Long-acting Treatment Research Articles

Biotechnologies and the future of opioid addiction treatments

The future of treatment—including addiction treatment—is biotechnological. Depot injections, agonist/antagonist implants, deep brain stimulation, and hapten conjugate vaccines are hailed by researchers and pharmaceutical manufacturers as medicine's best hope to minimize illicit use, to decrease risk of overdose and painful withdrawal, and to prevent diversion of medicines to illicit markets. Marketing and use of new technologies reveal old tensions framing concepts of addiction and its treatment: between medical condition and disorder of the will, between criminal justice and health, and between patient choice and system control. Using the examples of depot naltrexone and implantable and injectable buprenorphine in the U.S., this essay considers the arc of long-acting opioid treatment and implications for the future. These include the rise of Vivitrol courts and “carceral prescription”—where criminal justice systems mandate medicine to lock up brain receptors much as they might lock up people themselves—as well as use of buprenorphine formulations positioned as increasing both patient benefit and provider control. We also consider lessons from debates on long-acting contraceptive technologies such as Norplant and Depo-Provera. While multiple new long-acting formulations are under development, success will be determined less by characteristics of particular formulations and more by whether or not the new technologies are accompanied by a new ethics of addiction treatment that emphasizes therapeutic alliance, concordance over compliance, and a genuine commitment to allowing patients the ability to narrate and be believed in their descriptions of their treatment experiences.

P.494 Metabolic syndrome and QTc prolongation among patients receiving long-acting treatment: a comparative study between first and second-generation antipsychotics

P.494 Metabolic syndrome and QTc prolongation among patients receiving long-acting treatment: a comparative study between first and second-generation antipsychotics

Functional parameters of small airways can guide bronchodilator use in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) may present comorbid obstructive lung diseases with small airway dysfunction (SAD). Existing guidelines suggest that inhaled bronchodilators should be used if the ratio of forced expiratory volume in the 1st second and forced vital capacity (FEV1/FVC) < 0.7 in IPF. However, most IPF patients have FEV1/FVC > 0.7 even with coexisting emphysema. We retrospectively enrolled IPF patients who were registered at our outpatient clinic. At baseline, 63 patients completed computed tomography (CT) scans, lung function measurements, and symptom questionnaires. Among these patients, 54 (85.71%) underwent antifibrotic treatment and 38 (60.32%) underwent long-acting bronchodilator treatment. The median FEV1/FVC was 0.86. Not all patients treated with bronchodilators showed significant changes in lung function. IPF patients with SAD, determined by IOS parameters, showed significant improvement in FEV1, FEF25–75%, and symptom scores after bronchodilator treatment. Bronchodilator efficacy was not observed in patients without SAD. CT-confirmed emphysema was seen in 34.92% of patients. There were no changes in lung function or symptom scores after bronchodilator treatment in patients with emphysema. In conclusion, FEV1/FVC cannot reflect the airflow limitation in IPF. Emphysema in IPF is not a deciding factor in whether patients should receive bronchodilator treatment. IOS parameters may be useful to guide bronchodilator therapy in patients with IPF coexisting with SAD.

Impact of initiating long-acting injectable paliperidone palmitate on relapse and hospitalization in patients with bipolar I disorder: A mirror image retrospective study.

Literature assessing the use of long-acting injectable paliperidone palmitate in patients with bipolar I disorder is limited. The aim of this retrospective study was to determine the effectiveness of long-acting injectable paliperidone palmitate treatment on relapse and hospitalization in a real-world setting. Patients with bipolar I disorder aged 18-65 years, who were treated with paliperidone palmitate once-monthly (PP1M) for at least one year, were included. The rate of relapse, hospitalization, and length of hospital stay were collected. Safety outcomes included levels of prolactin, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein. The data of 36 patients who met the study criteria were evaluated. Number and length of hospitalizations, number of manic and mixed episodes significantly decreased after PP1M addition. When we compared the prolactin, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein levels as an indicator of the safety of treatment, there was no statistically significant change in these values before and after PP1M addition. Our findings suggested PP1M may be effective in reducing manic and mixed episodes. Limitations include a mirror image retrospective design and small sample size.

Management and Risk of Mortality in Patients Hospitalised Due to a First Severe COPD Exacerbation.

