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Author(s): Atreyo Chakraborty [1] Introduction[sup.[1]] Pre- and post-exposure prophylaxis has been gaining interest in the recent decade for the prevention of various sexually transmitted diseases. This is partly fuelled by [...]

Background: Cabotegravir (CAB)/rilpivirine (RPV) is the first long-acting injectable (LAI) antiretroviral therapy approved for virologically suppressed adults with HIV-1. Setting: Italian single centre cohort. Methods: We conducted a retrospective observational study to assess the durability, adherence to the prescribed injection schedule, and reasons for discontinuation of CAB/RPV LAI administered every 8 weeks (Q8W). Results: One hundred thirty-eight patients were included with a median observation period of 43 weeks [interquartile range (IQR) 34-47 weeks]. Of these, 32 (23.2%) were female, and the median age was 51 years (IQR 40-58 years). Twelve patients (8.7%) discontinued CAB/RPV LAI treatment with a median time to discontinuation of 21 weeks (IQR 12-35 weeks), and 92.8% of the injections occurred within the CAB/RPV LAI schedule. The most common reason for discontinuation was injection-related pain (5/12). No confirmed virological failure occurred during the period of observation with 3 individuals who experienced virological blips. Conclusions: Our findings showed that CAB/RPV LAI Q8W is tolerated well in clinical practice, with high adherence to the injection schedule and few discontinuations mainly related to injection site--related pain. [ABSTRACT FROM AUTHOR]

Background: Despite the effectiveness of the TRIO regimen in maintaining viral suppression, as seen in the ANRS 139 TRIO trial, one drawback is the high pill burden. However, with the development of newer antiretrovirals, this regimen can be simplified. The combination of both co-formulated darunavir/cobicistat and dolutegravir/rilpivirine keeps the integrity of the TRIO regimen while decreasing daily pill count from 12 to 2 tablets daily. The purpose of this case series is to demonstrate the efficacy of this regimen as there is a current lack of data. Methods: This case series included patients with no resistance to dolutegravir, rilpivirine, or darunavir, who were switched to the modified TRIO regimen between June 1st 2018 to June 1st 2022. The primary outcome was the proportion of patients with plasma HIV-RNA levels <50 copies/mL by 24 weeks. Results: At week 24, all patients (n = 9) had a HIV-RNA <50 copies/mL. At week 48, one patient did not have a VL available. However, out of the remaining 8 patients, all maintained an HIV-RNA of <50 copies/mL at week 48. Conclusion: HIV-RNA levels remained suppressed when patients were switched to the modified TRIO regimen. In addition, the pill burden was reduced which can add to overall patient satisfaction. [ABSTRACT FROM AUTHOR]

Purpose Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) was approved for use in virally suppressed patients with human immunodeficiency virus (HIV) in January 2021. While this was a paradigm shift for many patients living with HIV, as LA-CAB/RPV was the first injectable complete regimen for the treatment of HIV, several patient populations, including those lacking virologic suppression, have not been able to easily access this advance in science and care. Summary In this article, we provide an update on 2 patients from our previous report and describe one further patient who experienced treatment failure following initiation of LA-CAB/RPV. Additionally, we review reports published to date of the clinical outcomes of patients with viremia who have accessed LA-CAB/RPV in the setting of baseline resistance-associated mutations (RAMs) to either component and any resulting RAMs at virologic failure. On the basis of this evidence, we recommend that hybrid or all-injectable regimens be considered for patients who have struggled with adherence to oral antiretroviral therapy or have partial or full resistance to one component of LA-CAB/RPV. Conclusion The case series reported here adds to literature supporting the notion that LA-CAB/RPV can be successfully used in patients who are viremic. [ABSTRACT FROM AUTHOR]

