In cryptogenic stroke and atrial cardiopathy, apixaban did not reduce recurrent stroke vs. aspirin.

SOURCE CITATION: Kamel H, Longstreth WT Jr, Tirschwell DL, et al; ARCADIA Investigators. Apixaban to prevent recurrence after cryptogenic stroke in patients with atrial cardiopathy: the ARCADIA randomized clinical trial. JAMA. 2024;331:573-581. 38324415.

In subclinical AF, apixaban reduced stroke or systemic embolism but increased major bleeding vs. aspirin at 3.5 y.

SOURCE CITATION: Healey JS, Lopes RD, Granger CB, et al; ARTESIA Investigators. Apixaban for stroke prevention in subclinical atrial fibrillation. N Engl J Med. 2024;390:107-117. 37952132.

Associations of Apixaban Dose With Safety and Effectiveness Outcomes in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease.

BACKGROUND: Recommendations for apixaban dosing on the basis of kidney function are inconsistent between the US Food and Drug Administration and European Medicines Agency for patients with atrial fibrillation. Optimal apixaban dosing in chronic kidney disease remains unknown. METHODS: With the use of deidentified electronic health record data from the Optum Labs Data Warehouse, patients with atrial fibrillation and chronic kidney disease stage 4/5 initiating apixaban between 2013 and 2021 were identified. Risks of bleeding and stroke/systemic embolism were compared by apixaban dose (5 versus 2.5 mg), adjusted for baseline characteristics by the inverse probability of treatment weighting. The Fine-Gray subdistribution hazard model was used to account for the competing risk of death. Cox regression was used to examine risk of death by apixaban dose. RESULTS: Among 4313 apixaban new users, 1705 (40%) received 5 mg and 2608 (60%) received 2.5 mg. Patients treated with 5 mg apixaban were younger (mean age, 72 versus 80 years), with greater weight (95 versus 80 kg) and higher serum creatinine (2.7 versus 2.5 mg/dL). Mean estimated glomerular filtration rate was not different between the groups (24 versus 24 mL·min-1·1.73 m-2). In inverse probability of treatment weighting analysis, apixaban 5 mg was associated with a higher risk of bleeding (incidence rate 4.9 versus 2.9 events per 100 person-years; incidence rate difference, 2.0 [95% CI, 0.6-3.4] events per 100 person-years; subdistribution hazard ratio, 1.63 [95% CI, 1.04-2.54]). There was no difference between apixaban 5 mg and 2.5 mg groups in the risk of stroke/systemic embolism (3.3 versus 3.0 events per 100 person-years; incidence rate difference, 0.2 [95% CI, -1.0 to 1.4] events per 100 person-years; subdistribution hazard ratio, 1.01 [95% CI, 0.59-1.73]), or death (9.9 versus 9.4 events per 100 person-years; incidence rate difference, 0.5 [95% CI, -1.6 to 2.6] events per 100 person-years; hazard ratio, 1.03 [95% CI, 0.77-1.38]). CONCLUSIONS: Compared with 2.5 mg, use of 5 mg apixaban was associated with a higher risk of bleeding in patients with atrial fibrillation and severe chronic kidney disease, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing recommendations on the basis of kidney function by the European Medicines Agency, which differ from those issued by the US Food and Drug Administration.

HIV preexposure prophylaxis in adolescents and young adults: an update.

PURPOSE OF REVIEW: This review provides an update of evidence for HIV preexposure prophylaxis (PrEP), including efficacy and safety of newly available medications. It discusses barriers to care that are unique to adolescents and young adults as well as interventions that may help increase uptake, adherence, and retention in care. RECENT FINDINGS: Tenofovir alafenamide-emtricitabine and cabotegravir are both newly approved medications for the prevention of HIV and are well tolerated and effective for adolescents. These medications, along with tenofovir disoproxil-emtricitabine, offer a variety of PrEP options to choose from. SUMMARY: Adolescents and young adults have many options when it comes to HIV prevention, but barriers persist in terms of uptake and adherence to PrEP and retention in care. Technology-based interventions, provider education, navigation support, and multiple access options are all tools to help increase PrEP use in young people.

Avoiding Shots in the Dark: Learning from the Past To Inform the Implementation of Long-Acting Injectable Pre-Exposure Prophylaxis for Black American Cisgender Women.

