Search

Introduction: Long‐acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. Methods: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. Results: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7–11.3). In total, 97% of injections were administered within the ±7‐day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. Conclusion: In this large UK‐based cohort, robust approval processes and clinic protocols facilitated on‐time injections and low rates of both discontinuation and virological failure. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion We examined adverse event (AE) reports relating to cabotegravir/rilpivirine (CAB/RPV) in the US FDA Adverse Event Reporting System (FAERS), focusing on therapeutic failure (TF) and non‐therapeutic failure (NTF) outcomes.FAERS is a database of AE and medication error reports from post‐marketing surveillance. The study was granted exempt approval by the Binghamton University Institutional Review Board. We queried reports for CAB/RPV in the FAERS system from 1 January 2021 to 31 March 2024. TFs were defined as involving any of the following terms: viral load increased, virological failure, pathogen resistance, blood HIV RNA increased, treatment failure, drug ineffective, viral mutation identified, viraemia, and therapy non‐responder. The top 20 most common AEs were also identified. Means, standard deviations, and percentages were used to characterize the sample.The study cohort consisted of 2605 reports. The reported sex of the study cohort was 50% male (n = 1295), 19% female (n = 505), and 31% unspecified (n = 805), with a mean ± standard deviation (SD) age of 46.9 ± 12.4 years (n = 378). The top three most reported AEs were TFs, product dose omissions, and injection site pain, with 377 (14.5%), 354 (13.6%), and 331 (12.7%) cases, respectively. The mean ± SD weight of people with a report of TF versus NTF was 101.8 ± 33.4 kg and 87.7 ± 26.7 kg, respectively (p = 0.0175).Our findings suggest that healthcare professionals should have a heightened awareness of potential challenges with CAB/RPV administration, including TFs and dose omissions in real‐world settings. [ABSTRACT FROM AUTHOR]

Introduction: HIV treatment currently consists of daily oral antiretroviral therapy (ART). Cabotegravir + rilpivirine long-acting (CAB + RPV LA) is the first ART available in Spain administered every 2 months through intramuscular injection by a healthcare professional (HCP). The objective of this analysis was to assess potential healthcare resource use (HRU) and cost impact of implementing CAB + RPV LA vs. daily oral ART at National Health System (NHS) hospitals. Methods: Online quantitative interviews and cost analysis were performed. Infectious disease specialists (IDS), hospital pharmacists (HP) and nurses were asked about their perception of potential differences in HRU between CAB + RPV LA vs. daily oral ART, among other concepts of interest. Spanish official tariffs were applied as unit costs to the HRU estimates (€2022). Results: 120 responders (n = 40 IDS, n = 40 HP, n = 40 nurses) estimated an average number of annual visits per patient by speciality (IDS, HP, and nurse, respectively) of 3.3 vs. 3.7; 4.4 vs. 6.2; 6.1 vs. 3.9, for CAB + RPV LA vs. daily oral ART, and 3.0 vs. 3.2; 4.8 vs. 5.8; 6.9 vs. 4.9, respectively when adjusting by corresponding specialist responses. Estimation by the total sample led to an annual total cost per patient of €2,076 vs. €2,473, being €2,032 vs. €2,237 after adjusting by corresponding HCP, for CAB + RPV LA vs. daily oral ART. Conclusions: These results suggest that the implementation of CAB + RPV LA in NHS hospitals would not incur in increased HRU-related costs compared to current daily oral ARTs, being potentially neutral or even cost-saving. Why carry out this study? • Main clinical guidelines in HIV recommend the use of daily oral antiretroviral combinations. Recently, a long-acting regimen consisting of cabotegravir plus rilpivirine (CAB + RPV LA) gluteal intramuscular injections has become available in Spain for maintaining HIV-1 suppression. • Given that the long-acting regimes are administered every 2 months, it is anticipated to have a different patient pathway within the hospital compared to daily oral ART, which may lead to changes in healthcare resources and associated costs needed for HIV treatment. What was learned from the study? • The total annual cost per patient ranged from €2,032 to €2,076 for CAB + RPV LA, and from €2,237 to €2,473 for daily oral ART. • These figures suggest that the implementation of CAB + RPV LA in Spanish NHS hospitals would not translate into increased healthcare resource utilization-related costs associated to a different patient pathway compared to current daily oral ART, being potentially cost-saving. [ABSTRACT FROM AUTHOR]

Abstract Introduction HIV treatment currently consists of daily oral antiretroviral therapy (ART). Cabotegravir + rilpivirine long-acting (CAB + RPV LA) is the first ART available in Spain administered every 2 months through intramuscular injection by a healthcare professional (HCP). The objective of this analysis was to assess potential healthcare resource use (HRU) and cost impact of implementing CAB + RPV LA vs. daily oral ART at National Health System (NHS) hospitals. Methods Online quantitative interviews and cost analysis were performed. Infectious disease specialists (IDS), hospital pharmacists (HP) and nurses were asked about their perception of potential differences in HRU between CAB + RPV LA vs. daily oral ART, among other concepts of interest. Spanish official tariffs were applied as unit costs to the HRU estimates (€2022). Results 120 responders (n = 40 IDS, n = 40 HP, n = 40 nurses) estimated an average number of annual visits per patient by speciality (IDS, HP, and nurse, respectively) of 3.3 vs. 3.7; 4.4 vs. 6.2; 6.1 vs. 3.9, for CAB + RPV LA vs. daily oral ART, and 3.0 vs. 3.2; 4.8 vs. 5.8; 6.9 vs. 4.9, respectively when adjusting by corresponding specialist responses. Estimation by the total sample led to an annual total cost per patient of €2,076 vs. €2,473, being €2,032 vs. €2,237 after adjusting by corresponding HCP, for CAB + RPV LA vs. daily oral ART. Conclusions These results suggest that the implementation of CAB + RPV LA in NHS hospitals would not incur in increased HRU-related costs compared to current daily oral ARTs, being potentially neutral or even cost-saving.

Patients with schizophrenia often experience symptoms such as poor insight and disorganized thought, which limit their ability to seek and receive care consistently. In rural settings, systemic factors, including limited resources and transportation, further contribute to difficulties in health care access. Long-acting injectable antipsychotics (LAIs) can improve medication adherence and reduce hospitalizations from relapse. Opportunities exist for pharmacists to provide individualized care and improved health care access. The pilot service took place in ambulatory care clinics and home care settings. Pharmacists performed weekly reviews of patients with active orders for LAIs, coordinated care with nonadherent patients, and offered follow-up appointments in the Patient Centered Medical Home (PCMH). For patients unable to be reached, outreach pharmacists provided psychiatric assessment and LAI medication administration at home visits. There were 10 patients with LAI prescriptions in the past year selected for review. The period reviewed was 90 days before and after start of service. Pharmacist interventions resulted in 4 patients reestablished with care who were previously lost to follow-up. The percentage of days covered by LAI fills increased from an average 26% to 67% of days covered (P = .06). Total emergency room visits related to mental health episodes decreased from 11 to 2 visits (P = .03). Four patients who did not have metabolic lab monitoring in more than 1 year received lab monitoring as indicated. PCMH pharmacy services, including home visits by outreach pharmacists, may improve access and bridge care gaps for patients on LAIs by providing community-based services in addition to traditional clinic-based care.

We assessed the prevalence and factors associated with HIV-infected patients' interest in trying long-acting injectable antiretroviral treatment (LAI-ART) along with its expected benefits and concerns, and evaluated physicians' opinions about LAI-ART. This study was set within the multi-center prospective CoRIS cohort, comprising HIV-positive adults, naïve to antiretroviral treatment (ART) at study entry, recruited from 2004 onward in 48 centers in Spain. In June 2022, we conducted a 2-day cross-sectional survey among patients across 34 CoRIS centers and sent an online questionnaire to all physicians prescribing ART in 39 CoRIS centers. Of the 271 patients included, 83.3% [95% confidence interval (CI)]: 78.0 − 87.0%) expressed interest in receiving LAI-ART. This interest was higher among men (adjusted odds ratio: 2.96; 95% CI: 1.4–6.12), those aged <50 years (2.41; 1.23 − 4.73), and individuals inconvenienced by oral ART (5.03; 1.47 − 17.15), daily intake (14.65; 3.44–62.46), carrying HIV pills constantly (7.19; 2.88 − 17.96), and taking multiple medications (3.94; 1.58 − 9.85). Among the 154 physicians surveyed, 45.5% believed LAI-ART would be the preferred option for patients. Although most physicians (92.9%) thought LAI-ART could improve patients' quality of life (QoL), concerns were raised by 37.7% and 44.2% of them regarding injection site pain and visit rescheduling, respectively. Interest in LAI-ART was higher among men, those aged <50 years, and individuals finding their oral ART inconvenient. Physicians believed LAI-ART could improve QoL and overcome treatment challenges, yet concerns were raised about its potential usage difficulties. Although most patients were interested in receiving LAI-ART, only less than half of the physicians considered it their preferred option, likely owing to concerns about missed visits and injection site pain. [ABSTRACT FROM AUTHOR]

