48-week viral suppression rates in people with HIV starting long-acting CAB/RPV with initial viremia.

BACKGROUND: We previously demonstrated at the Ward 86 HIV clinic in San Francisco that long-acting cabotegravir/rilpivirine (LA-CAB/RPV) can rapidly lead to viral suppression (VS) in people with HIV (PWH) with viremia due to adherence challenges. We now evaluate VS durability in this population. METHODS: We conducted a retrospective cohort study of PWH who started LA-CAB/RPV with viremia (HIV RNA viral load [VL]≥50 copies/mL) before December 2022. Our primary outcome was VS (VL<50 copies/mL) with LA-CAB/RPV persistence (not discontinued or late by >14 days) at 48 weeks, using the closest VL to 48+/-8 weeks. We also describe viral failure (VF), defined as <2-log VL decline at 4 weeks or VL≥200 copies/mL after initial VS with emergent CAB- or RPV-associated resistance mutations; and overall 48-week VS including those switched to alternative ART. RESULTS: Fifty nine PWH initiated LA-CAB/RPV with viremia and were included in analysis; 49% had CD4<200 cells/µL and median baseline VL was 42,900 copies/mL (Q1-Q3 5,272-139,038). At 48 weeks, 47 met the primary outcome of VS with LA-CAB/RPV persistence (80%; 95%CI 67-89%). Five had VF with resistance (three with RPV-associated mutations, two with CAB and RPV-associated mutations) and one was lost-to-follow-up. At week 48, two of those with VF were suppressed on alternative regimens (lenacapavir+BIC/TAF/FTC and CAB+lenacapavir). Overall week 48 VS on either LA-CAB/RPV or alternative ART was 92% (54/59). CONCLUSIONS: In PWH initiating LA-CAB/RPV with initial viremia, 48-week VS (<50 copies/mL) was 92%. Long-acting ART can be an important tool for improving VS among patients who face adherence challenges to oral ART.

Comparison of At-Home Versus In-Clinic Receipt of Long-Acting Injectable Cabotegravir/Rilpivirine.

BACKGROUND: The need for frequent travel to a clinic could impair access to injectable antiretroviral therapy for persons living with human immunodeficiency virus type 1 (HIV-1) infection. We hypothesized that allowing persons receiving treatment with long-acting injectable cabotegravir plus rilpivirine (LA CAB/RPV) to receive and store the medication in their own refrigerator prior to in-home administration by a healthcare provider would be as safe and effective as receiving treatment in a clinic. METHODS: Persons prescribed LA CAB/RPV in the Infectious Diseases clinic at the Medical University of South Carolina were offered enrollment in this non-randomized, observational study between August 2021 and December 2022. After in-clinic receipt of the initial LA CAB/RPV injection, participants chose to receive each subsequent injection over the following 12-months either in clinic or at home. RESULTS: The 33 enrolled participants were primarily Black (64%), male (73%), and had a median age of 46. Three participants stopped LA CAB/RPV and transitioned to oral antiretroviral therapy due to allergy (n = 1), loss of virologic suppression (n = 1), and visit adherence (n = 1) concerns. A comparable number of participants received treatment primarily in clinic (n = 18) relative to at home (n = 15). Injection site pain/soreness was common (52% of injections) but did not differ between groups. There were no differences in safety or efficacy between groups and both groups reported high treatment satisfaction. All participants were virologically suppressed and retained in care at the end of the study. CONCLUSIONS: At-home administration of LA CAB/RPV by a healthcare provider was comparably safe, effective, and associated with high participant satisfaction relative to in-clinic administration.

Improvements in Patient-Reported Outcomes After 12 Months of Maintenance Therapy With Cabotegravir + Rilpivirine Long-Acting Compared With Bictegravir/Emtricitabine/Tenofovir Alafenamide in the Phase 3b SOLAR Study.

