Dataset Information

Early Experience Implementing Long-Acting Injectable Cabotegravir/Rilpivirine for Human Immunodeficiency Virus-1 Treatment at a Ryan White-Funded Clinic in the US South.

ABSTRACT:

Background

Long-acting injectable (LAI) antiretroviral therapy (ART) has the potential to improve medication adherence, reduce human immunodeficiency virus (HIV) stigma, and promote equity in care outcomes among people with HIV (PWH). We describe our early experience implementing LAI-cabotegravir/rilpivirine (CAB/RPV) for maintenance HIV-1 treatment.

Methods

We launched a pilot LAI-ART program at a large Ryan White-funded clinic in the Southeast, which accept provider-initiated referrals from April 14, 2021 to December 1, 2021. Our interdisciplinary program team (Clinician-Pharmacy-Nursing) verified clinical eligibility and pursued medication access for eligible patients. We describe (1) demographic and clinical variables of PWH referred and enrolled and (2) early outcomes among those accessing LAI-CAB/RPV.

Results

Among 58 referrals, characteristics were median age 39 (Q1-Q3, 30.25-50) years, 74% male, and 81% Black, and payor source distribution was 26% Private, 21% Medicare, 19% Medicaid, and 34% AIDS Drugs Assistance Program. Forty-five patients (78%) met clinical eligibility for LAI-CAB/RPV; ineligibility concerns included evidence of confirmed or possible RPV resistance (n = 8), HIV nonsuppression (n = 3), possible RPV hypersensitivity (n = 1), and pregnancy (n = 1). Among 45 eligible PWH, 39 (87%) enrolled and 15 (38%) initiated LAI-CAB/RPV after a median of 47 (Q1-Q3, 31-95) days since enrollment.

Conclusions

Implementing LAI-ART at a Southern US Ryan White-funded clinic has been challenged by the following: substantial human resource capital to attain drug, administer injections, and support enrolled patients; delayed therapy initiation due to insurance denials; patient ineligibility primarily due to possible RPV resistance; and inability to provide drug regardless of payor source. These barriers may perpetuate disparities in ART access and outcomes among PWH and should be urgently addressed so that LAI-ART can be offered equitably.

SUBMITTER: Collins LF

PROVIDER: S-EPMC9487705 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Early Experience Implementing Long-Acting Injectable Cabotegravir/Rilpivirine for Human Immunodeficiency Virus-1 Treatment at a Ryan White-Funded Clinic in the US South.

Collins Lauren F LF Corbin-Johnson Della D Asrat Meron M Morton Zoey P ZP Dance Kaylin K Condra Alton A Jenkins Kimberly K Todd-Turner Marie M Sumitani Jeri J Smith Bradley L BL Armstrong Wendy S WS Colasanti Jonathan A JA

Open forum infectious diseases 20220902 9

<h4>Background</h4>Long-acting injectable (LAI) antiretroviral therapy (ART) has the potential to improve medication adherence, reduce human immunodeficiency virus (HIV) stigma, and promote equity in care outcomes among people with HIV (PWH). We describe our early experience implementing LAI-cabotegravir/rilpivirine (CAB/RPV) for maintenance HIV-1 treatment.<h4>Methods</h4>We launched a pilot LAI-ART program at a large Ryan White-funded clinic in the Southeast, which accept provider-initiated re ...[more]