Introduction Cabotegravir, an integrase strand transfer inhibitor, and rilpivirine, an NNRTI, constitute the first long-acting (LA), injectable, two-drug ART regimen approved for the maintenance of virological suppression in persons living with HIV-1 (PLHIV). The aim of this study was to assess clinical effectiveness and tolerability of LA cabotegravir/rilpivirine in a real-world setting. Patients and methods We conducted a retrospective, single centre study, including all PLHIV receiving LA cabotegravir/rilpivirine as standard-of-care in our tertiary centre even if initiated in clinical trials. Results Between 2014 and 2022, 126 PLHIV initiated LA cabotegravir/rilpivirine. All were ART-experienced, and 98.4% had a viral load (VL) of <50 copies/mL before LA cabotegravir/rilpivirine initiation. Median BMI at cabotegravir/rilpivirine initiation was 24 IQR (23–28). During a median follow-up of 9 months IQR (7–24), 27 patients discontinued cabotegravir/rilpivirine: 5 because of virological failure, 6 for adverse events, 11 for personal reasons unrelated to treatment tolerance and 5 for other reasons. Virological failure was not associated with a higher BMI, nor with weight gain during LA intramuscular (IM) cabotegravir/rilpivirine treatment, inadequate cabotegravir and rilpivirine concentrations, VL blips or the use of oral lead-in (OLI) or not. No drug resistance-associated mutation emerged. Adverse events leading to treatment interruption were injection-site pain (n  = 3) and neuropsychological side effects (n  = 3). A correlation between BMI and both cabotegravir and rilpivirine concentrations at 1 month post-initiation of LA-IM cabotegravir/rilpivirine was observed, with no impact of OLI. Conclusions Data from this real-world cohort of PLHIV who received cabotegravir/rilpivirine LA injections suggest that this regimen is effective and well tolerated. Virological failures were not associated with the acquisition of resistance mutations. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Tenofovir alafenamide (TAF) was introduced in the European Union in 2015 as a novel prodrug of tenofovir showing similar efficacy in clinical trials and a more favorable safety profile than tenofovir disoproxil fumarate (TDF). The German TAFNES cohort study (2016–2019) was conducted to generate real‐world evidence.Treatment‐naïve (TN) and treatment‐experienced (TE) people with HIV (PWH) receiving elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF), rilpivirine/F/TAF (R/F/TAF) or F/TAF + 3rd agent were included. Month (M) 24 outcomes included virologic effectiveness (HIV RNA <50 copies/mL), treatment persistence, adverse drug reactions (ADRs) and patient‐reported outcomes, using the HIV Symptom Index (HIV‐SI), 36‐Item Short Form Health Survey (SF‐36) and HIV Treatment Satisfaction (HIVTSQ) questionnaires.The study included 767 PWH (92% men, median age 46 years; 301 TN, 466 TE; E/C/F/TAF [n = 318], R/F/TAF [n = 192], F/TAF + 3rd agent [n = 257]). Among TN, 35% had late HIV diagnosis (CD4 < 350/μL and/or AIDS). Of TE, 95% were on suppressive antiretroviral therapy (ART) before switching. D:A:D (Data Collection on Adverse Effects of Anti‐HIV Drugs) 5‐year risks for chronic kidney disease were high for about 1 in 10 TN and 4 in 10 TE. Overall treatment persistence at M24 was 81% (E/C/F/TAF: 88%; R/F/TAF: 86%; F/TAF + 3rd agent: 70%, with ART simplification of multiple‐tablet regimens in 13%). M24 viral suppression (missing = excluded) was 96% (479/501). Discontinuations due to virologic failure or ADRs were rare, 2% (12/767) and 4% (30/767), respectively. HIV‐SI and SF‐36 summary scores improved in TN; HIVTSQ change scores showed an improvement in treatment satisfaction in TE.Real‐world data confirmed a favorable safety profile and high virologic effectiveness with high treatment satisfaction on F/TAF‐based ART. [ABSTRACT FROM AUTHOR]

The article discusses the comparative use of tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) for human immunodeficiency virus (HIV) treatment. Topics discussed include the efficacy and safety profiles of TDF and TAF, their effects on body weight and metabolic health, and considerations for treatment in specific populations, such as those with advanced HIV disease and pregnant women.