SOLAR (NCT04542070; registered 2020-09-09) is a Phase 3b study that demonstrated the noninferior virological efficacy of switching to cabotegravir + rilpivirine long-acting (CAB + RPV LA) dosed every 2 months vs. continuing daily oral bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) over 12 months. Participants were randomised (2:1) to switch to CAB + RPV LA or to continue BIC/FTC/TAF. Patient-reported endpoints included treatment preference, treatment satisfaction (12-item HIV Treatment Satisfaction Questionnaire status version), acceptability of injections (Perception of Injection questionnaire [acceptability domain]) and three single-item questions exploring psychological challenges related to HIV treatment (fear of disclosure, adherence-related anxiety and reminder of HIV status). Of 670 participants, 447 participants switched to CAB + RPV LA and 223 continued BIC/FTC/TAF. Overall, 18% were female, median age was 37 years and 31% were non-White. At Month 12, CAB + RPV LA significantly improved treatment satisfaction vs. BIC/FTC/TAF (mean [95% confidence interval (CI)] change: + 3.36 [2.59, 4.13] vs. -1.59 [-2.71, -0.47]; p < 0.001). At Month 12, a higher proportion of CAB + RPV LA arm participants reported improvements across the psychological challenges related to HIV treatment questions compared with BIC/FTC/TAF participants. Participants indicating ≥ 1 psychological challenge at baseline experienced a statistically significant and clinically meaningful improvement in treatment satisfaction after 12 months of CAB + RPV LA vs. continuing BIC/FTC/TAF (adjusted difference [95% CI]: 7.96 [5.65, 10.26]; p < 0.001). Most (90%, 382/425) questionnaire respondents preferred CAB + RPV LA vs. BIC/FTC/TAF (5%, 21/425). Switching to CAB + RPV LA was associated with significantly improved treatment satisfaction and relief from the fear of disclosure, anxiety surrounding adherence and reminder of HIV status.

RESUMEN: SOLAR (NCT04542070; registrado el 09-09-2020) es un estudio de fase IIIb que ha demostrado la eficacia virológica no inferior de cambiar a cabotegravir+rilpivirina de acción prolongada (CAB+RPV LA) administrado cada 2 meses frente a continuar con la administración oral diaria de bictegravir/emtricitabina/tenofovir alafenamida (BIC/FTC/TAF) durante 12 meses. Los participantes fueron asignados de forma aleatoria (2:1) al grupo de cambio a CAB+RPV LA o de continuación con BIC/FTC/TAF. Los parámetros declarados por los pacientes incluían la preferencia del tratamiento, la satisfacción del tratamiento (versión del estado del cuestionario de satisfacción del tratamiento de VIH de 12 preguntas), la aceptación de las inyecciones (cuestionario de percepción de las inyecciones [dominio de aceptación]) y tres preguntas individuales que analizaban los problemas psicológicos relacionados con el tratamiento del VIH (miedo a la revelación, ansiedad relacionada con el cumplimiento terapéutico y recordatorio del estado del VIH). De los 670 participantes, 447 participantes cambiaron a CAB+RPV LA y 223 continuaron con BIC/FTC/TAF. En general, el 18 % eran mujeres, el promedio de edad era de 37 años y el 31 % no eran blancos. En el mes 12, el tratamiento con CAB+RPV LA aumentó considerablemente la satisfacción del tratamiento frente al BIC/FTC/TAF (cambio [intervalo de confianza (IC) del 95 %] medio: +3.36 [2.59; 4.13] frente a ­1.59 [­2.71; ­0.47]; p<0.001). En el mes 12, una mayor proporción de participantes del grupo de CAB+RPV LA declararon mejoras en todos los problemas psicológicos relacionados con las preguntas sobre el tratamiento del VIH en comparación con los participantes del grupo de BIC/FTC/TAF. Los participantes que indicaron ≥ 1 problema psicológico en el inicio experimentaron una mejora importante estadísticamente y significativa clínicamente con respecto a la satisfacción del tratamiento al cabo de 12 meses del cambio a CAB+RPV LA frente a la continuación con BIC/FTC/TAF (diferencia ajustada [IC del 95 %]: 7.96 [5.65; 10.26]; p<0.001). La mayoría de encuestados (el 90 %, 382/425) preferían CAB+RPV LA frente a BIC/FTC/TAF (el 5 %, 21/425). El cambio a CAB+RPV LA se asoció a un aumento considerable de la satisfacción del tratamiento y al alivio del miedo a la revelación, la ansiedad en torno al cumplimiento terapéutico y el recordatorio del estado del VIH.