BackgroundReducing the need for hospitalisation in patients with chronic obstructive pulmonary disease (COPD) is an important goal in COPD management. The aim of this study was to evaluate re-hospitalisation, treatment, comorbidities and mortality in patients with COPD who were hospitalised for the first time due to a COPD exacerbation.MethodsThis was a retrospective, population-based observational cohort study of Swedish patients using linked data from three mandatory national health registries to assess re-hospitalisation rates, medication use and mortality. Rate of hospitalisation was calculated using the number of events divided by the number of person-years at risk; risk of all-cause and COPD-related mortality were assessed using Cox proportional hazard models.ResultsIn total, 51,247 patients were identified over 10 years; 35% of patients were not using inhaled corticosteroid, long-acting muscarinic antagonist or long-acting β2-agonist treatment prior to hospitalisation, 38% of whom continued without treatment after being discharged. Re-hospitalisation due to a second severe exacerbation occurred in 11.5%, 17.8% and 24% of the patients within 30, 90 and 365 days, respectively. Furthermore, 24% died during the first year following hospitalisation and risk of all-cause and COPD-related mortality increased with every subsequent re-hospitalisation. Comorbidities, including ischaemic heart disease, heart failure and pneumonia, were more common amongst patients who were re-hospitalised than those who were not.ConclusionFollowing hospitalisation for first severe COPD exacerbation, many patients did not collect the treatment recommended by current guidelines. Risk of mortality increased with every subsequent re-hospitalisation. Patients with concurrent comorbidities had an increased risk of being re-hospitalised.

DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas.

Drivers of sporadic benign pituitary adenoma growth are largely unknown. Whole-exome sequencing of 159 prospectively resected pituitary adenomas showed that somatic copy number alteration (SCNA) rather than mutation is a hallmark of hormone-secreting adenomas and that SCNAs correlate with adenoma phenotype. Using single-gene SCNA pathway analysis, we observed that both cAMP and Fanconi anemia DNA damage repair pathways were affected by SCNAs in growth hormone-secreting (GH-secreting) somatotroph adenomas. As somatotroph differentiation and GH secretion are dependent on cAMP activation and we previously showed DNA damage, aneuploidy, and senescence in somatotroph adenomas, we studied links between cAMP signaling and DNA damage. Stimulation of cAMP in C57BL/6 mouse primary pituitary cultures using forskolin or a long-acting GH-releasing hormone (GHRH) analog increased GH production and DNA damage measured by H2AX phosphorylation and a comet assay. Octreotide, a somatostatin receptor ligand that targets somatotroph adenoma GH secretion in patients with acromegaly, inhibited cAMP and GH and reversed DNA damage induction. In vivo long-acting GHRH treatment also induced pituitary DNA damage in mice. We conclude that cAMP, which induces somatotroph proliferation and GH secretion, may concomitantly induce DNA damage, potentially linking hormone hypersecretion to SCNA and genome instability. These results elucidating somatotroph adenoma pathophysiology identify pathways for targeted treatment.

Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment.

The leptin receptor-deficient db/db mouse model is an accepted in vivo model to study obesity, type 2 diabetes, and diabetic kidney disease. Healthy gastrointestinal (GI) microbiota has been linked to weight loss, improved glycemic control, and physiological benefits. We investigated the effect of various drugs on the GI microbiota of db/db mice as compared to control db/m mice. Treatment with long-acting pirfenidone (PFD) increased gut microbial diversity in diabetic db/db mice. Firmicutes, the most abundant phylum in db/m mice, decreased significantly in abundance in db/db mice but showed increased abundance with long-acting PFD treatment. Several bacterial taxa, including Lactobacillus and some Bacteroides, were less abundant in db/db mice and more abundant in long-acting-PFD-treated db/db mice. Long-acting PFD treatment reduced the abundance of Akkermansia muciniphila (5%) as compared to db/db mice (~15%). We conclude that gut microbial dysbiosis observed in db/db mice was partially reversed by long-acting PFD treatment and hypothesize that PFD has beneficial effects, in part, via its influence on the gut microbial metabolite profile. In quantitatively assessing urine metabolites, we observed a high abundance of diabetic ketoacidosis biomarkers, including 3-hydroxybutyric acid and acetoacetic acid in db/db mice, which were less abundant in the long-acting-PFD-treated db/db mice.