As access to long-acting injectable antiretroviral therapy (LAI ART) expands, understanding patient perceptions and experiences around LAI should inform equitable scale-up and effective implementation strategies. This study used qualitative research design relying on semi-structured interviews conducted among persons with HIV (PWH) who were either virally suppressed on oral treatment (n = 11) or had received at least one dose of injectables (n = 7). Approximately half of participants identified as male (10/18) and most identified as African American (17/18). Among participants on oral ART, many described the prospect of injectable treatment as likely convenient and discreet, relieving the stress of remembering to take daily pill. Nearly all had heard of LAI ART prior to the interview, often from television or internet commercials. Most were excited about less frequent dosing, though expressed concern about the logistics involved in coming to clinic every two months. Many expressed uncertainties regarding the relative effectiveness of LAI ART compared with oral therapy and were wary of potential pain related to injections. In contrast, all persons on LAI ART described injection-site soreness as manageable. In addition to acknowledging the convenience of every-two-month injections, some persons receiving LAI ART expressed relief by lifting the emotional stress of taking a daily-pill that reminded them of their HIV positive status. Emerging clinical trial data supports the individual and public health benefits of LAI ART, regardless of prior viral-suppression; our work adds to a growing body of literature demonstrating the potential psychological benefits associated with this novel treatment modality for PWH regardless of recent viral-suppression. [ABSTRACT FROM AUTHOR]

A ready‐to‐use (RTU) long‐acting injectable (LAI) formulation of aripiprazole monohydrate for administration once every 2 months, available in 960 mg (Ari 2MRTU 960) or 720 mg doses, has been developed for the treatment of schizophrenia or bipolar I disorder. A previously developed and validated population pharmacokinetic model for characterizing aripiprazole plasma concentrations following administration of oral aripiprazole or aripiprazole once‐monthly (AOM) intramuscular injection was expanded to include the RTU LAI formulation of aripiprazole (Ari RTU LAI). Overall, 8899 aripiprazole pharmacokinetic samples from 1191 adults from 10 clinical trials were included in the final combined analysis data set. Aripiprazole plasma concentration‐time profiles were simulated for various Ari RTU LAI initiation and maintenance scenarios in 1000 virtual patients. Diagnostic plots demonstrated that the final population pharmacokinetic model, which incorporated data for oral aripiprazole, AOM, and Ari RTU LAI, adequately described aripiprazole concentrations following Ari RTU LAI administration. Absorption of Ari RTU LAI was modeled by a parallel zero‐order and lagged first‐order process. Simulations across multiple scenarios were performed to inform dosing recommendations, including various treatment initiation regimens for a 2‐monthly formulation of Ari RTU LAI in patients with or without prior stabilization on oral aripiprazole, and for patients switching from AOM. Additional simulations accounted for missed/delayed doses, cytochrome (CYP) 2D6 metabolizer status, and concomitant use of CYP2D6 or CYP3A4 inhibitors. Overall, simulations across a variety of scenarios demonstrated an Ari RTU LAI pharmacokinetic exposure profile that was comparable to AOM, with a longer dosing interval. [ABSTRACT FROM AUTHOR]

In situ depot gel is a type of polymeric long-acting injectable (pLAI) drug delivery system; compared to microsphere technology, its preparation process is simpler and more conducive to industrialization. To ensure the chemical stability of peptide ACTY116, we avoided the use of harsh conditions such as high temperatures, high shear mixing, or homogenization; maintaining a water-free and oxygen-free environment was also critical to prevent hydrolysis and oxidation. Molecular dynamics (MDs) simulations were employed to assess the stability mechanism between ACTY116 and the pLAI system. The initial structure of ACTY116 with an alpha helix conformation was constructed using SYBYL-X, and the copolymer PLGA was generated by AMBER 16; results showed that PLGA-based in situ depot gel improved conformational stability of ACTY116 through hydrogen bonds formed between peptide ACTY116 and the components of the pLAI formulation, while PLGA (Poly(DL-lactide-co-glycolide)) also created steric hindrance and shielding effects to prevent conformational changes. As a result, the chemical and conformational stability and in vivo long-acting characteristics of ACTY116 ensure its enhanced efficacy. In summary, we successfully achieved our objective of developing a highly stable peptide-loaded long-acting injectable (LAI) in situ depot gel formulation that is stable for at least 3 months under harsh conditions (40 °C, above body temperature), elucidating the underlying stabilisation mechanism, and the high stability of the ACTY116 pLAI formulation creates favourable conditions for its in vivo pharmacological activity lasting for weeks or even months. [ABSTRACT FROM AUTHOR]

Long-acting injectable antiretroviral therapy (LAI-ART) can offer people living with HIV (PLWH) a promising alternative to daily oral therapy. This article highlights the issues, challenges and conditions related to introducing LAI-ART into the social lives of PLWH and HIV-care practices in Senegal. Semi-structured interviews were conducted with 42 PLWH in two hospital care units in Dakar and with 13 healthcare providers and 6 peer educators. Interviews were transcribed, thematically coded and analysed using a cross-sectional approach. We found three key issues. First, simplifying living with HIV: PLWH respondents perceive LAI-ART as an opportunity to ease the burden associated with taking tablets. This enthusiasm may however be qualified by an ambivalent relationship with injections and is subject to certain conditions. Second, certain constraints linked to the medicalisation of care are to be anticipated, including the obligation to go to the hospital every two months for injections. These findings foreshadow the new management work for medical follow-up expected to fall on PLWH and caregivers. Third, the challenges of introducing LAI-ART in Senegal are to ensure adequate organisation of care and supply and sustainability of the program. These results clarify how to implement programs to introduce LAI-ART into real life in the West African context. [ABSTRACT FROM AUTHOR]

Background: We evaluated the impact of the CHORUS™ app on adherence to the cabotegravir and rilpivirine long-acting injectable (CAB + RPV LAI) monthly injections schedule. Methods: Healthcare centers (HCCs) were randomized to access CHORUS™ CAB + RPV LAI features (intervention) or not (control) from 01OCT2021-31JAN2022. Target window adherence (maintenance injections ≤7 days before/after target day) was assessed with multivariate logistic regression (generalized estimating equations). Results: CAB + RPV LAI was administered to 188 and 79 individuals at intervention and control HCCs, respectively. Intervention was not associated with improved target window adherence (adjusted odds ratio: 0.61 [95% CI: 0.30-1.25]). However, app use was associated with increased odds of adherence compared to no app use among all intervention HCCs (2.98 [1.26-7.06]) and at smaller HCCs (3.58 [1.31-9.80]). Conclusions: While access to CHORUS™ CAB + RPV LAI features did not improve target window adherence, app use did, especially at smaller HCCs which may not have established LAI management procedures. Trial registration: https://clinicaltrials.gov/show/NCT04863261. Plain Language Summary: Evaluation of a mobile app and web portal to help with the timely injections of cabotegravir + rilpivirine long-acting injections Cabotegravir + rilpivirine long-acting injectable (CAB+RPV LAI) is the first long-acting regimen for HIV treatment, which was approved in the US in 2021. CAB+RPV LAI should be administered ≤7 days before/after the target date. We conducted a trial to evaluate the impact of the CHORUS™ app and web portal on the timing of monthly CAB+RPV injections. The intervention clinics had access to features designed to help with CAB+RPV LAI management, including flagging delayed/missed injections and appointment scheduling status. Control clinics did not have access to these features and managed CAB+RPV LAI administration on their own. Access to the app and web portal features for intervention clinics had no impact on timing of injections compared to control clinics. However, intervention clinics who actively used the app were close to three times more likely to give injections on-time than intervention clinics who did not use the app. The effect of app use was seen specifically among smaller clinics caring for <1000 people with HIV: smaller clinics that actively used the app were 3.58 times more likely to give injections on-time than those who did not use the app. In conclusion, while access to CHORUS™ CAB+RPV LAI features in the app and the web portal did not improve the likelihood of on time injections, actively using the app did make a difference, especially at smaller clinics which may not have established injection management procedures. [ABSTRACT FROM AUTHOR]

