Key challenges include regulatory barriers, a lack of standardized training, and resistance from other healthcare professionals. Facilitators include legislative support (e.g., the PREP Act), structured training programs, and collaborative pharmacist–technician models. Conclusions: Pharmacy technicians can play a vital role in expanding immunization services, improving vaccine uptake, and reducing pharmacist workload. Addressing regulatory inconsistencies, enhancing training, and fostering interprofessional collaboration are crucial for their effective integration of immunization programs. Since immunization by pharmacy technicians is not yet allowed in many EU countries, this review will provide a foundational basis to address their potential to support the healthcare workforce and improve access to immunization services. Full article

South Africa continues to experience a high HIV prevalence, necessitating innovative prevention strategies aligned with the UNAIDS 95-95-95 targets. Long-acting injectable pre-exposure prophylaxis (PrEP), such as cabotegravir (CAB-LA), offers a promising alternative to daily oral regimens. However, the perspectives of primary healthcare workers (PHCWs)—key implementers of this intervention—remain underexplored. This scoping review aims to systematically map existing literature on PHCWs’ knowledge, awareness, perceptions, barriers, facilitators, and implementation experiences related to injectable PrEP within the South African healthcare context. The review will follow the Arksey and O’Malley framework, enhanced by Levac et al., and will be reported following PRISMA-ScR guidelines. A comprehensive search will be conducted across PubMed, Scopus, CINAHL (EBSCOhost), Web of Science, and Google Scholar, without language or date restrictions. The search strategy will employ both controlled vocabulary (e.g., MeSH and CINAHL Subject Headings) and free-text terms. Studies meeting the inclusion criteria will be managed using EndNote X20 and appraised using the Mixed Methods Appraisal Tool (MMAT) 2018 version. Data will be synthesized thematically and presented narratively and in tabular form. By consolidating PHCWs’ perspectives, this review will identify implementation challenges, training needs, and systemic barriers, informing the development of context-specific strategies for PrEP rollout. The findings are expected to support the design of effective, culturally relevant educational interventions and guide policymakers in strengthening HIV prevention efforts in high-burden settings. Full article

Tennessee is in the southern region of the United States and has not yet fully benefitted from HIV pre-exposure prophylaxis (PrEP). Relatively little research has focused on pivotal roles of PrEP navigators. This study examined PrEP navigator perceptions of implementing long-acting injectable (LAI) PrEP in Tennessee. Semi-structured interviews with state-funded navigators were audio-recorded, transcribed, and systematically coded using a hierarchical system. Coded transcripts were aggregated, sorted, and analyzed using an iterative inductive/deductive qualitative approach. Using the Consolidated Framework for Implementation Research (CFIR), institutional, individual, and modifying factors to initiating and transitioning to LAI PrEP were identified. Most navigators initially had limited training and experience with LAI PrEP. Navigators reported systemic barriers associated with accessibility to LAI PrEP such as health insurance, pharmaceutical policies, and cost policies. While navigators noted the continued support of the state health department, strategies for circumventing individual and structural barriers are needed for universally implementing injectable PrEP. Full article

Treatment as Prevention (TasP) and Pre-Exposure Prophylaxis (PrEP) are both widely recognized as essential biomedical tools to control HIV/AIDS. TasP calls for the immediate initiation of fully subsidized and supported antiretroviral therapy (ART) following HIV diagnosis. TasP effectively prevents progression to AIDS, and premature AIDS-related deaths among people living with HIV (PLWH), and simultaneously renders HIV non-transmissible, thus preventing onward HIV transmission. In addition, PrEP has proven effective against HIV transmission among high-risk individuals who are adherent to the regimen. PrEP traditionally consists of two antiretrovirals given orally as one pill daily: originally, tenofovir-DF plus emtricitabine (TDF-FTC), and later, tenofovir-AF (TAF) plus FTC (more recently, other options have become available, including long-acting parenteral formulations; however, these are still of limited availability). Over the last two decades, the province of British Columbia has rolled out TasP among all PLWH, and starting in 2018, PrEP was added as a strategy to reach individuals most at risk of acquiring HIV to further accelerate progress in addressing HIV/AIDS as a public health threat. Our “generalized TasP + focused PrEP” program proved to be synergistic (or multiplicative) as it relates to reducing the HIV effective reproduction number (${\mathrm{R}}_{\mathrm{e}}$). TasP lowers HIV incidence by reducing the pool of individuals able to transmit HIV, which is dependent on the extent of community plasma viral load (pVL) suppression. Meanwhile, PrEP reduces the number of potential new infections among those most susceptible to acquiring HIV in the community, independent of viral load suppression among PLWH. Our results strongly support widespread implementation of the combination of “generalized TasP + focused PrEP” strategy and underscore the importance of long-term monitoring of ${\mathrm{R}}_{\mathrm{e}}$ at a programmatic level to identify opportunities for optimizing TasP and PrEP programs. This approach aligns with the United Nations goal of “Ending HIV/AIDS as a pandemic by 2030”, both in Canada and globally. Full article

Background: Currently, the Enterobacteriaceae species are responsible for a variety of serious infections and are already considered a global public health problem, especially in underdeveloped countries, where surveillance and monitoring programs are still scarce and limited. Analyses were performed on the complete genome of an extensively antibiotic-resistant strain of Enterobater hormaechei, which was isolated from a patient with non-Hodgkin’s lymphoma, who had been admitted to a hospital in the city of Manaus, Brazil. Methods: Phenotypical identification and susceptibility tests were performed in automated equipment. Total DNA extraction was performed using the PureLink genomic DNA mini-Kit. The genomic DNA library was prepared with Illumina Microbial Amplicon Prep and sequenced in the MiSeq Illumina Platform. The assembly of the whole-genome and individual analyses of specific resistance genes extracted were carried out using online tools and the Geneious Prime software. Results: The analyses identified an extensively resistant ST90 clone of E. hormaechei carrying different genes, including bla_CTX-M-15, bla_GES-2, bla_TEM-1A, bla_ACT-15, bla_OXA-1 and bla_NDM-1, [aac(3)-IIa, aac(6′)-Ian, ant(2″)-Ia], [aac(6′)-Ib-cr, (qnrB1)], dfrA25, sul1 and sul2, catB3, fosA, and qnrB, in addition to resistance to chlorhexidine, which is widely used in patient antisepsis. Conclusions: These findings highlight the need for actions to control and monitor these pathogens in the hospital environment. Full article