Production responses in adult ewes to long-acting anthelmintic treatment pre-mating: relationship with body condition score

ABSTRACT A trial was conducted to investigate the response of mixed age ewes of different body condition scores (BCS) to a pre-mating treatment with long-acting anthelmintics. Three hundred Poll–Dorset Texel cross ewes were divided into three groups of 100 and treated pre-mating with either a 100-day controlled-release capsule containing abamectin, albendazole, selenium and cobalt, a long-acting injectable formulation of moxidectin or remained untreated. Initially, ewes of lower BCS showed a significantly larger response in liveweight gain and a BCS increase which approached significance. However, these benefits did not persist following the expiry of the anthelmintics. Although treated ewes gave birth to more lambs, by weaning there was no significant difference between treatment groups in any of the measured variables and no significant influence of ewe BCS at treatment. The results are similar to earlier studies which showed that the benefits measured at the end of a long-acting anthelmintic treatment may not persist and may over-estimate the true benefit. Although there was a temporary benefit to treatment of low BCS ewes the data in general supports the view that many factors contribute to low BCS in ewes and parasites are often only a minor contributor.

Switching to Degludec is Associated with Reduced Hypoglycaemia, Irrespective of Definition Used or Patient Characteristics: Secondary Analysis of the ReFLeCT Prospective, Observational Study

IntroductionHypoglycaemia is a common side effect of insulin therapy; low or high glycated haemoglobin (HbA1c) levels, history of hypoglycaemia or long diabetes duration are known modifiers of hypoglycaemia risk. In randomised clinical trials, lower rates of hypoglycaemia have been observed with the new-generation insulin analogue, long-acting insulin degludec, compared with other basal insulins.MethodsThe ReFLeCT study was a prospective observational study over 12 months. Patient-reported diary data on hypoglycaemia were collected from patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) who were switching from other basal insulins to insulin degludec (degludec) at their physician’s discretion in routine clinical care. Two secondary analyses were undertaken to investigate the change in number of hypoglycaemic events: a post hoc analysis using the updated American Diabetes Association (ADA) level 1, 2 and 3 hypoglycaemia definitions, and a pre-specified analysis using patient characteristics (baseline HbA1c, diabetes duration, and physician’s rationale for initiating degludec).ResultsSwitching to degludec was associated with significantly fewer hypoglycaemic events for all definitions in T1D, and level 1 and 2 in T2D (too few level 3 events for statistical comparison). Moreover, patient characteristics did not influence the observed reduction in hypoglycaemia in T1D and T2D.ConclusionThese results demonstrate that switching to degludec from other basal insulins was associated with reduced rates of hypoglycaemia, irrespective of the definition used or baseline patient characteristics.Trial RegistrationNCT02392117Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-020-00875-1) contains supplementary material, which is available to authorized users.

Neuroprotective Activities of Long-Acting Granulocyte-Macrophage Colony-Stimulating Factor (mPDM608) in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Intoxicated Mice.

Loss of dopaminergic neurons along the nigrostriatal axis, neuroinflammation, and peripheral immune dysfunction are the pathobiological hallmarks of Parkinson's disease (PD). Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been successfully tested for PD treatment. GM-CSF is a known immune modulator that induces regulatory T cells (Tregs) and serves as a neuronal protectant in a broad range of neurodegenerative diseases. Due to its short half-life, limited biodistribution, and potential adverse effects, alternative long-acting treatment schemes are of immediate need. A long-acting mouse GM-CSF (mPDM608) was developed through Calibr, a Division of Scripps Research. Following mPDM608 treatment, complete hematologic and chemistry profiles and T-cell phenotypes and functions were determined. Neuroprotective and anti-inflammatory capacities of mPDM608 were assessed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice that included transcriptomic immune profiles. Treatment with a single dose of mPDM608 resulted in dose-dependent spleen and white blood cell increases with parallel enhancements in Treg numbers and immunosuppressive function. A shift in CD4+ T-cell gene expression towards an anti-inflammatory phenotype corresponded with decreased microgliosis and increased dopaminergic neuronal cell survival. mPDM608 elicited a neuroprotective peripheral immune transformation. The observed phenotypic shift and neuroprotective response was greater than observed with recombinant GM-CSF (rGM-CSF) suggesting human PDM608 as a candidate for PD treatment.