The FDA's approval of long-acting injectable cabotegravir pre-exposure prophylaxis (LAI PrEP) as an alternative to daily oral PrEP represents a crucial development in HIV prevention, particularly for American Black cisgender women who face high HIV-1 risks. Yet, uptake may be hindered by racial and gender inequities. Addressing these requires learning from the roll-out of oral PrEP, creating culturally tailored PrEP campaigns, and enhancing provider training to meet Black women's needs. Tools for discussing PrEP within personal relationships and product preference research tailored to Black women's needs are essential for effective LAI PrEP delivery. Deliberative implementation of LAI PrEP must employ strategies that are community-sensitive, -responsive, and -inclusive. It should prioritize the incorporation of Black women's voices in decision-making and should promote community-led strategies. By addressing historical injustices and fostering trust, healthcare systems can enhance LAI PrEP uptake by Black women. Emphasizing a community-centered approach that ensures health equity and acknowledges the crucial role that social media and Black-led organizations play in promoting PrEP awareness and adoption within Black communities is necessary for successful implementation.

High Propensity to Switch to Long-acting Injectable HIV PrEP with Cabotegravir in a Cohort of Oral PrEP Experienced Men who Have Sex with Men in Italy.

Aim was to investigate the propensity to switch to long-acting injectable HIV pre-exposure prophylaxis (PrEP) with cabotegravir among oral PrEP-experienced men who have sex with men. Out of 377 PrEP users, 325 (86.2%) were interested (would like = 210) or considering (would consider = 115) switch to long-acting PrEP. At multivariable analysis, the odds ratio of interest in long-acting PrEP in non-adherent vs. adherent individuals to oral PrEP was 5.03 (95%CI = 1.73-14.61,p = 0.003) and of consideration 1.63 (95%CI = 0.51-5.23,p = 0.410). We observed very high propensity to switch to long-acting PrEP, particularly among non-adherent users. Rapid availability of long-acting PrEP might address unmet needs of PrEP users in Italy.

Improving preparedness for introducing and scaling up long-acting HIV pre-exposure prophylaxis in Asia.

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.

Multitasking Pharmacophores Support Cabotegravir-Based Long-Acting HIV Pre-Exposure Prophylaxis (PrEP).

Cabotegravir is an integrase strand transfer inhibitor (INSTI) for HIV treatment and prevention. Cabotegravir-based long-acting pre-exposure prophylaxis (PrEP) presents an emerging paradigm for infectious disease control. In this scheme, a combination of a high efficacy and low solubility of anti-infection drugs permits the establishment of a pharmaceutical firewall in HIV-vulnerable groups over a long period. Although the structure-activity-relationship (SAR) of cabotegravir as an INSTI is known, the structural determinants of its low solubility have not been identified. In this work, we have integrated multiple experimental and computational methods, namely X-ray diffraction, solid-state NMR (SSNMR) spectroscopy, solution NMR spectroscopy, automated fragmentation (AF)-QM/MM and density functional theory (DFT) calculations, to address this question. The molecular organization of cabotegravir in crystal lattice has been determined. The combination of very-fast magic-angle-sample-spinning (VF MAS) SSNMR and solution NMR, as supported by AF-QM/MM and DFT calculations, permits the identification of structural factors that contribute to the low aqueous solubility of cabotegravir. Our study reveals the multitasking nature of pharmacophores in cabotegravir, which controls the drug solubility and, meanwhile, the biological activity. By unraveling these function-defining molecular features, our work could inspire further development of long-acting HIV PrEP drugs.

Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial.