Injectable antiretroviral treatment (ART) represents a new effective and potentially more convenient alternative to oral ART for people living with HIV (PLWH). This study assessed preferences of PLWH for long-acting injectable compared with oral ART in the Netherlands. A labelled discrete choice experiment presented 12 choice sets of long-acting injectable and oral ART. PLWH were asked to select their preferred ART, described by six attributes: location of administration, dosing frequency, risk of short-term side effects, drug–drug interaction, forgivability, and food and mealtime restrictions. Random parameters logit and latent class models were used to estimate preferences of PLWH. 98.6% of 76 respondents were experienced oral ART users that had taken ART for a median of 12 years (Q1–Q3: 7.0–20.0). 30 (39.5%) respondents chose long-acting injectable ART in all choice tasks and 22 (28.9%) always chose oral ART. The random parameter model showed that, on average, respondents significantly favoured long-acting injectable ART over oral ART, preferred administration of the long-acting injectable ART at home, and a less frequent regimen. The latent class model confirmed one class strongly preferring long-acting injectable ART and one class slightly preferring oral ART. This study highlights the value for both long-acting injectable and oral ART. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: HIV pre-exposure prophylaxis (PrEP) is a highly effective method to mitigate the HIV epidemic, but uptake of PrEP has been slow and is associated with racial and gender disparities. Oral PrEP requires high levels of adherence to be effective, which may disadvantage certain high-risk groups. The first injectable HIV PrEP, a drug given every 2 months rather than as a daily pill, was approved by the US Food & Drug Administration in December 2021. Setting: A Family Medicine practice in a single health organization in the United States (November 2022 to February 2023). Methods: We conducted interviews with patients and key stakeholders to characterize factors affecting long-acting injectable (LAI) PrEP implementation. Data collection and analysis were guided by the Consolidated Framework for Implementation Research. Interviews were transcribed and analyzed using guided content analysis. Results: Twenty-five patients (n = 13) and practice stakeholders (n = 12) were interviewed. Overall, stakeholders described a very low uptake of LAI PrEP. Barriers to LAI PrEP included a lack of awareness, insurance and access issues, a lack of streamlined workflow, and a trust in pills over injectables. Facilitators to LAI PrEP implementation included the absence of a pill burden, a culture of shared decision making, and pharmacy support. Conclusions: Although uptake has been slow, we have identified several promising strategies for improving rollout and implementation of LAI PrEP. Approaches that can bolster rollout of LAI PrEP include having an interdisciplinary care team that is supported by PrEP navigators and pharmacists and are informed by a patient-centered model of care to increase patient engagement and trust. [ABSTRACT FROM AUTHOR]

Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first complete injectable antiretroviral for patients living with HIV. To facilitate patient access to long-acting injectable treatment, a system-wide, pharmacist-led, LA-CAB/RPV transition program was developed at four health system-based New York clinics. Provider referrals were received across four clinics between January 22nd, 2021, and December 31st, 2022. All referrals were evaluated by a pharmacist for clinical eligibility and medication access. The primary outcome was the treatment retention rate defined as the percentage of patients who remained on LA-CAB/RPV at 3 months post-transition. A total of 171 referrals were received, with 73 patients (43%) initiating LA-CAB/RPV. Baseline demographics included a median age of 38 years, 81% patients were male, 41% were African American, and 49% had commercial insurance coverage. The treatment retention rate was 90% at 3 months post-transition. By the end of the study period, 84% of patients who transitioned remained on LA-CAB/RPV. Treatment was discontinued due to reasons such as viral breakthrough (4%), emergence of mutations (4%), and intolerable side effects (4%). Injection site reactions were commonly reported (51%), but only resulting in treatment discontinuation for one patient. A pharmacist-led program can transition a diverse population of patients living with HIV to LA-CAB/RPV. Results from this study further add to clinical experiences with LA-CAB/RPV, demonstrating real-world treatment retention despite more frequent clinic visits for patients. [ABSTRACT FROM AUTHOR]

An aripiprazole long-acting injectable (LAI) antipsychotic is now available for gluteal administration every 2 months via two different formulations: aripiprazole lauroxil (AL) and aripiprazole monohydrate (Ari 2MRTU). These longer dosing regimens of aripiprazole LAI offer new potential benefits for patients. The authors review the evidence supporting the efficacy and safety of aripiprazole LAIs given every 2 months for the treatment of schizophrenia or bipolar disorder (BD) in adults. The article culminates with the authors' expert perspectives on the subject. AL 1064 mg every 2 months has established efficacy for the treatment of schizophrenia based on pharmacokinetic bridging studies and prospective data for treatment of an acute exacerbation of schizophrenia. In an open-label trial, Ari 2MRTU showed efficacy for the treatment of schizophrenia and BD type I based on pharmacokinetic parameters (comparable to aripiprazole once-monthly 400 mg); it also showed efficacy regarding the secondary endpoints. Multiple doses of AL 1064 mg or Ari 2MRTU 960 mg are generally well tolerated, in line with the safety profile of oral aripiprazole, with the exception of the injection-site reactions. While AL may require a 1-day initiation regimen, Ari 2MRTU 960 covers all the recommended doses of oral aripiprazole (10–20 mg). [ABSTRACT FROM AUTHOR]

Microneedle (MN) technologies offer the opportunity to improve patient access and target delivery of drugs and vaccines to specific tissues. When in the form of skin patches, MNs can be administered by personnel with minimal training, or could be self-administered by patients, which can improve access to medication, especially those usually requiring injection. Because MNs are small (usually sub-millimetre), they can be used for precise tissue targeting. MN patches have been extensively studied to administer vaccines and drugs in preclinical work as well as in multiple clinical trials. When formulated with biodegradable polymer, MNs can enable long-acting therapies by slowly releasing drug as the MNs biodegrade. Targeted drug delivery by hollow MNs has resulted in FDA-approved products that are able to inject vaccines to skin-resident immune cells to improve immune response and to target specific parts of the eye (e.g., suprachoroidal space) for increased efficacy and avoidance of side effects in other parts of the eye. Cosmetic products based on MN technologies are already in widespread use, mostly as anti-aging agents. With extensive research coupled with FDA-approved products, MN technology promises to continue is growth in research leading to products that can benefit patients. [ABSTRACT FROM AUTHOR]

Objective: To review the efficacy, safety, and role of lenacapavir (LEN) in the treatment of HIV-1 infection. Data Sources: A literature search was performed using PubMed and Google Scholar (through March 2023) with the search term LEN and GS-6207. Other resources included abstracts presented at recent conferences, the manufacturer's Web site, and prescribing information. Study Selection and Data Extraction: All relevant articles, trial updates, and conference abstracts in the English language were included. Data Synthesis: Lenacapavir represents a new class of antiretrovirals (ARVs) with a novel mechanism of action as a capsid inhibitor and a unique twice-a-year subcutaneous administration schedule. Lenacapavir when combined with other ARVs has proven to benefit heavily treatment-experienced (HTE) patients with HIV-1 infection in achieving viral suppression and immune restoration. Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs: Lenacapavir is a new treatment option that patients who are HTE can consider adding as part of an ARV regimen. Conclusions: Lenacapavir is an effective and well-tolerated option for HTE patients which is a valuable addition to the arsenal of ARVs. [ABSTRACT FROM AUTHOR]

Abstract Introduction Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. Objective The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. Methods MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. Results A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. Conclusion LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.

Abstract Introduction The first complete long-acting antiretroviral therapy (ART) regimen, cabotegravir + rilpivirine long-acting (CAB + RPV LA) injectable, was approved in the US for HIV-1 treatment in individuals on a stable antiretroviral regimen with a viral load

Purpose The purpose of this article is to review the pharmacology, efficacy, and safety of the capsid inhibitor lenacapavir for the treatment of multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection. Summary A review of the literature was performed by searching PubMed/MEDLINE for all relevant articles published between February 2021 and March 2023 using the keywords "lenacapavir," "Sunlenca," "human immunodeficiency virus," and "treatment" together with "multidrug resistant human immunodeficiency virus." All English-language articles describing clinical trials assessing the efficacy and safety of lenacapavir when used in humans for the treatment of HIV infection were included. Review articles, conference abstracts, and article references were evaluated for relevant information, and data were also obtained from the manufacturer's website and the package insert. Lenacapavir has been approved by the Food and Drug Administration (FDA) for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistance for whom the current antiretroviral regimen is failing due to resistance, intolerance, or safety considerations. It is the first in a new class of drugs called capsid inhibitors to receive FDA approval. Lenacapavir is a long-acting subcutaneous injectable to be administered once every 6 months. The phase 3 clinical trial evaluating lenacapavir has demonstrated its efficacy in viral load reduction from baseline compared to placebo in patients receiving optimized background therapy. The most common adverse events reported in the clinical trial were injection site reactions, occurring in 63% of participants. Conclusion Lenacapavir is a novel capsid inhibitor indicated, in combination with other antiretroviral therapy, for treatment of multidrug-resistant HIV-1 infection. [ABSTRACT FROM AUTHOR]

Introduction: Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. Objective: The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. Methods: MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. Results: A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. Conclusion: LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation. [ABSTRACT FROM AUTHOR]

Introduction: The first complete long-acting antiretroviral therapy (ART) regimen, cabotegravir + rilpivirine long-acting (CAB + RPV LA) injectable, was approved in the US for HIV-1 treatment in individuals on a stable antiretroviral regimen with a viral load < 50 copies/mL, no treatment failure history, and no resistance to either cabotegravir or rilpivirine. We describe injection schedule adherence and virologic effectiveness of CAB + RPV LA in routine clinical care in the US. Methods: From the OPERA® cohort, all adults with HIV who received their first CAB + RPV LA injection and ≥ 1 continuation injections between 21 January 2021 and 15 March 2022 were included. The injection target date was updated monthly and set to the same date of the month as the previous injection. Continuation injections administered within 7 days before or after the target date were considered on time, as per the label. Virologic undetectability (viral load < 50 copies/mL), suppression (viral load < 200 copies/mL), and confirmed virologic failure (2 consecutive viral loads ≥ 200 copies/mL or 1 viral load ≥ 200 copies/mL followed by discontinuation) were described among individuals with a viral load < 50 copies/mL at initiation and ≥ 1 follow-up viral load. Results: Among 321 individuals on CAB + RPV LA, 90% of the continuation injections were administered on time (within ± 7 days of the target date). Of the 237 individuals with a viral load < 50 copies/mL at initiation and ≥ 1 follow-up viral load, nearly all were undetectable (95%) or suppressed (99%) at their last viral load measurement, 96% maintained virologic suppression with all measured viral loads < 200 copies/mL, and four confirmed virologic failures were observed. Injection delays were infrequent, and did not affect virologic outcomes over the short term. Conclusion: In this large US cohort, most monthly CAB + RPV LA injections were administered on time and high levels of virologic control were achieved. These results suggest that CAB + RPB LA injectable can be administered effectively during routine clinical care. [ABSTRACT FROM AUTHOR]