Therapeutic failure reported with HIV long-acting injectables: An analysis of the FDA Adverse Event Reporting System from 2021 to 2024.

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

Virological History Predicts Non-sustained Viral Suppression with Long-Acting Cabotegravir and Rilpivirine Therapy, independent of Pharmacokinetic Parameters.

BACKGROUND: This study aimed to investigate factors contributing to non-sustained viral suppression, including intermittent viremia and persistent low-level viremia, during cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) injectable therapy, with a focus on pharmacokinetics (PK). METHODS: A prospective cohort study was conducted on people with HIV (PWH) transitioning from stable oral antiretroviral therapy (ART) to bimonthly CAB+RPV LA. Standardized follow-up included close monitoring through blood sampling for plasma HIV-1 viral load (VL) and multiple plasma drug concentrations measurements to analyze the connection between PK parameters and virologic outcomes. RESULTS: Among 173 patients with a median (IQR) follow-up of 11.1(7.1-13.2) months and 789 pre-dose measurements, 38.7% experienced VL≥20 copies/mL, and 16.2% had levels ≥50 copies/mL. Intermittent viremia occurred in 34.7% of patients, and persistent low-level viremia in 4%. Virological failure developed in two cases. Predictors of non-sustained viral suppression included VL at HIV diagnosis [AHR: 1.49 per log10 VL, 95% CI: 1.04-2.12, P =.027], detectable viremia on oral ART [AHR: 2.45, 95% CI: 1.29-4.65, P =.006], and the level of viral suppression at transition [AHR: 0.38, 95% CI: 0.19-0.75, P =.004]. We found a significant association between low trough concentrations of CAB and RPV and episodes of detectable viremia exceeding 50 copies/mL. However, none of the assessed PK covariates predicted non-sustained viral suppression in multivariable models. CONCLUSION: Non-sustained viral suppression in PWH transitioning from stable oral ART to CAB+RPV LA was linked to pre-existing factors before transition. Higher VL pre-ART and incomplete suppression on oral therapy increased the risk, independent of PK parameters.

Long-acting antiretroviral therapy effectiveness and patient satisfaction using patient questionnaires: data from a real-world setting.

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.

Patient Participant Perspectives on Implementation of Long-Acting Cabotegravir and Rilpivirine: Results From the Cabotegravir and Rilpivirine Implementation Study in European Locations (CARISEL) Study.

INTRODUCTION: CARISEL is an implementation-effectiveness "hybrid" study examining the perspectives of people living with HIV-1 (patient study participants [PSPs]) on cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) dosed every 2 months (Q2M) across 5 European countries. METHODS: PSPs completed questionnaires on acceptability (Acceptability of Intervention Measure), appropriateness (Intervention Appropriateness Measure), and feasibility (Feasibility of Intervention Measure) at their first (Month [M] 1), third (M4), and seventh (M12) injection visits. Semistructured qualitative interviews were also conducted. RESULTS: Overall, 437 PSPs were enrolled, of whom 430 received treatment. Median (interquartile range) age was 44 (37-51) years, 25.3% (n = 109/430) were female (sex at birth), and 21.9% (n = 94/430) were persons of color. Across time points, PSPs found CAB + RPV LA highly acceptable, appropriate, and feasible (mean scores ≥4.47/5). Qualitative data supported these observations. CONCLUSIONS: PSPs found CAB + RPV LA Q2M to be an acceptable, appropriate, and feasible treatment option.

Therapeutic Drug Monitoring of Long-Acting Rilpivirine and Cabotegravir for Treatment of HIV-1 Infection-A Case Series of Five Patients With One Virologic Failure After Development of Two-Class Resistance.

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.

Process evaluation and early outcomes of real-world implementation of a pharmacist-driven cabotegravir/rilpivirine long-acting injectable initiative.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Patient and clinic staff perspectives on the implementation of a long-acting injectable antiretroviral therapy program in an urban safety-net health system.