PMID: 36147599

Similar Datasets

Project description:BackgroundThe use of a combination of the integrase inhibitor, cabotegravir, and the non-nucleoside reverse transcriptase inhibitor, rilpivirine, in a long-acting injectable form is being considered as an antiretroviral treatment option for people with HIV in sub-Saharan Africa. We aimed to model the effects of injectable cabotegravir-rilpivirine to help to inform its potential effectiveness and cost-effectiveness under different possible policies for its introduction.MethodsWe used an existing individual-based model of HIV to predict the effects of introducing monthly injections of cabotegravir-rilpivirine for people with HIV in low-income settings in sub-Saharan Africa. We evaluated policies in the context of 1000 setting scenarios that reflected characteristics of HIV epidemics and programmes in sub-Saharan Africa. We compared three policies for introduction of injectable cabotegravir-rilpivirine with continued use of dolutegravir-based oral regimens for: all individuals on antiretroviral therapy (ART); individuals with a recently measured viral load of more than 1000 copies per mL (signifying poor adherence to oral drugs, and often associated with drug resistance); and individuals with a recently measured viral load of less than 1000 copies per mL (a group with a lower prevalence of pre-existing drug resistance). We also did cost-effectiveness analysis, taking a health system perspective over a 10 year period, with 3% discounting of disability-adjusted life-years (DALYs) and costs. A cost-effectiveness threshold of US$500 per DALY averted was used to establish if a policy was cost-effective.FindingsIn our model, all policies involving the introduction of injectable cabotegravir-rilpivirine were predicted to lead to an increased proportion of people with HIV on ART, increased viral load suppression, and decreased AIDS-related mortality, with lesser benefits in people with a recently measured viral load of less than 1000 copies per mL. Its introduction is also predicted to lead to increases in resistance to integrase inhibitors and non-nucleoside reverse transcriptase inhibitors if introduced in all people with HIV on ART or in those with a recently measured viral load of less than 1000 copies per mL, but to a lesser extent if introduced in people with more than 1000 copies per mL due to concentration of its use in people less adherent to oral therapy. Consistent with the effect on AIDS-related mortality, all approaches to the introduction of injectable cabotegravir-rilpivirine are predicted to avert DALYs. Assuming a cost of $120 per person per year, use of this regimen in people with a recently measured viral load of more than 1000 copies per mL was borderline cost-effective (median cost per DALY averted across setting scenarios $404). The other approaches considered for its use are unlikely to be cost-effective unless the cost per year of injectable cabotegravir-rilpivirine is considerably reduced.InterpretationOur modelling suggests that injectable cabotegravir-rilpivirine offers potential benefits; however, to be a cost-effective option, its introduction might need to be carefully targeted to individuals with HIV who might otherwise have suboptimal adherence to ART. As data accumulate from trials and implementation studies, such findings can be incorporated into the model to better inform on the full consequences of policy alternatives.FundingBill & Melinda Gates Foundation, including through the HIV Modelling Consortium (OPP1191655).

Project description:IntroductionCabotegravir 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.MethodsEighteen 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.ResultsSeventy 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.ConclusionsCARISEL 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.ClinicaltrialsGov numberNCT04399551.

Project description:BACKGROUND AND OBJECTIVES:Long-acting injectable antiretrovirals represent a pharmacological alternative to oral formulations and an innovative clinical option to address adherence and reduce drug costs. Clinical studies in children and adolescents are characterised by ethical and logistic barriers complicating the identification of dose optimisation. Physiologically-based pharmacokinetic modelling represents a valuable tool to inform dose finding prior to clinical trials. The objective of this study was to simulate potential dosing strategies for existing long-acting injectable depot formulations of cabotegravir and rilpivirine in children and adolescents (aged 3-18 years) using physiologically-based pharmacokinetic modelling. METHODS:Whole-body physiologically-based pharmacokinetic models were developed to represent the anatomical, physiological and molecular processes and age-related changes in children and adolescents through allometric equations. Models were validated for long-acting injectable intramuscular cabotegravir and rilpivirine in adults. Subsequently, the anatomy and physiology of children and adolescents were validated against available literature. The optimal doses of monthly administration of cabotegravir and rilpivirine were identified in children and adolescents, to achieve trough concentrations over the target concentrations derived in a recent efficacy trial of the same formulations. RESULTS:Pharmacokinetic data generated through the physiologically-based pharmacokinetic simulations were similar to observed clinical data in adults. Optimal doses of long-acting injectable antiretrovirals cabotegravir and rilpivirine were predicted using the release rate observed for existing clinical formulations, for different weight groups of children and adolescents. The intramuscular loading dose and maintenance dose of cabotegravir ranged from 200 to 600 mg and from 100 to 250 mg, respectively, and for rilpivirine it ranged from 250 to 550 mg and from 150 to 500 mg, respectively, across various weight groups of children ranging from 15 to 70 kg. CONCLUSIONS:The reported findings represent a rational platform for the identification of suitable dosing strategies and can inform prospective clinical investigation of long-acting injectable formulations in children and adolescents.

Dataset Information

Early Experience Implementing Long-Acting Injectable Cabotegravir/Rilpivirine for Human Immunodeficiency Virus-1 Treatment at a Ryan White-Funded Clinic in the US South.

Background

Methods

Results

Conclusions

Publications

Early Experience Implementing Long-Acting Injectable Cabotegravir/Rilpivirine for Human Immunodeficiency Virus-1 Treatment at a Ryan White-Funded Clinic in the US South.

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