P-254 An experience of two Croatian centers in the treatment of gastroenteropancreatic neuroendocrine neoplasms with long-acting octreotide treatment

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors whose incidence has increased steadily over the past decades. Octreotide is a somatostatin analogue which has traditionally been used for the relief of symptoms that result from the release of peptides and amines (carcinoid syndrome), although a substantial amount of evidence suggests that it has anti-proliferative effects and lengthens the time to progression of the disease. We’ve aimed to evaluate the relationship between octreotide use and progression-free survival (PFS) and overall survival (OS). Medical records of 76 patients with gastroenteropancreatic NENs treated with long-acting octreotide in the University Hospital Centre Zagreb and University Hospital Center Sisters of Charity were collected in the period from March 2011 to March 2019. A retrospective analysis was completed with the Kaplan-Meier method using the PFS and OS as a primary endpoint. Previous to octreotide treatment patients had confirmed high expression of somatostatin receptors (sst-rs) by tetroktyde scintigraphy. All patients were followed for a median of 38 months, all of them where grade 1 (27%) or grade 2 (73%). Median PFS for all patients was estimated at 12 ± 2,5 months (95% CI 9,62-14,38). Median PFS for patients with pancreatic NETs was estimated at 10 ± 0,5 months (95% CI 7,03-12,97; median Ki-67 10%), patients with NET of large intestine at 10 ± 3,67 months (95% CI 2,87-17,13; median Ki-67 14%), patients with NETs of unknown primary at 12 ± 2,6 months (95% CI 4,93-19,07; median Ki-67 6%) and for patients with NETs of small intestine at 30 ± 14,5 months (95% CI 1,57-58,48; median Ki-67 5%). Median OS was not reached in any subgroup of patients. Although overall median PFS is lower than in the PROMID study, the fact that the median OS was not reached renders long-acting octreotide as an effective treatment option with acceptable tolerability. This patient population was more heterogenous than in clinical trials and reflects the real-life setting of clinical practice.

Patient-Reported Outcomes in ATLAS and FLAIR Participants on Long-Acting Regimens of Cabotegravir and Rilpivirine Over 48 Weeks

The phase 3 ATLAS and FLAIR studies demonstrated that maintenance with Long-Acting (LA) intramuscular cabotegravir and rilpivirine is non-inferior in efficacy to current antiretroviral (CAR) oral therapy. Both studies utilized Patient-Reported Outcome instruments to measure treatment satisfaction (HIVTSQ) and acceptance (ACCEPT general domain), health status (SF-12), injection tolerability/acceptance (PIN), and treatment preference. In pooled analyses, LA-treated patients (n = 591) demonstrated greater mean improvements from baseline than the CAR group (n = 591) in treatment satisfaction (Week 44, + 3.9 vs. +0.5 HIVTSQs-points; p < 0.001) and acceptance (Week 48, +8.8 vs. +2.0 ACCEPT-points; p < 0.001). The acceptability of injection site reactions (PIN) significantly improved from week 5 (2.10 points) to week 48 (1.62 points; p < 0.001). In both studies, ≥ 97% of LA group participants with recorded data preferred LA treatment compared with prior oral therapy. These results further support the potential of a monthly injectable option for people living with HIV seeking an alternative to daily oral treatment.

MON-301 Long-Acting SSA Treatment Patterns in Sweden From 2005 to 2017: A Nationwide Study