BACKGROUND: Long-acting injectable cabotegravir plus rilpivirine (LAI CAB/RPV) has several potential benefits over daily oral formulations for HIV treatment, including the potential to facilitate long-term adherence and reduce pill fatigue. We aimed to assess facilitators of and barriers to LAI CAB/RPV implementation and delivery through the perspectives of physicians and clinical staff, and the experiences of LAI CAB/RPV use among people living with HIV (PLWH) at a Ryan-White supported safety-net clinic in North Texas. METHODS: We conducted semi-structured interviews with recruited clinic staff (physicians, nurses, and support staff) involved with LAI CAB/RPV implementation and PLWH who switched to LAI CAB/RPV and consented to participate in individual interviews. Data were collected from July to October 2023. Our interview guide was informed by the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM), and Proctor Implementation Outcomes frameworks. Qualitative data were analyzed using a rapid qualitative analysis approach to summarize key themes. RESULTS: We recruited and interviewed 15 PLWH who transitioned to LAI CAB/RPV and 11 clinic staff serving these patients. PLWH conveyed that emotional and informational support from family or a trusted clinician influenced their decision to switch to LAI CAB/RPV. PLWH also reported that injectable treatment was more effective, convenient, and acceptable than oral antiretroviral therapy. Clinic staff and physicians reported that staff training, pharmacist-led medication switches, flexible appointments, refrigeration space and designated room for injection delivery facilitated implementation. Clinic staff cited medication costs, understaffing, insurance prior authorization requirements, and lack of medication access through state drug assistance programs as critical barriers. CONCLUSIONS: Our study offers insights into real-world experiences with LAI usage from the patient perspective and identifies potential strategies to promote LAI CAB/RPV uptake. The barriers to and facilitators of LAI CAB/RPV program implementation reported by clinic staff in our study may be useful for informing strategies to optimize LAI CAB/RPV programs.

Potential healthcare resource use and associated costs of every 2 month injectable cabotegravir plus rilpivirine long-acting regimen implementation in the Spanish National Healthcare System compared to daily oral HIV treatments.

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.

Early Implementation and Outcomes Among People with HIV Who Accessed Long-Acting Injectable Cabotegravir/Rilpivirine at Two Ryan White Clinics in the U.S. South.

The use of long-acting injectable cabotegravir/rilpivirine (LAI-CAB/RPV) as maintenance therapy for persons with HIV (PWH), which may improve treatment access and outcomes, though real-world data on uptake are limited, was studied at two Ryan White clinics in Atlanta, Georgia. Among PWH referred from 4/1/2021 to 9/15/2022 to switch to LAI-CAB/RPV, characteristics were ascertained at time of referral; and disposition (initiated; ineligible; uninterested; pending) was recorded as of 9/15/2022. Among patients initiated on CAB/RPV, we assessed the drug procurement process and clinical outcomes through 6/1/2023. Among 149 PWH referred, 74/149 (50%) initiated CAB/RPV as of 9/15/2022, of whom, characteristics were median age 47 (Q1-Q3 36-55) years, 16% cisgender female, 72% Black race, median HIV duration 15 (Q1-Q3 9-19) years, and 64% had commercial health insurance. Of the 75 PWH not initiated, 35 were ineligible owing to a clinical concern (n = 16) or insurance issue (n = 19); 15 patients changed their mind about switching; and 25 were pending eligibility review or therapy initiation. Median time from CAB/RPV prescription to initiation was 46 (Q1-Q3 29-78) days. Of 731 total injections administered (median 11 injections/patient), 95% were given within 7 days of the target treatment date. Nearly all patients were virally suppressed upon referral and remained suppressed through follow-up. At two clinics in the U.S. South, half of the patients referred for LAI-CAB/RPV successfully accessed therapy nearly 2 years after U.S. drug approval. We identified barriers to uptake at the patient and structural levels, highlighting key areas to invest resource and personnel support to sustain and scale long-acting antiretroviral therapy programming.