Multiple studies report racial disparities in antipsychotic prescription patterns. This study assessed demographic and clinical factors associated with the utilization of first-generation (FG) versus second-generation (SG) long-acting injectable (LAI) antipsychotics. This retrospective, observational cohort analysis used claims data from the IBM MarketScan® Multi-State Medicaid database. The study included adults with an LAI claim between 01-January-2009 and 31-December-2018, an ICD-9-CM or ICD-10-CM diagnosis of schizophrenia, race recorded as Black or White, and ≥12 months of continuous enrollment before the index LAI. Descriptive analysis detailed the relationship between race and FG or SG LAI initiation. Multivariate logistic regression was used to assess potential associations with FG vs. SG LAI initiation, including clinical and demographic factors, comorbidities, and index year. A total of 10,773 patients were included: 6659 (62 %) Black and 4114 (38 %) White. Black patients had a higher utilization of FG LAIs than White patients (46.8 % vs. 38.9 %) over the 10 years analyzed. Black patients were more likely to utilize FG LAIs than White patients (odds ratio: 1.47; 95 % CI: 1.34, 1.62) after controlling for index year and covariates (race, age, gender, insurance plan type, Quan-Charlson Comorbidity index score, comorbidities, prior medications). Significant predictors of FG LAI utilization were older age, type of baseline oral antipsychotic (FG vs SG), type of coverage (managed care vs fee for service), and greater comorbidity burden. The utilization of FG LAIs was greater in Black compared to White Medicaid beneficiaries with schizophrenia over a 10-year period. These findings suggest that racial disparities exist in LAI initiation, with implications for differential quality of schizophrenia treatment. [ABSTRACT FROM AUTHOR]

Long-acting injectable (LAI) modalities have been developed for ART and PrEP. Women face unique barriers to LAI use yet little research has examined women's perceptions of potential LAI HIV therapy candidates. We conducted 89 in-depth interviews at six Women's Interagency HIV Study (WIHS) sites with women living with HIV (n = 59) and HIV-negative women (n = 30) from 2017 to 2018. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Participants identified specific sub-populations who could most benefit from LAI over daily pills: (1) young people; (2) women with childcare responsibilities; (3) people with adherence-related psychological distress; (4) individuals with multiple sex partners; and (5) people facing structural insecurities such as homelessness. Women are underserved by current HIV care options and their perspectives are imperative to ensure a successful scale-up of LAI PrEP and LAI ART that prioritizes equitable access and benefit for all individuals.

Introduction: Long-acting injectable antipsychotics (LAI-As) are important tools for the treatment of schizophrenia, yet they appear to be underutilized. This study will assess practitioner perceptions of LAI-As to elucidate reasons for underuse and uncover new avenues to increase appropriate use. Methods: An anonymous electronic survey was developed and actively distributed to behavioral health care practitioners (MD, DO, PA, NP, PharmD, RN, LCSW). Independent t testing and linear regression analysis was used to assess for interactions between survey responses and individual factors. Results: A total of 146 survey responses were collected from September 3, 2020 to March 17, 2021. On average, participants thought that LAI-As were slightly underutilized in practice. The mean estimated patient acceptance rate for LAI-A therapy was 38.6% ± 29.5% (range = 0%-100%). Participants who were

Abstract Background Long-acting injectable formulations for HIV infection have been approved and are now available in Japan. Although not currently recommended as first-line drugs in Japanese or overseas guidelines, use of such formulations may increase, in accordance with patient conditions and preference. We determine the level of satisfaction with current anti-HIV drugs and analyzed the preferences of patients who favor long-acting injectable drugs based on their satisfaction level with the present anti-HIV drugs. Methods People living with HIV (PLWH) who had received antiretroviral therapy (ART) for at least one month and consented to the study between 1 April and 31 December 2021 were included in a survey conducted using a self-administered questionnaire. The content of the survey included satisfaction with seven items (tablet size, ease and feeling when taking the medicine, color, taste, portability, daily oral therapy, and co-payment) related to the anti-HIV drugs they were taking and their need for future drugs (dosage form, frequency of dosing, long-acting injectable, etc.). In addition, factors related to the need for long-acting injectable medications were analyzed with regard to the relationship with satisfaction with anti-HIV drugs. Results Overall, 667 patients available for analysis were included in this study. Satisfaction with anti-HIV drugs was highest with regard to “co-payment” and lowest with “daily oral therapy”. Regarding the need for long-acting injectable medications, logistic regression analysis indicated that tablet size and daily oral therapy were significant predictors of patient preference for a once-every-eight-weeks intramuscular formulation in terms of their requirement for long-acting injectable medications (tablet size, OR = 2.14, 95%CI 1.030–4.430, p = 0.042; and daily oral therapy, OR = 1.75, 95%CI 1.010–3.030, p = 0.044). Conclusions Patients currently receiving anti-HIV drugs who express dissatisfaction with tablet size and daily oral therapy may prefer a long-acting injectable formulation, taking into consideration patient age, employment status, ART history, frequency of daily dosage and concomitant medications other than ART.

In situ depot gel is a type of polymeric long-acting injectable (pLAI) drug delivery system; compared to microsphere technology, its preparation process is simpler and more conducive to industrialization. To ensure the chemical stability of peptide ACTY116, we avoided the use of harsh conditions such as high temperatures, high shear mixing, or homogenization; maintaining a water-free and oxygen-free environment was also critical to prevent hydrolysis and oxidation. Molecular dynamics (MDs) simulations were employed to assess the stability mechanism between ACTY116 and the pLAI system. The initial structure of ACTY116 with an alpha helix conformation was constructed using SYBYL-X, and the copolymer PLGA was generated by AMBER 16; results showed that PLGA-based in situ depot gel improved conformational stability of ACTY116 through hydrogen bonds formed between peptide ACTY116 and the components of the pLAI formulation, while PLGA (Poly(DL-lactide-co-glycolide)) also created steric hindrance and shielding effects to prevent conformational changes. As a result, the chemical and conformational stability and in vivo long-acting characteristics of ACTY116 ensure its enhanced efficacy. In summary, we successfully achieved our objective of developing a highly stable peptide-loaded long-acting injectable (LAI) in situ depot gel formulation that is stable for at least 3 months under harsh conditions (40 °C, above body temperature), elucidating the underlying stabilisation mechanism, and the high stability of the ACTY116 pLAI formulation creates favourable conditions for its in vivo pharmacological activity lasting for weeks or even months.

Joshua Barnett,1 Sofia Pappa1,2 1Department of Mental Health, West London NHS Trust, London, UK; 2Department of Brain Sciences, Imperial College London, London, UKCorrespondence: Joshua Barnett, Department of Mental Health, West London NHS Trust, 43– 47 Avenue Road, London, W38NJ, UK, Tel +44 20 84831792, Email joshua.barnett2@nhs.netIntroduction: Poor adherence to antipsychotic medication is common in the treatment of schizophrenia and other psychotic disorders. Paliperidone palmitate 3-monthly (PP3M) is the first long-acting injectable (LAI) antipsychotic to allow for only four medication administrations per year, and although there is sufficient information available about the clinical effects, there is relatively limited insight into the subjective experience of people with lived experience.Methods: This descriptive, cross-sectional survey explored patient’s satisfaction and perspectives on the advantages and disadvantages of switching from monthly to 3-monthly paliperidone while also reporting on perceived levels of safety with regard to the reducing dose regimen during the Covid-19 pandemic. Information on discontinuation and hospitalisation rates at one year was also collected from the electronic records.Results: Of the 46 patients included in the study, the vast majority reported feeling satisfied (89.2%) and safer (93.5%) after switching to the three-monthly formulation. Participants highlighted several advantages of changing to PP3M, most notably convenience (93.5%), improved quality of life (58.7%), decreased stigma (39.1%) and better adherence (28.3%). Furthermore, 93.5% of respondents experienced no disadvantages, while 6.5% described worsening side effects or symptoms. In fact, only one patient discontinued PP3M at one year with the overall number of hospitalisations also reducing in the same period compared to the year before switching.Discussion: Our findings add to the small, but growing, body of evidence supporting patient satisfaction and acceptance with the use of PP3M and may reinforce the use of less frequent LAIs in clinical practice to enhance individual experience and treatment persistence and decrease levels of stigmatisation.Keywords: schizophrenia, paliperidone, long-acting injectable, patient satisfaction

Introduction Long-acting injectable (LAI) antipsychotics are a promising solution to combating issues related to nonadherence to oral antipsychotics. Oral overlap is utilized when an LAI is initiated to achieve therapeutic concentrations. The place in therapy in which additional overlap is warranted is often mistaken, and providers may prescribe additional overlap based on the presentation of the patient or misunderstanding of appropriate overlap. Methods This retrospective chart review assesses patients who were initiated on an LAI while admitted to the acute inpatient psychiatric unit from January 1, 2016, to December 31, 2019. The primary outcome assesses the appropriateness of oral overlap with LAIs. Secondary outcomes include adherence to oral overlap, discontinuation of an LAI within 4 months, and reason for discontinuation of LAI. Results A total of 62 patients were included: 40 (65%) had appropriate overlap, and 22 (35%) had inappropriate overlap. The most common LAI was paliperidone (n = 50, 81%). Patients were adherent to oral overlap in 67% (n = 6) of the appropriate overlap group and 85% (n = 17) of the inappropriate overlap group. Discontinuation of an LAI in 4 months occurred in 62.5% (n = 25) of the appropriate group and 40.9% (n = 9) of the inappropriate group. There were no significant differences in secondary outcomes when comparing adherence to oral overlap (p = .26), discontinuation of LAI within 4 months (p = .62), and reason for discontinuation (p = .69). Discussion This study identified that a majority of patients had appropriate prescribing of oral antipsychotic overlap.