Background Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). Although weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study. Methods We included participants who received at least 6 months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: (1) tenofovir disoproxil fumarate (TDF)-based ART, (2) dolutegravir/lamivudine (DTG/3TC), or (3) long-acting cabotegravir/rilpivirine (CAB/RPV). Results Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued, and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of −0.54 kg (95% confidence interval [CI] −.98 to −.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of −1.84 kg (95% CI −2.72 to −.97), and to a decrease in mean total cholesterol (−0.44 mmol/L) and triglycerides (−0.38 mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (−0.17 kg, 95% CI −.82 to.48) or long-acting CAB/RPV (−0.64 kg, 95% CI −2.16 to.89) did not lead to reductions in weight. Conclusions Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within 1 year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV. [ABSTRACT FROM AUTHOR]

Background Implementation level of long-acting injectable agents cabotegravir/rilpivirine (LAI CAB/RPV) for human immunodeficiency virus (HIV) treatment in Italy is still not known. The aim of this study is to identify the status of implementation of LAI CAB-RPV and its barriers. Materials and methods A cross-sectional online survey was conducted among infectious diseases (ID) physicians and nurses belonging to the ICONA network in Italy. Three validate 4-items measures were used: Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM). Results Out of 61 ICONA centres, 38 (62%) completed the survey: 57.9% were academic centres, 42.1% were hospital-based. In total, 104 respondents were ID physicians (57.4%), 77 were nurses (42.5%); 4.5% of all PWH followed at the 38 centres started LAI CAB/RPV at time of study. Centres taking care of >1000 PWH reported 95% application of procedures for LA implementation, higher than other centres (P  = 0.009). Mean score of AIM was (16.0, standard deviation, SD, 3.3), of IAM (16.0, SD 3.0) and FIM (16.0, SD 2.9). A linear correlation was found between AIM and the number of people with HIV who started LAI CAB/RPV (25–50 versus <25, coefficient of correlation [b] 2.57, 95%CI 0.91–4.60, P  = 0.004), academic versus hospital-based centres (b −1.59, 95%CI −2.76–0.110044, P  = 0.007) and the absence of preliminary systematic assessment of staff (b −1.98, 95%CI −3.31–0.65, P  = 0.004). Implementation barriers were not significantly different according to the number of PWH/centre. Conclusions LAI CAB/RPV implementation was low, with a great variability according to centre size. Tailored and centre-specific interventions to address barriers and to optimize the LA treatment implementation should be designed. [ABSTRACT FROM AUTHOR]

The article examines the use of long-acting injectable cabotegravir and rilpivirine for individuals with HIV, comparing its effectiveness to standard oral treatment. While clinical trials show promising results, concerns exist regarding the development of drug resistance in case of virological failure. Real-world data supports the regimen's efficacy, but further research is needed for long-term confirmation. The text underscores the necessity of thorough virological monitoring, prompt action in case of failure, and informed decision-making for patients considering this treatment option. [Extracted from the article]

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]

Abstract Background Antiretroviral therapy (ART) for HIV infection has evolved substantially. The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB + RPV). Methods This prospective cohort study included PLWH aged 18 years and older who switched to CAB + RPV and received the injections every 8 weeks between June 2022 and May 2023, after a 4-week oral lead-in phase. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 44 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was used to estimate changes in clinical data from baseline. Results Thirty-eight male participants were enrolled. Some participants had detectable levels of viral replication; however, all participants maintained viral suppression (HIV-RNA

Background: Antiretroviral therapy (ART) for HIV infection has evolved substantially. The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB + RPV). Methods: This prospective cohort study included PLWH aged 18 years and older who switched to CAB + RPV and received the injections every 8 weeks between June 2022 and May 2023, after a 4-week oral lead-in phase. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 44 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was used to estimate changes in clinical data from baseline. Results: Thirty-eight male participants were enrolled. Some participants had detectable levels of viral replication; however, all participants maintained viral suppression (HIV-RNA < 50 copies/mL) at 44 weeks and no cases of virological failure were detected. The creatinine level decreased by − 0.04 mg/dL (95% confidence interval [CI]: − 0.07 to − 0.01), lipid and glucose profiles remained stable, and treatment satisfaction increased by 6.6 points (95% CI: 2.4 to 10.8) after switching to CAB + RPV. Conclusions: Long-acting ART provides effective viral suppression and enhances treatment satisfaction in PLWH switching from conventional ART. Long-acting ART can improve patient well-being; however, patient selection and monitoring to prevent HBV-related complications are important. [ABSTRACT FROM AUTHOR]