Interference with mitochondrial function as part of the antifibrogenic effect of Rilpivirine: A step towards novel targets in hepatic stellate cell activation.

Activated hepatic stellate cells (aHSCs), the main perpetrators of liver fibrosis, are a promising therapeutic target in the treatment of chronic liver disease. During liver injury, HSCs transcend from a quiescent to a fibrotic phenotype, a process which involves major metabolic reprogramming with altered mitochondrial function. The antiretroviral drug Rilpivirine (RPV) has demonstrated a hepatoprotective and specifically antifibrotic effect in several animal models of chronic liver injury, as well as in vitro. Herein, we use HSCs activated with the profibrogenic cytokine TGF-ß to explore whether mitochondrial function is implicated in this effect. The mitochondrial bioenergetic profile, morphology and dynamics of TGF-ß-treated cells (48 h) were altered and these effects were prevented by co-treatment with clinically relevant concentrations of RPV. A MitoStress Test (Seahorse Analyzer) revealed that TGF-ß increased both oxygen consumption rate (basal respiration, maximal respiration and spare respiratory capacity) and extracellular acidification rate (indicative of increased glycolysis). Cells exposed to TGF-ß also displayed diminished mitochondrial membrane potential and enhanced mitochondrial fission. All of these effects were rescued with RPV. RNA sequencing analysis of cells exposed to TGF-ß revealed the presence of 338 differentially expressed genes that encode mitochondrial proteins (mito-DEGs), of which 139 and 199 were significantly up- and down-regulated (adjusted p<0.05). This alteration in 15 (10.79 %) and 31 (22.03 %) of the up-regulated and 16 (8.04 %) and 49 (24.62 %) of the down-regulated mitoDEGs was prevented with co-exposure to RPV 4µM or 8µM, respectively. In conclusion, alterations in mitochondrial function are implicated in the antifibrogenic action of RPV, pointing to potential novel antifibrotic targets.

Hepatitis B Virus Reactivation after Switch to Cabotegravir/Rilpivirine in Patient with Low Hepatitis B Surface Antibody.

A patient in Japan with HIV began antiretroviral therapy because of acute hepatitis B virus (HBV) 15 years ago, with low hepatitis B surface antibody, and experienced breakthrough HBV reactivation 4 months after switching from bictegravir/emtricitabine/tenofovir alafenamide to cabotegravir/rilpivirine. An immune escape mutation, E164V, was identified in the isolated HBV DNA.

One Year of Long-Acting Cabotegravir and Rilpivirine in People With Human Immunodeficiency Virus and Long Exposure to Antiretroviral Therapy: Data From the SCohoLART Study.

Background: The aim of the study was to evaluate the 12-month cumulative probability of treatment discontinuation (TD) in people with human immunodeficiency virus (HIV; PWH) and a long exposure to antiretroviral therapy (ART) switching to long-acting cabotegravir and rilpivirine (CAB/RPV). Methods: SCohoLART is a single-center, prospective, cohort study designed to collect both samples and clinical data from PWH with virological suppression who switched to bimonthly long-acting CAB/RPV. TD occurred at switch to another regimen for any reason including virological failure (VF); VF was defined as HIV RNA levels ≥50 copies/mL at 2 consecutive measurements or a single HIV RNA level ≥1000 copies/mL. Results were reported as median (interquartile range [IQR]) or frequency (percentage). Cumulative probabilities of TD were estimated using Kaplan-Meier curves. Results: We evaluated 514 participants; 467 (90.9%) were male, and their median age (IQR) was 49 (40-56) years. At the time of switching, the median time from HIV diagnosis and the median duration of ART were 14.0 (IQR, 8.8-20.5) and 11.4 (7.9-17.4) years, respectively; before starting CAB/RPV, the median number of antiretroviral regimens was 3 (2-4). During a median study follow-up (IQR) of 13.1 (9.1-15.5) months, 52 PWH (10.1%) experienced TD, including 4 (0.8%) for VF. The 12-month cumulative probability of TD was 11% (95% confidence interval, 8%-14%). The main cause of TD was injection site reaction (15 participants [28.8%]). Conclusions: The 1-year cumulative probability of TD with long-acting CAB/RPV was quite low in this cohort of people with a median exposure to ART of 10 years, in whom injection site reaction was the leading cause of TD. VFs were rare during study follow-up.