Abstract Background Schizophrenia is mostly a chronic disorder whose symptoms include psychosis, negative symptoms and cognitive dysfunction. Poor adherence is common and related relapse can impair outcomes. Long-acting injectable antipsychotics (LAIs) may promote treatment adherence and decrease the likelihood of relapse and rehospitalization. Using LAIs in first-episode psychosis (FEP) and early-phase (EP) schizophrenia patients could benefit them, yet LAIs have traditionally been reserved for chronic patients. Methods A three-step modified Delphi panel process was used to obtain expert consensus on using LAIs with FEP and EP schizophrenia patients. A literature review and input from a steering committee of five experts in psychiatry were used to develop statements about patient population, adverse event management, and functional recovery. Recruited Delphi process psychiatrists rated the extent of their agreement with the statements over three rounds (Round 1: paper survey, 1:1 interview; Rounds 2–3: email survey). Analysis rules determined whether a statement progressed to the next round and the level of agreement deemed consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists assess their previous responses in the context of those of the overall group. Results The Delphi panelists were 17 psychiatrists experienced in treating schizophrenia with LAIs, practicing in seven countries (France, Italy, US, Germany, Spain, Denmark, UK). Panelists were presented with 73 statements spanning three categories: patient population; medication dosage, management, and adverse events; and functional recovery domains and assessment. Fifty-five statements achieved ≥ 80% agreement (considered consensus). Statements with low agreement (40-79%) or very low agreement (

Matthew Harlin,1,&ast; Craig Chepke,2,3,&ast; Frank Larsen,4,&ast; Karimah S Bell Lynum,5,&ast; Sanjeda R Chumki,5,&ast; Heather Fitzgerald,6,&ast; Pedro Such,7,&ast; Jessica Madera-McDonough,8,&ast; Murat Yildirim,7,&ast; Moeen Panni,8,&ast; Stephen R Saklad9,&ast; 1Quantitative Pharmacology, Clinical Pharmacology, Early Phase & Translational Medicine, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA; 2Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC, USA; 3Excel Psychiatric Associates, Huntersville, NC, USA; 4Pharmacokinetic and Pharmacodynamic Modelling & Simulation, H. Lundbeck A/S, Valby, Denmark; 5US Medical Affairs, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA; 6Medical Affairs, Lundbeck LLC, Deerfield, IL, USA; 7Medical Affairs, H. Lundbeck A/S, Valby, Denmark; 8Global Medical Affairs, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA; 9Division of Pharmacotherapy, College of Pharmacy, The University of Texas at Austin, San Antonio, TX, USA&ast;These authors contributed equally to this workCorrespondence: Matthew Harlin, Otsuka Pharmaceutical Development & Commercialization Inc., 508 Carnegie Center Dr, Princeton, NJ, 08540, USA, Tel +1-240-683-3055, Email Matthew.Harlin@otsuka-us.comAbstract: Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a novel long-acting injectable (LAI) formulation of aripiprazole monohydrate for administration once every 2 months, developed for the treatment of schizophrenia or maintenance monotherapy treatment of bipolar I disorder in adults (indication will vary by country). Aripiprazole lauroxil 1064 mg (AL 1064) is an LAI formulation of aripiprazole lauroxil, an aripiprazole prodrug, for administration once every 2 months, indicated for the treatment of schizophrenia in adults. This analysis provides an indirect comparison of aripiprazole plasma concentrations following multiple doses of either formulation. Clinical trial data were used to determine average steady-state aripiprazole plasma concentration (Cavg,ss), maximum aripiprazole plasma concentration (Cmax), and other pharmacokinetic parameters of either formulation following four administrations (96 patients received Ari 2MRTU 960; 28 patients received AL 1064). All pharmacokinetic parameters were considered in the context of a minimum aripiprazole therapeutic concentration (Cmin) of ≥ 95 ng/mL. An exposure–response analysis using data from two Phase III trials of aripiprazole once-monthly (an aripiprazole monohydrate LAI, administered monthly), showed that patients with a Cmin ≥ 95 ng/mL are 4.41 times less likely to relapse than patients with a Cmin < 95 ng/mL. A similar analysis has not been performed for AL 1064. However, consensus guidelines for therapeutic drug monitoring recommend a range of 100– 350 ng/mL for aripiprazole. Following four administrations, mean (standard deviation [SD]) Cavg,ss over the 2-month dosing interval was 263 (133) ng/mL for Ari 2MRTU 960 and 140.7 (57.3) ng/mL for AL 1064. Mean (SD) Cmax during the fourth dosing interval was 342 (157) ng/mL for Ari 2MRTU 960 and 188.8 (79.8) ng/mL for AL 1064. This indirect comparison showed that, following four administrations, Ari 2MRTU 960 and AL 1064 delivered mean aripiprazole plasma concentrations that remained above the minimum therapeutic concentration of aripiprazole over the 2-month dosing interval.Keywords: antipsychotic, bipolar I disorder, long-acting injectable, schizophrenia

Abstract Background Functional impairment affects many patients with schizophrenia. Treatment with the long-acting injectable antipsychotic aripiprazole once-monthly (AOM) may help improve functioning. Objectives To explore changes in functioning in patients with schizophrenia who received AOM treatment in observational studies. Methods Here we report functional outcomes in the form of Global Assessment of Functioning (GAF) scores in a pooled analysis of data from two observational studies from Canada (NCT02131415) and Germany (vfa non-interventional studies registry 15960N). Data from 396 patients were analyzed. Results At baseline, the mean GAF score was 47.7 (SD 13.4). During 6 months of treatment with AOM, the mean GAF score increased to 59.4 (SD 15.8). Subgroups stratified by patient age (≤35 years/>35 years), sex, disease duration (≤5 years/>5 years) and disease severity at baseline had all significantly improved their GAF at month 6. 51.5% of the patients showed a GAF score increase of at least 10 points, which was regarded as clinically meaningful, and were considered responders. Conclusions These data show that treatment with AOM may help improve patient functioning in a routine treatment setting. Trial registration NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N.

Abstract Background The therapeutic decision toward patients with schizophrenia is very different from one psychiatrist to another when faced with potentially similar clinical symptoms. It depends on many factors that are related to the patient’s and the doctor’s profiles, and the drug’s characteristics. To date, no study has been conducted in Morocco on the prescribing habits of psychiatrists toward patients with schizophrenia. The objectives of our survey are to identify the molecules most prescribed by psychiatrists in Morocco for patients with schizophrenia and to determine the most common therapeutic strategies. Results Our survey recruited 72 Moroccan psychiatrists. The median age was 36.5 years. 72.2% were women, and 37.5% had between 5 and 10 years of practice. More than two-thirds were practicing in the public sector in big cities. Olanzapine was an antipsychotic prescribed as first-line treatment for a patient with schizophrenia. For the majority, the most frequent combination was atypical antipsychotics with conventional neuroleptics. On the one hand, most psychiatrists reported prescribing neuroleptics long-acting injectable (neuroleptic LAIs). In the other hand, almost half of the participants had never prescribed second-generation antipsychotic long-acting injectables (SGA-LAIs). The high cost (77.8%), lack of availability of the product in certain sectors (33.3%), lack of therapeutic choice (26.4%), and lack of patient profile that could use the drug (23.6%), were among the strong reasons given for not prescribing SGA-LAIs. Conclusions The treatment decision for patients with schizophrenia differs from one clinician to the other. It depends on various factors that may be related to the psychiatrist, the patient, and to the drug.