Virologic failure of long-acting rilpivirine/cabotegravir is rare but may result in severely limited treatment options. Known risk factors cannot predict all cases. Therapeutic drug monitoring (TDM) may help identify patients at risk, but reliable thresholds are missing. We report retrospective TDM in a cohort of 5 patients, including 1 virological failure. [ABSTRACT FROM AUTHOR]

Long‐acting injectable (LAI) cabotegravir and rilpivirine for HIV treatment and LAI cabotegravir for pre‐exposure HIV prophylaxis are being rolled out in a multitude of countries worldwide. Due to the prolonged exposure, it can be challenging to undertake 'traditional' pharmacokinetic studies and current guidance is derived from their oral equivalents or physiologically based pharmacokinetic studies. This review aims to consider pharmacokinetic characteristics of cabotegravir and rilpivirine and describe anticipated drug–drug interactions (DDIs) with frequent concomitant medications in African settings. Relevant co‐medications were identified from the WHO 2021 List of Essential Medicines. All original human and physiologically based pharmacokinetic studies published in English on PubMed, discussing DDIs with LAI cabotegravir and rilpivirine prior to April 2023, were reviewed. The Liverpool HIV interaction database was also reviewed (https://www.hiv-druginteractions.org/checker). LAI cabotegravir and rilpivirine have half‐lives of 6–12 and 13–28 weeks, respectively. Cabotegravir is primarily metabolized by UDP‐glucuronyltransferase (UGT)‐1A1 and rilpivirine by cytochrome P450 (CYP)‐3A4. LAI cabotegravir and rilpivirine themselves exhibit low risk of perpetrating interactions with co‐medications as they do not induce or inhibit the major drug metabolizing enzymes. However, they are victims of DDIs relating to the induction of their metabolizing enzymes by concomitantly administered medication. Noteworthy contraindicated co‐medications include rifamycins, carbamazepine, phenytoin, flucloxacillin and griseofulvin, which induce CYP3A4 and/or UGT1A1, causing clinically significant reduced concentrations of rilpivirine and/or cabotegravir. In addition to virologic failure, subtherapeutic concentrations resulting from DDIs can lead to emergent drug resistance. Clinicians should be aware of potential DDIs and counsel people receiving LAI cabotegravir/rilpivirine appropriately to minimize risk. [ABSTRACT FROM AUTHOR]

A monoclinic C form of rilpivirine hydrochloride, (N6H19C22)Cl, has been obtained and characterized using solid-state 15N, 13C, and 35Cl NMR spectroscopy and multitemperature synchrotron X-ray powder diffraction. The title compound crystallizes in the monoclinic system (space group C 2/ c , #15) at both room (295.0(2) K) and low (100.0(2) K) temperatures. At room temperature, the following parameters are a = 19.43051(3), b = 13.09431(14), c = 17.10254(18) Å, β = 109.3937(7), V = 4104.48(9) Å3, and Z = 8. The folded molecular conformation of the cation is similar with that of free base rilpivirine with the exception of cyanovinyl group disposition. The anion links cations to infinite chains parallel to the crystallographic c axis using N–H⋯Cl bonds where both amino groups and the protonated pyrimidine ring take part in the H-bonding. The powder patterns have been submitted to the ICDD for inclusion in the Powder Diffraction File™ (PDF®). [ABSTRACT FROM AUTHOR]