Long-acting injectable ART to advance health equity: a descriptive analysis of US clinic perspectives on barriers, needed support and programme goals for implementation from applications to the ALAI UP Project.

INTRODUCTION: Approval of the first long-acting injectable antiretroviral therapy (LAI ART) medication heralded a new era of HIV treatment. However, the years since approval have been marked by implementation challenges. The "Accelerating Implementation of Multilevel Strategies to Advance Long-Acting Injectable for Underserved Populations (ALAI UP Project)" aims to accelerate the systematic and equitable delivery of LAI ART. METHODS: We coded and analysed implementation barriers according to the Consolidated Framework for Implementation Research (CFIR) domains, desired resources and programme goals from questionnaire short-answer responses by clinics across the United States responding to ALAI UP's solicitation to participate in the project between November 2022 and January 2023. RESULTS: Thirty-eight clinics responded to ALAI UP's solicitation. The characteristics of LAI ART as an innovation (cost, complexity of procurement, dosing interval, limited eligibility) precipitated and interacted with barriers in other CFIR domains. Barriers included obtaining coverage for the cost of medication (27/38 clinics) (outer setting); need for new workflows and staffing (12/38) and/or systems to support injection scheduling/coordination (16/38), transportation and expanded clinic hours (13/38) (inner setting); and patient (10/38) and provider (7/38) education (individuals). To support implementation, applicants sought: technical assistance to develop protocols and workflows (18/38), specifically strategies to address payor challenges (8/38); additional staff for care coordination and benefits navigation (17/38); opportunities to share experiences with other implementing clinics (12/38); patient-facing materials to educate and increase demand (7/38); and support engaging communities (6/38). Clinics' LAI ART programme goals varied. Most prioritized delivering LAI ART to their most marginalized patients struggling to achieve viral suppression on oral therapy, despite awareness that current US Food and Drug Administration approval is only for virally suppressed patients. The goal for LAI ART reach after 1 year of implementation ranged from ≤10% of patients with HIV on LAI ART (17/38) to ≥50% of patients (2/38). CONCLUSIONS: Diverse clinic types are interested in offering LAI ART and most aspire to use LAI ART to support their most vulnerable patients sustain viral suppression. Dedicated resources centred on equity and relevant to context and population are needed to support implementation. Otherwise, the introduction of LAI ART risks exacerbating, not ameliorating, health disparities.

Implementation of long-acting cabotegravir and rilpivirine: primary results from the perspective of staff study participants in the Cabotegravir And Rilpivirine Implementation Study in European Locations.

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. GOV NUMBER: NCT04399551.

Strategic use of salvage long-acting antiretrovirals in the setting of resistance.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. 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.

Efficacy, Safety, and Pharmacokinetics by Body Mass Index Category in Phase 3/3b Long-Acting Cabotegravir Plus Rilpivirine Trials.

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.

Challenges for novel antiretroviral development in an era of widespread TLD availability.

Over 80% of people living with HIV in low-and-middle-income countries (LMICs) take first-line TDF/XTC/DTG (TLD). Due to hard-fought activism, in >100 LMICs TLD now costs under $45pppy under Voluntary License. With final DTG patents expiring by 2029, generic TLD will soon be available globally. We identify seven critical benchmarks underpinning TLDs success which novel ART should now meet, and an eighth for which novel ART should aim. These are superior efficacy; a high genetic barrier to resistance; safety in hepatitis B coinfection; favourable drug-drug interaction profiles including with antimycobacterials; efficacy in HIV-2; safety in pregnancy, long-acting formulation availability and affordable pricing from the outset. We illustrate when generic TLD will become available worldwide and compare this with trial programmes and approval timelines for two case-study novel ART combinations: islatravir/doravirine and cabotegravir/rilpivirine. We demonstrate that currently these regimens and trial programmes will not meet key benchmarks required to compete with TLD.