AIDS (acquired immunodeficiency syndrome) is a potentially life-threatening infectious disease caused by human immunodeficiency virus (HIV). To date, thousands of people have lost their lives annually due to HIV infection, and it continues to be a big public health issue globally. Since the discovery of the first drug, Zidovudine (AZT), a nucleoside reverse transcriptase inhibitor (NRTI), to date, 30 drugs have been approved by the FDA, primarily targeting reverse transcriptase, integrase, and/or protease enzymes. The majority of these drugs target the catalytic and allosteric sites of the HIV enzyme reverse transcriptase. Compared to the NRTI family of drugs, the diverse chemical class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) has special anti-HIV activity with high specificity and low toxicity. However, current clinical usage of NRTI and NNRTI drugs has limited therapeutic value due to their adverse drug reactions and the emergence of multidrug-resistant (MDR) strains. To overcome drug resistance and efficacy issues, combination therapy is widely prescribed for HIV patients. Combination antiretroviral therapy (cART) includes more than one antiretroviral agent targeting two or more enzymes in the life cycle of the virus. Medicinal chemistry researchers apply different optimization strategies including structure- and fragment-based drug design, prodrug approach, scaffold hopping, molecular/fragment hybridization, bioisosterism, high-throughput screening, covalent-binding, targeting highly hydrophobic channel, targeting dual site, and multi-target-directed ligand to identify and develop novel NNRTIs with high antiviral activity against wild-type (WT) and mutant strains. The formulation experts design various delivery systems with single or combination therapies and long-acting regimens of NNRTIs to improve pharmacokinetic profiles and provide sustained therapeutic effects. [ABSTRACT FROM AUTHOR]

Objective: The aim is to assess the impact of long-acting buprenorphine (LAI-BNP) on frequency of methamphetamine (MA) use. Methods: We undertook an observational, descriptive, retrospective cohort study of patients of a public, tertiary, community-based Alcohol and Other Drug Service (AODS) with opioid use disorder (OUD) treated with LAI-BNP who are current or past users of MA. We assessed the changes of frequency of use in their MA use at start (baseline), 3 and 6 months of LAI-BNP. Results: Study included 59 participants. Based on their MA use at the commencement of LAI-BNP, the sample was further sub-grouped as active users (n = 30) and past users (n = 29). At 6 months of LAI-BNP, all the past users remained abstinent from MA use. 70% (n = 21) of participants with active MA use had reduced or ceased their MA use while 17% (n = 5) increased their MA use at 6 months. Conclusions: The results favour the use of LAI-BNP as a potential treatment for MA use. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this project is to assess the time‐to‐therapy discontinuation and hospital readmission rate among patients newly diagnosed with schizophrenia who are prescribed long‐acting injectable versus oral dopamine receptor blocking agents. Methods: A retrospective review of medical records was performed for adult patients admitted to an 80‐bed inpatient behavioural health facility with a new diagnosis of schizophrenia. The primary outcome studied was time to therapy discontinuation within 1 year of discharge, while secondary outcomes assessed were time‐to‐therapy discontinuation within 90 days and readmission rate at 30‐days, 6 months, and 1 year. Multivariate Cox proportional hazard and linear regression modelling were used for statistical analysis. Results: A total of 425 patients were included in the analysis, with 66.4% (n = 282) discharged on oral and 33.6% (n = 143) on long‐acting injectable dopamine receptor blocking agents. At 1 year post‐discharge, the rates of discontinuation were 49.7% for those prescribed long‐acting injectable and 55.7% for those prescribed oral formulations (adjusted hazard ratio = 0.54, p =.012). There was no statistically significant difference in readmission rate between the patients prescribed long‐acting injectable and oral dopamine receptor blocking agents at any timepoint tested. Conclusions: The use of long‐acting injectable dopamine receptor blocking agents was associated with longer time‐to‐discontinuation compared to oral agents when prescribed to patients newly diagnosed with schizophrenia in the inpatient setting. However, this was not associated with significant reductions in rehospitalization, calling into question the clinical impact. Future studies will seek to confirm these findings using a prospective study design. [ABSTRACT FROM AUTHOR]

Background: Long-acting injectable formulations for HIV infection have been approved and are now available in Japan. Although not currently recommended as first-line drugs in Japanese or overseas guidelines, use of such formulations may increase, in accordance with patient conditions and preference. We determine the level of satisfaction with current anti-HIV drugs and analyzed the preferences of patients who favor long-acting injectable drugs based on their satisfaction level with the present anti-HIV drugs. Methods: People living with HIV (PLWH) who had received antiretroviral therapy (ART) for at least one month and consented to the study between 1 April and 31 December 2021 were included in a survey conducted using a self-administered questionnaire. The content of the survey included satisfaction with seven items (tablet size, ease and feeling when taking the medicine, color, taste, portability, daily oral therapy, and co-payment) related to the anti-HIV drugs they were taking and their need for future drugs (dosage form, frequency of dosing, long-acting injectable, etc.). In addition, factors related to the need for long-acting injectable medications were analyzed with regard to the relationship with satisfaction with anti-HIV drugs. Results: Overall, 667 patients available for analysis were included in this study. Satisfaction with anti-HIV drugs was highest with regard to "co-payment" and lowest with "daily oral therapy". Regarding the need for long-acting injectable medications, logistic regression analysis indicated that tablet size and daily oral therapy were significant predictors of patient preference for a once-every-eight-weeks intramuscular formulation in terms of their requirement for long-acting injectable medications (tablet size, OR = 2.14, 95%CI 1.030–4.430, p = 0.042; and daily oral therapy, OR = 1.75, 95%CI 1.010–3.030, p = 0.044). Conclusions: Patients currently receiving anti-HIV drugs who express dissatisfaction with tablet size and daily oral therapy may prefer a long-acting injectable formulation, taking into consideration patient age, employment status, ART history, frequency of daily dosage and concomitant medications other than ART. [ABSTRACT FROM AUTHOR]

Background Paliperidone palmitate 6-month (PP6M) demonstrated noninferiority to paliperidone palmitate 3-month in preventing relapse in patients with schizophrenia in a phase 3 double-blind (DB) study (NCT03345342). Here, we report long-term efficacy and safety results from a 2-year single-arm, open-label extension (OLE; NCT04072575) of this DB study. Methods Participants who completed the DB study without relapse were enrolled and followed-up every 3 months up to 2 years. Participants received 4 PP6M gluteal injections (700/1000 mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included assessment of relapse, Positive and Negative Syndrome Scale total score, Personal and Social Performance score, and Clinical Global Impression-Severity scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations, and laboratory tests. Results Of 178 participants enrolled, 154 (86.5%) completed the OLE (mean age: 40.4 years, men: 70.8%; mean duration of PP6M exposure during OLE: 682.1 days). Overall, 7/178 (3.9%) participants relapsed between 20 and 703 days after enrolment. Mean (SD) changes from baseline to endpoint were as follows: Positive and Negative Syndrome Scale total score, 0.7 (8.22); Clinical Global Impression-Severity, 0.0 (0.51); and Personal and Social Performance Scale, 0.5 (7.47). Overall, 111/178 participants (62.4%) reported ≥1 TEAE; most common (>5%) TEAEs were headache (13.5%) and increased blood prolactin/hyperprolactinemia (18.0%); 8/178 (4.5%) participants experienced serious TEAEs, and 6/178 (3.4%) participants withdrew due to TEAEs. No deaths were reported. Conclusions The relapse rate observed with PP6M during the 2-year OLE was low (3.9%). Clinical and functional improvements demonstrated in the DB study were maintained during OLE, and no new safety concerns were identified. Trial registration ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30. [ABSTRACT FROM AUTHOR]

Cesar Giron‐Hernandez,1 Joong Hee Han,2 Roberta Alberio,3 Arun Singh,2 Maria Paz García-Portilla,4 Maurizio Pompili,5 R Karl Knight,2 Ute Richarz,6 Srihari Gopal,2,7 José Antunes8 1EMEA Medical Affairs, Janssen-Cilag, Issy-les-Moulineaux, France; 2Janssen Research & Development, LLC, Titusville, NJ, USA; 3Medical Affairs, Janssen-Cilag, Milan, Italy; 4Department of Psychiatry, Universidad de Oviedo, Instituto Sanitario Del Principado de Asturias (ISPA) and CIBERSAM, Oviedo, Spain; 5Department of Neurosciences, Mental Health, and Sensory Organs, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy; 6Janssen Global Services LLC, Cilag Int., Zug, Switzerland; 7Regeneron Pharmaceuticals, Tarrytown, NY, USA; 8EMEA Medical Affairs, Janssen-Cilag, Porto Salvo, PortugalCorrespondence: José Antunes, EMEA Medical Affairs, Janssen-Cilag, Porto Salvo, Portugal, Email jantune1@its.jnj.comPurpose: To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M).Methods: This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq. or 1000 mg eq.) or PP3M (350 mg eq. or 525 mg eq.) in the 12-month DB phase. Primary endpoint was time-to-relapse during the DB phase, using a Kaplan–Meier cumulative survival estimate (non-inferiority margin 95% CI lower bound larger than prespecified as − 10%). Treatment emergent adverse events (TEAEs), physical examinations, and laboratory tests were also evaluated.Results: A total of 384 patients who entered the DB phase were included in European sites (PP6M, n = 260; PP3M, n = 124) with a mean age similar in both groups (mean age [SD] years: PP6M, 40.0 [11.39]; PP3M, 38.8 [10.41]). Baseline characteristics were similar across both groups. The number of patients who experienced a relapse during DB phase were PP6M: 18 (6.9%) vs PP3M: 3 (2.4%) with percentage relapse-free difference of − 4.9% (95% CI: − 9.2%, − 0.5%), thus achieving non-inferiority criteria. Secondary efficacy endpoints indicated comparable improvements. Incidence of TEAEs was similar between PP6M (58.8%) and PP3M (54.8%) groups. Nasopharyngitis, headache, increased weight, and injection-site pain were the most common TEAEs.Conclusion: The efficacy of PP6M was non-inferior to that of PP3M in preventing relapse in the European subgroup previously treated with PP1M or PP3M, which was consistent with the global study. No new safety signals were identified.Keywords: Europe, long-acting injectable, paliperidone palmitate 6-month, relapse-free, schizophrenia