BackgroundAcromegaly is a complex disease, primarily treated with pituitary surgery or long-acting somatostatin analogues (LA-SSA). Few studies have examined real-world use of LA-SSA. This analysis evaluated LA-SSA treatment patterns in Sweden for patients with acromegaly.MethodsData were obtained from nationwide health care registers. Patients were included if they had diagnosis codes for acromegaly and neoplasm of the pituitary gland between Jul 1, 2005 and Dec 31, 2017, and at least one purchase of LA-SSA (lanreotide [LAN] 60, 90, or 120 mg, or octreotide [OCT] 10, 20, or 30 mg). Cox regression models were used for analyses of persistence and switching.ResultsThe analysis included 176 pts treated with LA-SSA in 2005-2017. The cohort was subgrouped on year of initiation of LA-SSA (2005-2011, n=90, 51%; 2012-2017, n=86, 49%). In the first period, 36 pts (40%) initiated LAN while 54 pts (60%) initiated OCT while in the later period, 44 pts (51%) initiated LAN and 42 pts (49%) initiated OCT (p=0.17). No patients initiated pasireotide. Patient characteristics were similar between LAN and OCT initiators, but history of pituitary surgery was more common for LAN as compared to OCT (LAN 62%; OCT 46%, p<0.05). Similar results were seen for visual-field defects (LAN 20%, OCT 8%, p<0.05). Median (95%CI) follow-up was not significantly different [LAN 5.3 (3.7; 6.0) yrs.; OCT 6.4 (4.5; 7.6)].The mean (95%CI) dose interval was not significantly different, 30.5 (28.7; 32.6) days for LAN vs 29.5 (28.5; 30.3) days for OCT. The median (95%CI) duration of 1st-line LA-SSA treatment was 14.4 (10.8; 21.6) months for LAN and 12.0 (7.2; 19.2) months for OCT. Fifty-one pts (64%) discontinued 1st-line LAN while 70 pts (73%) discontinued 1st-line OCT (hazard ratio (HR) LAN vs. OCT 0.80; 95% CI: 0.56-1.15). Due to the use of register data, the reason for therapy change could not be determined. Eight pts (10%) switched LAN to OCT while 29 pts (30%) switched OCT to LAN. Patients initiated on OCT were more likely to switch to LAN than the other way around (HR for switch for 1st-line LAN vs. OCT 0.33; 95% CI 0.15-0.72). Among patients who switched OCT to LAN, 67% of LAN dispensing was 120 mg, 21% 90 mg, and 12% 60 mg. Among patients who switch LAN to OCT, 84% of OCT dispensing was 30 mg, and 16% 20 mg.ConclusionsThere was no significant difference in the number of patients initiated on LAN or OCT despite the later introduction of LAN in Sweden. Patient characteristics were similar but LAN initiators were more likely to have undergone surgery and be diagnosed with visual field defects which could indicate that physicians initiate LAN in patients with more aggressive disease. Extended dose intervals with LAN (dosing every 6-8 w) do not seem to be commonly used in Sweden. In comparison to OCT, patients initiated on LAN were significantly less likely to change LA-SSA therapy.

Effects of acute and repeated treatment with methocinnamox, a mu opioid receptor antagonist, on fentanyl self-administration in rhesus monkeys.

Methocinnamox (MCAM), a mu opioid receptor antagonist with a long duration of action, attenuates heroin self-administration in rhesus monkeys, suggesting it could be an effective treatment for opioid use disorder (OUD). This study examined effects of acute and repeated MCAM administration on self-administration of the high-efficacy mu opioid receptor agonist fentanyl and characterized MCAM pharmacokinetics. Four rhesus monkeys self-administered i.v. infusions of fentanyl (0.00032 mg/kg/infusion) or cocaine (0.032 mg/kg/infusion). MCAM (0.1-0.32 mg/kg) or the opioid receptor antagonist naltrexone (0.001-0.032 mg/kg) was injected prior to test sessions to evaluate acute effects. On a separate occasion, 0.32 mg/kg MCAM was injected every 12 days for 5 total injections to evaluate the effectiveness of repeated treatment. Following acute injection, MCAM and naltrexone decreased fentanyl self-administration on the day of treatment, with attenuation lasting for up to 2 weeks after the larger MCAM dose and <1 day after naltrexone. Repeated MCAM administration decreased fentanyl self-administration for more than 2 months without altering cocaine self-administration. MCAM plasma concentrations peaked 15-45 min after injection, with a half-life ranging from 13.7 to 199.8 min, and decreased markedly 1 day after injection. MCAM selectively reduced opioid self-administration and remained effective with repeated administration. Moreover, MCAM was effective at times when plasma levels were very low, suggesting that pharmacodynamic (i.e., pseudoirreversible binding to mu opioid receptors) and not pharmacokinetic factors play a significant role in its long-lasting effects. Taken together with previous studies, these data indicate that MCAM could be a safe, effective, and long-acting treatment for OUD.