BACKGROUND: Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women. METHODS: HPTN 084 was a phase 3, randomised, double-blind, double-dummy, active-controlled, superiority trial in 20 clinical research sites in seven countries in sub-Saharan Africa. Participants were eligible for enrolment if they were assigned female sex at birth, were aged 18-45 years, reported at least two episodes of vaginal intercourse in the previous 30 days, were at risk of HIV infection based on an HIV risk score, and agreed to use a long-acting reversible contraceptive method. Participants were randomly assigned (1:1) to either active cabotegravir with TDF-FTC placebo (cabotegravir group) or active TDF-FTC with cabotegravir placebo (TDF-FTC group). Study staff and participants were masked to study group allocation, with the exception of the site pharmacist who was responsible for study product preparation. Participants were prescribed 5 weeks of daily oral product followed by intramuscular injections every 8 weeks after an initial 4-week interval load, alongside daily oral pills. Participants who discontinued injections were offered open-label daily TDF-FTC for 48 weeks. The primary endpoints of the study were incident HIV infection in the intention-to-treat population, and clinical and laboratory events that were grade 2 or higher in all women who had received at least one dose of study product. This study is registered with ClinicalTrials.gov, NCT03164564. FINDINGS: From Nov 27, 2017, to Nov 4, 2020, we enrolled 3224 participants (1614 in the cabotegravir group and 1610 in the TDF-FTC group). Median age was 25 years (IQR 22-30); 1755 (54·7%) of 3209 had two or more partners in the preceding month. 40 incident infections were observed over 3898 person-years (HIV incidence 1·0% [95% CI 0·73-1·40]); four in the cabotegravir group (HIV incidence 0·2 cases per 100 person-years [0·06-0·52]) and 36 in the TDF-FTC group (1·85 cases per 100 person-years [1·3-2·57]; hazard ratio 0·12 [0·05-0·31]; p<0·0001; risk difference -1·6% [-1·0% to -2·3%]. In a random subset of 405 TDF-FTC participants, 812 (42·1%) of 1929 plasma samples had tenofovir concentrations consistent with daily use. Injection coverage was 93% of the total number of person-years. Adverse event rates were similar across both groups, apart from injection site reactions, which were more frequent in the cabotegravir group than in the TDF-FTC group (577 [38·0%] of 1519 vs 162 [10·7%] of 1516]) but did not result in injection discontinuation. Confirmed pregnancy incidence was 1·3 per 100 person-years (0·9-1·7); no congenital birth anomalies were reported. INTERPRETATION: Although both products for HIV prevention were generally safe, well tolerated, and effective, cabotegravir was superior to TDF-FTC in preventing HIV infection in women. FUNDING: National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and the Bill & Melinda Gates Foundation. Additional support was provided through the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ViiV Healthcare and Gilead Sciences provided pharmaceutical support.

Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial.

INTRODUCTION: Oral pirfenidone reduces lung function decline and mortality in patients with idiopathic pulmonary fibrosis (IPF). Systemic exposure can have significant side effects, including nausea, rash, photosensitivity, weight loss and fatigue. Reduced doses may be suboptimal in slowing disease progression. METHODS: This phase 1b, randomised, open-label, dose-response trial at 25 sites in six countries (Australian New Zealand Clinical Trials Registry (ANZCTR) registration number ACTRN12618001838202) assessed safety, tolerability and efficacy of inhaled pirfenidone (AP01) in IPF. Patients diagnosed within 5 years, with forced vital capacity (FVC) 40%-90% predicted, and intolerant, unwilling or ineligible for oral pirfenidone or nintedanib were randomly assigned 1:1 to nebulised AP01 50 mg once per day or 100 mg two times per day for up to 72 weeks. RESULTS: We present results for week 24, the primary endpoint and week 48 for comparability with published trials of antifibrotics. Week 72 data will be reported as a separate analysis pooled with the ongoing open-label extension study. Ninety-one patients (50 mg once per day: n=46, 100 mg two times per day: n=45) were enrolled from May 2019 to April 2020. The most common treatment-related adverse events (frequency, % of patients) were all mild or moderate and included cough (14, 15.4%), rash (11, 12.1%), nausea (8, 8.8%), throat irritation (5, 5.5%), fatigue (4, 4.4%) and taste disorder, dizziness and dyspnoea (three each, 3.3%). Changes in FVC % predicted over 24 and 48 weeks, respectively, were -2.5 (95% CI -5.3 to 0.4, -88 mL) and -4.9 (-7.5 to -2.3,-188 mL) in the 50 mg once per day and 0.6 (-2.2 to 3.4, 10 mL) and -0.4 (-3.2 to 2.3, -34 mL) in the 100 mg two times per day group. DISCUSSION: Side effects commonly associated with oral pirfenidone in other clinical trials were less frequent with AP01. Mean FVC % predicted remained stable in the 100 mg two times per day group. Further study of AP01 is warranted. TRIAL REGISTRATION NUMBER: ACTRN12618001838202 Australian New Zealand Clinical Trials Registry.

Identifying treatment heterogeneity in atrial fibrillation using a novel causal machine learning method.