Mingjun Zhao,1,&ast; Bin Qin,2,&ast; Yage Mao,3 Yang Zhang,4 Ruisheng Zhao,5 Aiqin Wang,1 Hailing Wang,1 Jianting Zhao,6 Changhong Wang7 1Department of Pharmacy, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang, People’s Republic of China; 2Department of Neurology, Liuzhou General Hospital, Liuzhou, People’s Republic of China; 3Department of Pharmacy, Maternal and Child Health Care hospital of Xinxiang City, Xinxiang, People’s Republic of China; 4Department of Respiratory, The People’s Hospital of Jiaozuo City, Jiaozuo, People’s Republic of China; 5Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China; 6Department of Neurology, Central Hospital of Xinxiang City, Xinxiang, People’s Republic of China; 7Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changhong Wang, Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), 207&num; QianJin Road, Xinxiang, Henan, 453000, People’s Republic of China, Tel +86-373-3388798, Fax +86-373-3374082, Email wangchdr@163.comPurpose: The aim of this study was to assess the efficacy and safety of paliperidone palmitate (PP) treatment compared with risperidone long-acting injectable (LAI) treatments for patients with schizophrenia.Patients and Methods: Data mining was conducted in April 2022 across PubMed, Web of Science, Embase, the Cochrane Library, ClinicalTrials.gov, and PsycINFO. All published randomized controlled trials (RCTs) that assessed the effect of PP treatment for patients with schizophrenia when compared with the risperidone-LAIAs group were included. Relevant data were extracted and synthesized narratively. Results were expressed as standardized mean differences (SMDs) or risk ratios (RRs), with 95% confidence intervals (CIs).Results: Four RCTs with 2451 patients met all the inclusion and exclusion criteria. Efficacy analyses showed no significant statistical differences in Positive and Negative Syndrome Scale (PANSS) total score changes at the endpoint (SMD = 0.10, P = 0.19), or in response rates (RR = 0.93; P = 0.40). Regarding the safety outcomes, PP treatment showed significantly increased risks of discontinuation rates for any reason (35.7% vs 30.4%; RR = 1.19; 95% CI, 1.03 to 1.39; P = 0.02) and nonsignificantly increased risks of total treatment emergent adverse events (TEAEs) (66.6% vs.64.8%; RR = 1.01; 95% CI, 0.94 to 1.09; P = 0.78) compared with the risperidone-LAIAs-treated group. Furthermore, PP may significantly increase total discontinuation rates compared with risperidone-LAIAs.Conclusion: Our meta-analysis did not find a more beneficial effect of PP compared to risperidone-LAIAs treatments for schizophrenia. Clinicians should interpret and translate our data with caution, as the meta-analysis was based on a limited number of randomized controlled trials and patients.Keywords: paliperidone palmitate, risperidone, long-acting injectable, schizophrenia, meta-analysis

Abstract Background Patients with schizophrenia may benefit from treatment with long-acting injectable (LAI) formulations of antipsychotics. Aripiprazole once-monthly (AOM) is an LAI that was tested in two non-interventional studies in Germany and Canada. Methods Here, we report on analyses of pooled data from the two non-interventional studies. Patients were treated with AOM under real-life conditions. Data were analyzed for a timeframe of 6 months. We analyzed data on Brief Psychiatric Rating Scale (BPRS) domains and items, BPRS total scores in various patient subgroups (male vs. female patients, patients with disease duration ≤ 5 years and > 5 years, patients with different levels of disease severity at baseline), Clinical Global Impression – Improvement (CGI-I) ratings for the total population and subgroups, and comorbidities for the total population. Results Data from 409 patients were included. 65.5% of the patients had comorbidities. Improvements were found in all BPRS domains and items. Furthermore, improvements were similar for male and female patients, patients with disease duration ≤ 5 years and > 5 years, and across different levels of disease severity at baseline. Numerically, more favorable results were found for younger patients, female patients, and those with shorter disease duration. Conclusions AOM can be an effective treatment in the broad range of patients, across sexes, regardless of patient age and duration of disease, independently of disease severity, and across symptoms. Trial registration NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N.

Ruth Milz,1 Carmela Benson,1 Karl Knight,1 Jose Antunes,2 Dean Najarian,3 Paola-Maria Lopez Rengel,4 Steven Wang,1 Ute Richarz,5 Srihari Gopal,1 John M Kane6,7 1Janssen Research & Development LLC, Titusville, NJ, USA; 2Janssen-Cilag, Porto Salvo, Portugal; 3Janssen Scientific Affairs, LLC, Raritan, NJ, USA; 4Janssen Cilag, Madrid, Spain; 5Janssen Global Medical Affairs, Cilag, Zug, Switzerland; 6Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Queens, NY, USA; 7Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USACorrespondence: Ruth Milz, Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA, Email rmilz@ITS.JNJ.comAbstract: Medication nonadherence in schizophrenia can have serious implications including relapses and hospitalization. Long-acting injectable (LAI) antipsychotics require fewer administrations, while ensuring sustained medication coverage. In this review, we summarize the expected real-world benefits of longer dosing intervals in the management of schizophrenia. LAIs are associated with improved clinical outcomes of less frequent relapses and reduced functional impairment, encouraging patients to regain control of their lives. Aripiprazole lauroxil and paliperidone palmitate three-monthly (PP3M) LAIs have longer dosing intervals of 2– 3 months and provide improved outcomes in patients with schizophrenia. Paliperidone palmitate six-monthly (PP6M) LAI provides the longest dosing interval, twice-yearly dosing, among existing LAIs. Decreasing the frequency of LAI administrations has the potential to reduce occurrence of serious outcomes associated with poor medication adherence. By eliminating the need for daily oral antipsychotic dosing, LAIs could increase the likelihood of patient acceptance, decrease stigma, and promote self-esteem. Longer intervals of medication coverage may be desirable for patients with higher risk of relapse including adults with recent-onset schizophrenia, those living in circumstances that may deprive them of regular access (eg, homeless), those that are in transitions between care settings or to reduce interpersonal contact during public health emergencies (eg, COVID-19 pandemic).Keywords: adherence, long-acting injectable, paliperidone palmitate, schizophrenia

Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable antipsychotic formulation for administration every 2 months. A 32-week trial evaluated the safety, tolerability, and pharmacokinetics of Ari 2MRTU 960 in clinically stable adults with schizophrenia or bipolar I disorder (BP-I) (per DSM-5 criteria). This secondary analysis evaluated the safety and efficacy of Ari 2MRTU 960 in the subpopulation of patients with BP-I. Patients with BP-I were randomized to receive Ari 2MRTU 960 (n = 40) every 56 ± 2 days (4 injections scheduled) or aripiprazole once-monthly 400 mg (AOM 400; n = 41) every 28 ± 2 days (8 injections scheduled). Data were collected during August 2019–July 2020 across 16 US sites. Primary safety endpoints included reported adverse events (coded by the Medical Dictionary for Regulatory Activities preferred term), injection site reactions (assessments included a Visual Analog Scale [VAS] to evaluate patient-reported injection-site pain), and motoric symptoms. Secondary endpoints for efficacy included change from baseline at Week 32 in the Young Mania Rating Scale (YMRS), Montgomery–Åsberg Depression Rating Scale (MADRS), Clinical Global Impression – Bipolar Version (CGI-BP), and Subjective Well-being under Neuroleptic Treatment – Short Form (SWN-S) scores, and Clinical Global Impression – Improvement (CGI-I) at Week 32. The incidence of treatment-emergent adverse events (TEAEs) was similar between Ari 2MRTU 960 (82.5% [33/40]) and AOM 400 (87.8% [36/41]; p =.5468). The most frequently reported TEAE was increased weight (Ari 2MRTU 960: 25.0% [10/40]; AOM 400: 26.8% [11/41]; p = 1). Injection-site pain was experienced by more patients in the Ari 2MRTU 960 group (25% [10/40]) versus the AOM 400 group (7.3% [3/41]; p =.0622). Mean (standard deviation [SD]) VAS scores for patient-reported injection-site pain following the last injection were 1.2 (2.07) for Ari 2MRTU 960 group and 1.3 (2.19) for AOM 400 (p =.9479) (VAS scale range 0–100 [no pain–extreme pain]). No notable improvement or decline from baseline was observed in motoric symptoms in either treatment group. Patients in both treatment groups remained clinically stable for the entire 32-week trial duration, with minimal difference between treatment groups in the least squares (LS) mean change from baseline at Week 32 in the YMRS Total (p =.8995), MADRS Total (p =.3185), and CGI-BP scores (p =.8485), and in mean CGI-I score (p =.7960). LS mean change from baseline in SWN-S score was greater for Ari 2MRTU 960 than for AOM 400 at Week 32 (p =.0169). Ari 2MRTU 960 was well tolerated in patients with BP-I, with efficacy similar to AOM 400. ClinicalTrials.gov identifier: NCT04030143. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is mostly a chronic disorder whose symptoms include psychosis, negative symptoms and cognitive dysfunction. Poor adherence is common and related relapse can impair outcomes. Long-acting injectable antipsychotics (LAIs) may promote treatment adherence and decrease the likelihood of relapse and rehospitalization. Using LAIs in first-episode psychosis (FEP) and early-phase (EP) schizophrenia patients could benefit them, yet LAIs have traditionally been reserved for chronic patients. Methods: A three-step modified Delphi panel process was used to obtain expert consensus on using LAIs with FEP and EP schizophrenia patients. A literature review and input from a steering committee of five experts in psychiatry were used to develop statements about patient population, adverse event management, and functional recovery. Recruited Delphi process psychiatrists rated the extent of their agreement with the statements over three rounds (Round 1: paper survey, 1:1 interview; Rounds 2–3: email survey). Analysis rules determined whether a statement progressed to the next round and the level of agreement deemed consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists assess their previous responses in the context of those of the overall group. Results: The Delphi panelists were 17 psychiatrists experienced in treating schizophrenia with LAIs, practicing in seven countries (France, Italy, US, Germany, Spain, Denmark, UK). Panelists were presented with 73 statements spanning three categories: patient population; medication dosage, management, and adverse events; and functional recovery domains and assessment. Fifty-five statements achieved ≥ 80% agreement (considered consensus). Statements with low agreement (40-79%) or very low agreement (< 39%) concerned initiating dosage in FEP and EP patients, and managing loss of efficacy and breakthrough episodes, reflecting current evidence gaps. The panel emphasized benefits of LAIs in FEP and EP patients, with consensus that LAIs can decrease the risk of relapse, rehospitalization, and functional dysfunction. The panel supported links between these benefits and multidimensional longer-term functional recovery beyond symptomatic remission. Conclusions: Findings from this Delphi panel support the use of LAIs in FEP and EP schizophrenia patients regardless of disease severity, number of relapses, or social support status. Gaps in clinician knowledge make generating evidence on using LAIs in FEP and EP patients critical. [ABSTRACT FROM AUTHOR]