A single assessment with the Brief Adherence Rating Scale (BARS) discriminates responders to long-acting injectable antipsychotic treatment in patients with schizophrenia

ObjectiveTo determine if a single baseline adherence assessment (Brief Adherence Rating Scale [BARS]) could identify patients who are likely to respond to long-acting injectable (LAI) antipsychotic treatment. MethodThe current secondary analysis included a sub-sample of adult outpatients (N = 176) with schizophrenia or schizoaffective disorder who participated in the “A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS)” trial and had a baseline BARS assessment and a baseline and month 3 Positive and Negative Syndrome Scale (PANSS) rating. The main outcome was LAI treatment response, defined as a ≥ 20% decrease (baseline to month 3) on the PANSS total score. Receiver Operating Characteristic (ROC) and Area Under the Curve (AUC) analysis was conducted to determine the optimal cutpoint of baseline BARS adherence in discriminating LAI treatment response at month 3. A logistic mixed model estimated the odds of response to LAI treatment at month 3 from the optimal baseline BARS cutpoint. ResultsThe ROC analysis determined that the single baseline BARS rating (cutoff ≤66%), indicating low adherence, best discriminated patients likely to respond to LAI treatment (AUC = 0.603, SE = 0.046, 95% binomial exact CI = 0.527 to 0.676, p = 0.025), with 38% sensitivity and 85% specificity. The logistic mixed model analysis revealed that patients with ≤66% BARS adherence had 3.464 times the predicted odds (95% CI = 1.604 to 7.480, p = 0.001) of responding to LAI treatment than those who were >66% BARS adherent. ConclusionA single baseline BARS assessment discriminated response to LAI treatment suggesting it is a reasonable tool to identify candidates for LAI antipsychotic treatment.

Successful Long-Acting Paliperidone Treatment Following Reversible Risperidone-Induced Neutropenia.

Successful Long-Acting Paliperidone Treatment Following Reversible Risperidone-Induced Neutropenia.

Prevalence and correlates of food insecurity in community-based individuals with severe mental illness receiving long-acting injectable antipsychotic treatment.

People with severe mental illness (SMI) have numerous risk factors that may predispose them to food insecurity (FI); however, the prevalence of FI and its effects on health are under-researched in this population. The present study aimed to describe the prevalence of FI and its relationship to lifestyle factors in people with SMI. This cross-sectional study recruited people with SMI receiving long-acting injectable (LAI) antipsychotic medication from community services at three sites in Sydney, Australia. Assessments were completed on physical health and lifestyle factors. χ2 Tests, independent-samples t tests and binary logistic regression analyses were calculated to examine relationships between lifestyle factors and FI. In total, 233 people completed the assessments: 154 were males (66 %), mean age 44·8 (sd 12·7) years, and the majority (70 %) had a diagnosis of schizophrenia. FI was present in 104 participants (45 %). People with FI were less likely to consume fruits (OR 0·42, 95 % CI 0·24, 0·74, P = 0·003), vegetables (OR 0·39, 95 % CI 0·22, 0·69, P = 0·001) and protein-based foods (OR 0·45, 95 % CI 0·25, 0·83, P = 0·011) at least once daily, engaged in less moderate to vigorous physical activity (min) (OR 0·997, 95 % CI 0·993, 1·000, P = 0·044), and were more likely to smoke (OR 1·89, 95 % CI 1·08, 3·32, P = 0·026). FI is highly prevalent among people with SMI receiving LAI antipsychotic medications. Food-insecure people with SMI engage in less healthy lifestyle behaviours, increasing the risk of future non-communicable disease.