BACKGROUND: Lifelong oral anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent stroke. Over the last decade, multiple new oral anticoagulants (OACs) have expanded the number of treatment options for these patients. While population-level effectiveness of OACs has been compared, it is unclear if there is variability in benefit and risk across patient subgroups. METHODS: We analyzed claims and medical data for 34,569 patients who initiated a nonvitamin K antagonist oral anticoagulant (non-vitamin K antagonist oral anticoagulant (NOAC); apixaban, dabigatran, and rivaroxaban) or warfarin for nonvalvular AF between 08/01/2010 and 11/29/2017 from the OptumLabs Data Warehouse. A machine learning (ML) method was applied to match different OAC groups on several baseline variables including, age, sex, race, renal function, and CHA2DS2 -VASC score. A causal ML method was then used to discover patient subgroups characterizing the head-to-head treatment effects of the OACs on a primary composite outcome of ischemic stroke, intracranial hemorrhage, and all-cause mortality. RESULTS: The mean age, number of females and white race in the entire cohort of 34,569 patients were 71.2 (SD, 10.7) years, 14,916 (43.1%), and 25,051 (72.5%) respectively. During a mean follow-up of 8.3 (SD, 9.0) months, 2,110 (6.1%) of patients experienced the composite outcome, of whom 1,675 (4.8%) died. The causal ML method identified 5 subgroups with variables favoring apixaban over dabigatran; 2 subgroups favoring apixaban over rivaroxaban; 1 subgroup favoring dabigatran over rivaroxaban; and 1 subgroup favoring rivaroxaban over dabigatran in terms of risk reduction of the primary endpoint. No subgroup favored warfarin and most dabigatran vs warfarin users favored neither drug. The variables that most influenced favoring one subgroup over another included Age, history of ischemic stroke, thromboembolism, estimated glomerular filtration rate, Race, and myocardial infarction. CONCLUSIONS: Among patients with AF treated with a NOAC or warfarin, a causal ML method identified patient subgroups with differences in outcomes associated with OAC use. The findings suggest that the effects of OACs are heterogeneous across subgroups of AF patients, which could help personalize the choice of OAC. Future prospective studies are needed to better understand the clinical impact of the subgroups with respect to OAC selection.

Pharmacology of boosted and unboosted integrase strand transfer inhibitors for two-dose event-driven HIV prevention regimens among men.

BACKGROUND: Event-driven HIV prevention strategies are a priority for users who do not require daily pre-exposure prophylaxis (PrEP). Regimens containing integrase strand transfer inhibitors (INSTIs) are under evaluation as alternatives to daily PrEP. To better understand INSTI distribution and inform dosing selection we compared the pharmacology of two-dose boosted elvitegravir and unboosted bictegravir regimens in MSM. MATERIALS AND METHODS: Blood, rectal and penile secretions and rectal biopsies were collected from 63 HIV-negative MSM aged 18-49 years. Specimens were collected up to 96 h after two oral doses of tenofovir alafenamide and emtricitabine with elvitegravir boosted by cobicistat or unboosted bictegravir given 24 h apart. Antiretroviral drugs were measured by LC-MS. RESULTS: Mean bictegravir plasma concentrations remained above the 95% protein-adjusted effective concentration 96 h after dosing [273 (95% CI: 164-456) ng/mL] whereas elvitegravir plasma concentrations became undetectable 48 h after the second dose. Bictegravir and elvitegravir reached rectal tissues within 2 h after the first dose, and elvitegravir tissue concentrations [1.07 (0.38-13.51) ng/mg] were greater than bictegravir concentrations [0.27 (0.15-0.70) ng/mg]. Both INSTIs became undetectable in tissues within 96 h. Elvitegravir and bictegravir were not consistently detected in penile secretions. CONCLUSIONS: Whereas bictegravir plasma concentrations persist at least 4 days after a two-oral-dose HIV prophylaxis regimen, elvitegravir accumulates in mucosal tissues. Differing elvitegravir and bictegravir distribution may result in variable mucosal and systemic antiviral activity and can inform dosing strategies for event-driven HIV prevention.

Long-acting injectable cabotegravir for PrEP: A game-changer in HIV prevention?