Background: Functional impairment affects many patients with schizophrenia. Treatment with the long-acting injectable antipsychotic aripiprazole once-monthly (AOM) may help improve functioning. Objectives: To explore changes in functioning in patients with schizophrenia who received AOM treatment in observational studies. Methods: Here we report functional outcomes in the form of Global Assessment of Functioning (GAF) scores in a pooled analysis of data from two observational studies from Canada (NCT02131415) and Germany (vfa non-interventional studies registry 15960N). Data from 396 patients were analyzed. Results: At baseline, the mean GAF score was 47.7 (SD 13.4). During 6 months of treatment with AOM, the mean GAF score increased to 59.4 (SD 15.8). Subgroups stratified by patient age (≤35 years/>35 years), sex, disease duration (≤5 years/>5 years) and disease severity at baseline had all significantly improved their GAF at month 6. 51.5% of the patients showed a GAF score increase of at least 10 points, which was regarded as clinically meaningful, and were considered responders. Conclusions: These data show that treatment with AOM may help improve patient functioning in a routine treatment setting. Trial registration: NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N. [ABSTRACT FROM AUTHOR]

Background: The therapeutic decision toward patients with schizophrenia is very different from one psychiatrist to another when faced with potentially similar clinical symptoms. It depends on many factors that are related to the patient's and the doctor's profiles, and the drug's characteristics. To date, no study has been conducted in Morocco on the prescribing habits of psychiatrists toward patients with schizophrenia. The objectives of our survey are to identify the molecules most prescribed by psychiatrists in Morocco for patients with schizophrenia and to determine the most common therapeutic strategies. Results: Our survey recruited 72 Moroccan psychiatrists. The median age was 36.5 years. 72.2% were women, and 37.5% had between 5 and 10 years of practice. More than two-thirds were practicing in the public sector in big cities. Olanzapine was an antipsychotic prescribed as first-line treatment for a patient with schizophrenia. For the majority, the most frequent combination was atypical antipsychotics with conventional neuroleptics. On the one hand, most psychiatrists reported prescribing neuroleptics long-acting injectable (neuroleptic LAIs). In the other hand, almost half of the participants had never prescribed second-generation antipsychotic long-acting injectables (SGA-LAIs). The high cost (77.8%), lack of availability of the product in certain sectors (33.3%), lack of therapeutic choice (26.4%), and lack of patient profile that could use the drug (23.6%), were among the strong reasons given for not prescribing SGA-LAIs. Conclusions: The treatment decision for patients with schizophrenia differs from one clinician to the other. It depends on various factors that may be related to the psychiatrist, the patient, and to the drug. [ABSTRACT FROM AUTHOR]

There is a growing number of protein drugs, yet their limited oral bioavailability requires that patients receive frequent, high dose injections. In situ forming implants (ISFIs) for controlled release of biotherapeutics have the potential to greatly reduce the injection frequency and improve patient compliance. However, protein release from ISFIs is a challenge due to their proclivity for instability. Specifically, factors such as the acidic microclimate within ISFIs can lead to protein aggregation and denaturation. Basic salts have been shown in PLGA microparticle and microcylinder formulations to significantly reduce protein instability by neutralizing this acidic environment. The overall objective of the study was to demonstrate that basic salts can be used with an ISFI system to neutralize the implant acidification. To this end, the basic salts MgCO3 and Mg(OH)2 were added to a protein-releasing ISFI and the effect on drug release, pH, implant swelling, implant diffusivity, and implant erosion were evaluated. Either salt added at 3 wt% neutralized the acidic environment surrounding the implants, keeping the pH at 6.64 ± 0.03 (MgCO3) and 6.46 ± 0.11 (Mg(OH)2) after 28 day compared to 3.72 ± 0.05 with no salts added. The salts initially increased solution uptake into the implants but delayed implant degradation and erosion. The 3 wt% Mg(OH)2 formulation also showed slightly improved drug release with a lower burst and increased slope. We showed that salt additives can be an effective way to modulate the pH in the ISFI environment, which can improve protein stability and ultimately improve the capacity of ISFIs for delivering pH-sensitive biomolecules. Such a platform represents a low-cost method of improving overall patient compliance and reducing the overall healthcare burden. [ABSTRACT FROM AUTHOR]

Introduction: Studies evaluating patient and healthcare professional (HCP) preferences regarding long-acting injectable (LAI) antipsychotic agent attributes are lacking. Methods: Surveys were administered to physicians, nurses, and patients who had at least two experiences with TV-46000, an investigational subcutaneous LAI antipsychotic agent for the treatment of schizophrenia, as part of the SHINE study (NCT03893825). Survey topics included preferences for route of administration, potential LAI dosing intervals (once-weekly, twice a month, once a month [q1m], every 2 months [q2m]), injection location, ease of use, syringe type, needle length, and need for reconstitution. Results: Patients (n = 63) had a mean (SD) age of 35.6 (9.6) years, age at diagnosis of 18 (10) years, and were mostly male (75%). There were 49 HCPs: 24 physicians and 25 nurses. Patients rated "a short needle" (68%), a "choice of [q1m or q2m] dosing interval" (59%), and "injection instead of oral tablet" (59%) as the most important features. HCPs rated "single injection to initiate treatment" (61%), "flexible dosing interval" (84%), and "injection instead of oral tablet" (59%) as the most important features. Subcutaneous injections were rated "easy to [receive/administer]" by 62% of patients and 84% of HCPs. When choosing between subcutaneous injections and intramuscular injections, 65% of HCPs preferred subcutaneous injections and 57% of patients preferred intramuscular injections. It was important to most HCPs to have four dose strength options (78%), a prefilled syringe (96%), and no need for reconstitution (90%). Conclusions: Patients had a range of responses, and on some issues patient and HCP preferences differed. Altogether, this suggests the importance of providing patients with a range of options and the importance of patient–HCP discussions on treatment preference for LAIs. Plain Language Summary: Several medications for treating schizophrenia are available as long-acting injections. One advantage of these medications is that patients do not need to take pills daily. In this study, patients, doctors, and nurses were asked what medication characteristics they preferred. Question topics were similar to the following: "how often should it be taken?"; "what method of delivery do you prefer?"; "where on the body should it be injected?"; "how easy was it to use?"; "what physical properties do you like?"; and "do preparation steps matter?" Patients thought that being able to be given monthly or every other month was one of the most important features of an injection (59%). Patients also liked a short needle (68%) and an injection instead of an oral pill (59%). Doctors and nurses responded that it was important to have a single injection to start treatment (61%). They also liked having options for how often the medication was given (84%), and an injection instead of an oral pill (59%). An injection was "easy to [get/give]" for most patients (62%) and doctors and nurses (84%). Most doctors and nurses (65%) liked giving injections under the skin. Most patients (57%) liked injections into the muscle. Overall, patients and doctors/nurses agreed on most topics. There were, however, a range of patient responses; therefore, it is important for patients and doctors and nurses to talk about the available treatment options. Each individual patient may have their own preferences. [ABSTRACT FROM AUTHOR]