Perspectives of injectable long acting antiretroviral therapies for HIV treatment or prevention: understanding potential users’ ambivalences

ABSTRACTRecent clinical trial data showed that injectable long-acting antiretroviral treatment (LA-ART) every four or eight weeks could become an alternative option for HIV treatment or prevention. The purpose of our study was to explore perceptions and potential users’ points of views of this new mode of administration through individuals’ therapeutic itinerary and their singular history with ART. Between 2018 and 2019, a qualitative study was conducted in two University Hospitals in Paris, France. In-depth interviews were conducted with 15 virologically controlled People Living with HIV (PLWH) and 13 men on pre-exposure prophylaxis (PrEP) for at least six months. Interviews, focused on the daily experience with ART, were recorded, transcribed, and analyzed using thematic content analysis. Collected discourses were organized around three emergent concerns: social, material and experimental. Each of these concerns was perceived as ambivalent, balanced by skepticism and hope. It revealed the complexity of each individual's relationship to their HIV treatment or PrEP, leading to balance the injectable LA-ART popularity reported within clinical trials. This new mode of administration may be a suitable alternative for some PLWH and PrEP users, a “simplification” compared to the oral route. It opens a window for “customizable” ART-treatment according to individuals’ lives.

Recovery From Opioid Use Disorder (OUD) After Monthly Long-acting Buprenorphine Treatment: 12-Month Longitudinal Outcomes From RECOVER, an Observational Study.

Objectives:While evidence has mounted regarding the short-term effectiveness of pharmacotherapy for opioid use disorder (OUD), little is known about longer-term psychosocial, economic, and health outcomes. We report herein 12-month outcomes for an observational study enrolling participants who had previously taken part in a long-acting buprenorphine subcutaneous injection (BUP-XR) trial for moderate to severe OUD.Methods:The RECOVER (Remission from Chronic Opioid Use: Studying Environmental and SocioEconomic Factors on Recovery; NCT03604861) study enrolled participants from 35 US community-based sites. Self-reported sustained opioid abstinence over 12 months and self-reported past-week abstinence at 3-, 6-, 9-, and 12-month visits were assessed. Multiple regression models assessed the association of BUP-XR duration with abstinence, controlling for potential confounders. Withdrawal, pain, health-related quality of life, depression, and employment at RECOVER baseline and 12-month visits were also compared to values collected before treatment in the BUP-XR trial.Results:Of 533 RECOVER participants, 425 completed the 12-month visit (average age 42 years; 66% male); 50.8% self-reported sustained 12-month and 68.0% past-week opioid abstinence. In multiple regressions, participants receiving 12-month versus ≤2-month BUP-XR treatment duration had significantly higher likelihood of sustained opioid abstinence (75.3% vs 24.1%; P = 0.001), with similar results for past-week self-reported abstinence over time. During RECOVER, participants had fewer withdrawal symptoms, lower pain, positive health-related quality of life, minimal depression, and higher employment versus pre-trial visit.Conclusions:RECOVER participants reported positive outcomes over the 12-month observational period, including high opioid abstinence and stable or improved humanistic outcomes. These findings provide insights into the long-term impact of pharmacotherapy in OUD recovery.

Natural plant-derived polygalacturonic acid-oleanolic acid assemblies as oral-delivered nanomedicine for insulin resistance treatment

Exogenous insulin administration is still the most used treatment for diabetes (mainly used for type-1 diabetes in clinic), however type 2 diabetes (T2D) with the characteristics of insulin resistance accounts for the vast majority proportion (90–95%) of diabetic population, which makes insulin function failure. Currently, many efforts have been devoted to insulin delivery with nanomedicine means, whereas the treatment of insulin resistance in T2D using nanotechnology strategy is rarely reported. In this study, we transformed a plant-derived natural insulin sensitizer into biocompatible nano-transport system, where the natural insulin sensitizer oleanolic acid (OA) was conjugated onto natural polymer polygalacturonic acid (PGA) to form self-assembled micelles as oral administrated nanomedcine for insulin resistance treatment in T2D. In vitro and in vivo investigation demonstrated that OA loaded PGA-OA micelles possess stability to cross the gastrointestinal barriers and improve drug intestinal absorption, remarkably maintaining plasma drug concentration for a longer time. Therefore, this formulation manifested good reversal effect on insulin resistance in the T2D rat model, and thereby exhibited long-term outcomes in glucose level control even after drug withdrawal. Additionally, the molecular mechanism of OA loaded PGA-OA mediated insulin-resistant reversal was found that it was probable mediated by promoting IRS-1/PI3K/AKT signaling pathway and inhibiting the activity of PTP1B enzyme simultaneously. In this regard, such a facile, safe and potent nanomedicine strategy may be promising alternative for long-acting insulin-resistant treatment in T2D therapy.