Background: Cabotegravir + rilpivirine long-acting (CAB + RPV LA) dosed every 2 months (Q2M) is a complete regimen for the maintenance of HIV-1 virologic suppression. In this study, we report month 12 clinical outcomes in patient study participants (PSPs) in the CAB and RPV Implementation Study in European Locations (CARISEL) study. Setting: CARISEL is a phase 3b implementation-effectiveness study. Methods: CARISEL was designed as a 2-arm, unblinded study with centers randomized to either enhanced or standard implementation arms. For PSPs, this study is single arm, unblinded, and interventional; all PSPs switched from daily oral therapy to CAB + RPV LA dosed Q2M. The primary objective was to evaluate the perceived acceptability, appropriateness, and feasibility of CAB + RPV LA implementation for staff participants (presented separately). Clinical secondary endpoints assessed through month 12 included the proportion of PSPs with plasma HIV-1 RNA ≥50 and <50 copies/mL (Snapshot algorithm), incidence of confirmed virologic failure (CVF; 2 consecutive plasma HIV-1 RNA levels ≥200 copies/mL), adherence to injection visit windows, and safety and tolerability. Results: Four hundred thirty PSPs were enrolled and treated; the mean age was 44 years (30% ≥50 years), 25% were women (sex at birth), and 22% were persons of color. At month 12, 87% (n = 373/430) of PSPs maintained HIV-1 RNA <50 copies/mL, with 0.7% (n = 3/430) having HIV-1 RNA ≥50 copies/mL. One PSP had CVF. The safety profile was consistent with previous findings. Overall, the results were similar between implementation arms. Conclusion: CAB + RPV LA Q2M was well tolerated and highly effective in maintaining virologic suppression with a low rate of virologic failure. [ABSTRACT FROM AUTHOR]

Background Obesity is increasingly prevalent among people with human immunodeficiency virus (HIV, PWH). Obesity can reduce drug exposure; however, limited data are available for long-acting (LA) antiretrovirals. We performed in silico trials using physiologically based pharmacokinetic (PBPK) modeling to determine the effect of obesity on the exposure of LA cabotegravir and rilpivirine after the initial injection and after multiple injections. Methods Our PBPK model was verified against available clinical data for LA cabotegravir and rilpivirine in normal weight/ overweight (body mass index [BMI] <30 kg/m2) and in obese (BMI > 30 kg/m2). Cohorts of virtual individuals were generated to simulate the exposure of LA cabotegravir/rilpivirine up to a BMI of 60 kg/m2. The fold change in LA cabotegravir and rilpivirine exposures (area under the curve [AUC]) and trough concentrations (Cmin) for monthly and bimonthly administration were calculated for various BMI categories relative to normal weight (18.5–25 kg/m2). Results Obesity was predicted to impact more cabotegravir than rilpivirine with a decrease in cabotegravir AUC and Cmin of >35% for BMI >35 kg/m2 and in rilpivirine AUC and Cmin of >18% for BMI >40 kg/m2 at steady-state. A significant proportion of morbidly obese individuals were predicted to have both cabotegravir and rilpivirine Cmin below the target concentration at steady-state with the bimonthly administration, but this was less frequent with the monthly administration. Conclusions Morbidly obese PWH are at risk of presenting suboptimal Cmin for cabotegravir/rilpivirine after the first injection but also at steady-state particularly with the bimonthly administration. Therapeutic drug monitoring is advised to guide dosing interval adjustment. [ABSTRACT FROM AUTHOR]