BACKGROUND: Long-acting injectable cabotegravir (CAB-LA) represents a new additional option for HIV prevention in people at substantial risk of HIV infection that may fill the gaps in pre-exposure prophylaxis (PrEP) uptake, adherence, and retention in users having difficulty with oral PrEP. Data from clinical trials demonstrated that CAB-LA was safe, highly effective, and well-accepted for HIV prevention. However, the occurrence of breakthrough HIV infections despite timely injections, HIV seroconversion timing and patterns, risk of selection and dissemination of resistance-associated mutations to integrase inhibitors, complexity of follow-up, logistical considerations, and its cost effectiveness compared with oral PrEP constitute significant issues for the integration of CAB-LA into clinical routine. FINDINGS: These concerns need to be addressed before moving forward with large-scale implementation programmes. Pilot and implementation projects are required in the following areas: HIV testing algorithms, patient education, clinic procedures, protocols for switching and discontinuation, efficacy and safety in populations not included in clinical trials, and demedicalization processes. The development of models to increase the uptake of, adherence to, and persistence with and after CAB-LA injections will also be of paramount importance for success. Lessons learned from these projects will increase experience, staff expertise, and organizational and training capacities to support the roll-out of this new agent as part of HIV prevention programmes. CONCLUSION: CAB-LA has not yet achieved its full potential in HIV prevention, and strong commitment from all stakeholders is required to push CAB-LA as a game-changer in HIV response.

Verbal fluency functional magnetic resonance imaging detects anti-seizure effects and affective side effects of perampanel in people with focal epilepsy.

Perampanel, a noncompetitive antagonist of the postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic-clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping-derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency functional magnetic resonance imaging (fMRI) twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in anti-seizure medication (ASM) regimen in-between. After commencing perampanel, individuals had higher task-related activations in left orbitofrontal cortex (OFC), fewer task-related activations in the subcortical regions including the left thalamus and left caudate, and lower task-related thalamocaudate and caudate-subtantial nigra connectivity. Decreased task-related connectivity is observed between the left OFC and precuneus and left medial frontal lobe. Our results highlight the brain regions associated with the beneficiary therapeutic effects on focal to bilateral tonic-clonic seizures (thalamus and caudate) but also the undesired affective side effects of perampanel with increased anger and aggression (OFC).

Clinical comprehensive evaluation of direct oral anticoagulants for patients with atrial fibrillation in China.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly recommended over warfarin in stroke prevention for patients with non-valvular atrial fibrillation (AF). However, there is an important evidence gap in choosing the most appropriate DOAC for Chinese patients in clinical practice. METHODS: A multi-criteria decision analysis (MCDA) was adopted to build a scoring framework. Attributes and criteria were identified and determined by a scoping literature review, two rounds of Delphi surveys, and a consensus meeting. Weights of each attribute and criterion in the framework were determined using analytic hierarchy process (AHP). Evidence was collected based on the domestic or at least Asian data. Scoring methods for each criterion were developed depended on their characteristics and determined with an expert consensus meeting. Comprehensive scores of each DOAC were calculated based on the utility scores of each criterion and their corresponding weights. RESULTS: A total of 5 attributes, including safety, efficacy, costs/cost-effectiveness, suitability, and accessibility, were determined, and 16 criteria were under the 5 attributes. The safety and efficacy were ranked as the top two important attributes with the weights of 38.8% and 35.9%, respectively, while the suitability received the lowest weight of 7.9%. The comprehensive score for edoxaban was the highest (72.3), followed by dabigatran (49.7), rivaroxaban (37.9), and apixaban (35.8). CONCLUSIONS: This study provided a scoring framework developed for comprehensive evaluation of DOACs in China. The ranking of DOACs could help to support the decision-making in clinical practice. The framework could provide a reference for comprehensive evaluation of other drugs.

Efficacy of N-acetylcysteine plus pirfenidone in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

BACKGROUND: Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: RCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated. RESULTS: Two independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty). CONCLUSION: Moderate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.

Cabotegravir (Apretude) for Pre-exposure Prophylaxis for HIV Type 1 Infection.

Cabotegravir (Apretude) is an extended-release injectable HIV type 1 (HIV-1) antiretroviral integrase strand transfer inhibitor. Cabotegravir is labeled for use in adults and adolescents weighing at least 35 kg (77 lb) who are HIV-negative but at risk of HIV-1. It is used as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection, the most common form of HIV.1.

Efficacy of Pirfenidone and Nintedanib in Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis: A Systematic Review.

Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use worldwide. These drugs have been shown to reduce the rate of decline in forced vital capacity and the risk of acute exacerbation among patients with idiopathic pulmonary fibrosis. Recent data suggest that different interstitial lung diseases with a progressive pulmonary fibrosis phenotype can share similar pathogenetic and biological pathways and could be amenable to antifibrotic therapies. Indeed, historical management strategies in interstitial lung disease have failed to identify potential treatments once progression has occurred despite available drugs. In this systematic review, we summarized data on the efficacy of pirfenidone and nintedanib in interstitial lung diseases other than idiopathic pulmonary fibrosis as well as ongoing and upcoming clinical trials. We identify two well-designed trials regarding nintedanib demonstrating the efficacy of this drug in slowing disease progression in patients with interstitial lung diseases other than idiopathic pulmonary fibrosis. On the other hand, results on the use of pirfenidone in interstitial lung diseases other than idiopathic pulmonary fibrosis should be interpreted with more caution on the basis of trial limitations. Several randomized control trials are underway to improve the quality of evidence in the interstitial lung disease field.

[News in HIV infection, long-acting injectable treatments]. / VIH : zoom sur les traitements injectables à longue durée d'action.

Long-acting injectable therapies have been added to the pharmacological arsenal available for the management of HIV infection, whether in the form of monotherapy (injectable cabotegravir) as part of pre-exposure prophylaxis (PrEP) or dual therapies (injectable cabotegravir/rilpivirine) for the treatment of HIV. These treatments are the subject of new international recommendations following the publication of pivotal trials, the results of which will be presented in this review. We will also discuss the practical modalities of their implementation as well as the challenges to be faced in the future.

Les traitements injectables à longue durée d'action complètent les options pharmacologiques disponibles dans la prise en charge de l'infection par le VIH, que ce soit sous la forme de monothérapie (cabotégravir injectable) en prophylaxie pré-exposition (PrEP) ou de bithérapie (cabotégravir/rilpivirine injectables) en traitement. Ces molécules font l'objet de nouvelles recommandations internationales suite à la publication d'essais déterminants dont les résultats sont détaillés dans cet article. Nous abordons également les modalités pratiques de leur implémentation ainsi que les défis auxquels nous devons nous préparer.

[Pharmacotherapy: New drugs and vaccines in 2022]. / Pharmacothérapie - Nouveaux médicaments et vaccins disponibles en 2022.

A selection of drugs and vaccines newly available in Switzerland is reviewed. Shingrix: recombinant shingles vaccine recommended for all patients ≥65 years and some immunosuppressed patients. Nirmaltrevir/ritonavir: oral treatment of SARS-CoV-2 with a high potential of drug-drug interactions. Tixagevimab/cilgavimab: antibody combination for pre-exposure prophylaxis of SARS-CoV-2 in subjects without vaccine response or contraindication to vaccine. Cabotegravir/rilpivirine: 1st long-acting injectable treatment for HIV. Imvanex: monkeypox vaccine for subjects most at risk. Tezepelumab: first-in-class treatment for severe asthma. Eptinezumab: another anti-CGRP antibody for the prevention of migraine. Ponesimod: multiple sclerosis treatment with the advantage of a shorter half-life than fingolimod or ozanimod.

Une sélection de nouveaux médicaments et vaccins disponibles en Suisse est passée en revue. Shingrix : vaccin recombinant du zona recommandé chez les ≥ 65 ans et certains immunosupprimés. Nirmaltrevir/ritonavir : traitement oral du SARS-CoV-2 à haut potentiel d'interactions. Tixagévimab/cilgavimab : anticorps pour la prophylaxie préexposition du SARS-CoV-2 chez des sujets sans réponse vaccinale ou avec contre-indication au vaccin. Cabotégravir/rilpivirine : premier injectable à longue durée d'action contre le VIH. Imvanex : vaccin contre la variole du singe destiné aux sujets les plus à risque. Tézépélumab : premier traitement de sa classe pour l'asthme grave. Eptinézumab : un anticorps anti-CGRP de plus pour la prévention des migraines. Ponésimod : pour traiter la sclérose en plaques, avec l'avantage d'une plus courte demi-vie que le fingolimod ou l'ozanimod.