Objectives: The inJectable Antiretroviral feasiBility Study (JABS) aimed to evaluate the implementation of long‐acting regimens in a 'real world' Australian setting, with inclusion of participants with complex medical needs, social vulnerability and/or historical non‐adherence. Methods: JABS was a 12‐month, single‐centre, single‐arm, open‐label phase IV study of long‐acting cabotegravir 600 mg plus rilpivirine 900 mg administered intramuscularly every 2 months to adults with treated HIV‐1 infection. The primary endpoint was the proportion of attendances and administration of injections within a 14‐day dosing window over 12 months, out of the total prescribed doses. Secondary endpoints included proportions of missed appointments, use of oral bridging, discontinuations, virological failures, adverse events and participant‐reported outcomes. A multidisciplinary adherence programme embedded in the clinical service known as REACH provided support to JABS participants. Results: Of 60 participants enrolled by May 2022, 60% had one or more complexity or vulnerability factors identified, including absence of social supports (50%), mental health issues, alcohol or drug use (30%) and financial hardship or instability (13%), among others. Twenty‐seven per cent of participants had historical non‐adherence to antiretroviral therapy. Out of 395 prescribed doses, 97.2% of injections were administered within correct dosing windows at clinic visits. Two courses of short‐term oral bridging were required. The rate of injection site reactions was 29%, the majority being grade 1–2. There were no virological failures, no serious adverse events and only one injection‐related study discontinuation. High baseline treatment satisfaction and acceptability of injections increased by month 12. Those with vulnerability factors had similar adherence to injections as those without such factors. Ninety‐eight per cent of the participants who completed 12 months on the study have maintained long‐acting therapy, virological suppression and retention in care. Conclusions: Long‐acting cabotegravir plus rilpivirine was associated with very high adherence, maintenance of virological suppression, safety and treatment satisfaction in a diverse Australian clinic population, comparable to results of phase III randomized clinical trials. Individuals with vulnerability factors can achieve adherence to injections with individualized support. Long‐acting therapies in this group can increase the subsequent engagement in clinical care. [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]

This study focused on the preparation and characterization of rilpivirine-loaded nanobilosomes. Formulations were developed using rilpivirine, phosphatidylcholine S-100 (SPC), and sodium deoxycholate (SDC) via the thin film hydration method. The nanobilosomes were characterized for vesicle size, polydispersity index (PDI), surface charge, and entrapment efficiency (%EE). Thermal behavior and drug-excipient interactions were analyzed using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Transmission electron microscopy (TEM) revealed that BS-06 nanobilosomes possess a smooth and uniform surface morphology. In vitro cytotoxicity assays were conducted on HeLa and HEK 293 cell lines, and minimum inhibitory concentration (MIC) was assessed against S. aureus and E. coli. Stability was monitored over 3 months at various temperatures. The optimized formulation (BS-06) exhibited a vesicle size of 132.8 ± 4.0 nm, a zeta potential of -30.10 ± 0.8 mV, and a PDI of 0.20, demonstrating optimal surface characteristics and maximum entrapment efficiency. In vitro release studies indicated a maximum drug release of 84.81 ± 4.6% over 24 h. Cytotoxicity studies showed that BS-06 improved cell viability in HeLa and HEK 293 cell lines at 24 and 48 h and enhanced antibacterial activity against S. aureus and E. coli. Overall, our findings highlight the potential of rilpivirine-loaded nanobilosomes as a promising drug delivery system for HIV/AIDS, with enhanced dissolution, stability and biocompatibility. [ABSTRACT FROM AUTHOR]

Background Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation. Methods We performed an in-depth clinical, virological, and pharmacokinetic analysis on the reasons behind and the impact of VF during LA CAB/RPV therapy in 5 cases from the Netherlands. Genotypic resistance testing was performed after the occurrence of VF, and drug plasma (trough) concentrations were measured after VF was established and on any other samples to assess on-treatment drug levels. CAB and RPV drug levels that were below the first quartile of the population cutoff (≤Q1) were considered to be low. Results Five cases who were eligible for LA CAB/RPV experienced VF despite a low predicted risk at baseline. Genotypic resistance testing revealed extensive selection of nonnucleoside reverse transcriptase inhibitor–associated mutations in all cases, and integrase strand transfer inhibitor mutations in 4 cases. All cases displayed low drug levels of either CAB, RPV, or both during the treatment course, likely contributing to the occurrence of VF. In 3 cases, we were able to identify the potential mechanisms behind these low drug levels. Conclusions This is the first in-depth multiple case analysis of VF on LA CAB/RPV therapy in a real-world setting. Our observations stress the need to be aware for (evolving) risk factors and the yield of a comprehensive clinical, virological, and pharmacokinetic approach in case of failure. [ABSTRACT FROM AUTHOR]

Background Cabotegravir plus rilpivirine (CAB + RPV) is a guideline-recommended long-acting (LA) injectable regimen for the maintenance of human immunodeficiency virus-1 (HIV-1) virologic suppression. This post hoc analysis summarizes CAB + RPV LA results by baseline body mass index (BMI) category among phase 3/3b trial participants. Methods Data from CAB + RPV-naive participants receiving every 4 or 8 week dosing in FLAIR, ATLAS, and ATLAS-2M were pooled through week 48. Data beyond week 48 were summarized by study (FLAIR through week 96 and ATLAS-2M through week 152). HIV-1 RNA <50 and ≥50 copies/mL, confirmed virologic failure (CVF; 2 consecutive HIV-1 RNA ≥200 copies/mL), safety and tolerability, and plasma CAB and RPV trough concentrations were evaluated by baseline BMI (<30 kg/m2, lower; ≥30 kg/m2, higher). Results Among 1245 CAB + RPV LA participants, 213 (17%) had a baseline BMI ≥30 kg/m2. At week 48, 92% versus 93% of participants with lower versus higher BMI had HIV-1 RNA <50 copies/mL, respectively. Including data beyond week 48, 18 participants had CVF; those in the higher BMI group (n = 8) all had at least 1 other baseline factor associated with CVF (archived RPV resistance-associated mutations or HIV-1 subtype A6/A1). Safety and pharmacokinetic profiles were comparable between BMI categories. Conclusions CAB + RPV LA was efficacious and well tolerated, regardless of baseline BMI category. Clinical Trials Registration NCT02938520, NCT02951052, and NCT03299049. [ABSTRACT FROM AUTHOR]

Introduction: Cabotegravir plus rilpivirine (CAB + RPV) is the first complete long‐acting (LA) regimen recommended for maintaining HIV‐1 virological suppression. Cabotegravir And Rilpivirine Implementation Study in European Locations (CARISEL) is an implementation–effectiveness study examining the implementation of CAB+RPV LA administered every 2 months (Q2M) in European HIV centres. We present staff study participant (SSP) perspectives on the administration of CAB+RPV LA over 12 months. Methods: Eighteen clinics were randomized to one of two implementation support packages: standard arm (Arm‐S) or enhanced arm (Arm‐E). Arm‐S included video injection training and provider/patient toolkits. Additionally, Arm‐E included skilled wrap‐around team meetings, face‐to‐face injection training and continuous quality improvement (CQI) calls. SSPs completed surveys on the acceptability, appropriateness and feasibility of CAB+RPV LA as an intervention and its implementation into their clinics, as well as barriers and facilitators to implementation. All surveys were completed at Month (M)1 (baseline), M5 and M12; data collection was completed by February 2022. Qualitative data were obtained from semi‐structured interviews at M1, M5 and M12. The primary objective was assessed via formal statistical comparisons between study arms of the Acceptability of Implementation Measure, Implementation Appropriateness Measure and Feasibility of Implementation Measure surveys (1–5 Likert scale ranging from 1 = "completely disagree" to 5 = "completely agree"). Equivalent measures anchored to CAB+RPV LA as a therapy were also assessed. Results: Seventy SSPs completed surveys and interviews at M1, 68 at M5 and 62 at M12. Mean acceptability/appropriateness/feasibility scores were ≥3.8 (out of 5) at M12 for implementation‐ and intervention‐based measures. An analysis of covariance showed no significant differences between study arms for these outcomes. Although barriers were noted, most SSPs were not overly concerned that these would impact implementation; concern about these anticipated barriers also decreased over time. At M12, 90.3% (n = 56/62) of SSPs held a positive opinion about CAB+RPV LA implementation. Qualitative interviews and CQI calls highlighted three top practices that supported implementation: implementation planning; education about CAB+RPV LA clinical efficacy; and education around administering injections and managing pain/discomfort after injections. Conclusions: CARISEL demonstrated that CAB+RPV LA dosed Q2M was successfully implemented across a range of European locations, with SSPs finding implementation highly acceptable, appropriate and feasible. ClinicalTrials.gov number: NCT04399551 [ABSTRACT FROM AUTHOR]