Implementing Injectables

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A syringe is being filled from a vial.

Considerations for Cabotegravir-Rilpivirine Long-Acting Therapy

Long-acting cabotegravir and rilpivirine injections are approved in Canada, Europe, and the United States.1 The unique pharmacokinetic and pharmacodynamics properties of long-acting cabotegravir and rilpivirine injectables allow them to be administered once monthly2; the most prominent of these are long elimination half-lives with intramuscular administration (cabotegravir = 5.6-11.5 weeks and rilpivirine = 13-28 weeks).1

The drug–drug interaction profile of the injectable and oral formulations are different; each formulation should be checked for interactions before initiation of therapy. The 96-week results of the FLAIR study mirrored the 48-week data showing that this regimen was noninferior to the standard of care for maintaining viral suppression.3 In addition, 256-week data from the LATTE-2 trial demonstrated long-term efficacy, tolerability, and durability of long-acting cabotegravir-rilpivirine (Cabenuva, ViiV Healthcare) injection therapy.4

Virologic control is entwined with quality of life.5 There is the potential for once-monthly injectable agents to improve quality of life by incorporating patient treatment preferences and removing stigma-related concerns. In a survey of 688 people with HIV, almost two-thirds were interested in long-acting injectable therapy.5 Most of these respondents noted that injectable treatment would fulfill an unmet need, such as suboptimal adherence, confidentiality concerns, and the emotional burden of daily dosing.

Physicians noted different levels of likelihood to recommend injectable therapy depending on individual patient factors.5 They were more likely to offer injectable therapy in cases of dysphagia or malabsorption. However, the majority would also recommend this treatment strategy for suboptimal adherence.5 Of note, these data were collected before drug approval and evaluated as an every 2-month dosing regimen. Benefits that were perceived with injectable therapy included being able to travel without worrying about forgetting medication. Physicians noted that there would be increased patient contact (once monthly) compared with a lower frequency of encounters.5

Data are also available for an every 2-month dosing regimen.6 Patient satisfaction data collected during treatment indicate that an every 8-week regimen is preferred over an every 4-week regimen; however, patient satisfaction scores were high for both dosing regimens.7 In addition, approximately 80% of respondents noted that local injection site reactions were acceptable after 48 weeks of therapy.

Implementation

Opportunities exist with injectable agents to improve adherence and outcomes, including less frequent dosing, avoidance of pill fatigue and HIV-related stigma, and decreased pill burden.8 However, the requirement of an oral lead-in and management of missed doses present barriers to treatment initiation.

Implementation concerns to be considered include workflow, procurement, reimbursement, and nonadherence.9 Operationally, a multidisciplinary group should form a clinic-specific protocol and outline each identification, initiation, and maintenance process step. Health care professional training also may be necessary because the Z-track injections cannot be self-administered.9

Refrigerated storage and availability of examination rooms for injection also should be considered.9 At least 15 minutes are needed for the vials to be allowed to come to room temperature before injection. A 10-minute observation period also is recommended post-injection. Overall, this represents at least a 30-minute appointment.9

From a payment standpoint, the medication may be covered by either pharmacy or medical benefits. A full investigation and precertification or prior authorization should be completed to ensure the exact cost is known before initiating therapy. Financial assistance and benefits investigation can be facilitated through the ViiV Connect Portal (https://bit.ly/306wEsm-IDSE).9 The oral lead-in of both medications is available through TheraCom, LLC Specialty Pharmacy at no cost.9Appointments for injections should be easily distinguished from other types of clinic visits. This will allow identification of missed or canceled appointments for injections to perform outreach as soon as possible for rescheduling. Delayed or missed doses should be addressed immediately.8

A screening process should be considered to identify people for injectable therapy appropriately. Many people initiating injectable therapy will increase their number of clinic visits per year, raising other issues such as parking fees or the need for time off work. Transportation also should be addressed.9 Patients should immediately report any changes in insurance status to ensure an uninterrupted supply of medication.

Implementation strategies for an every 8-week regimen will differ slightly from every an 4-week regimen. Direct-to-injection (no oral lead-in) data are available; however, this is not yet an approved strategy.8 In addition, attending an injection appointment 6 times per year versus 12 times per year may allow a larger population to initiate therapy. These data support the need to offer injectable therapy to patients with an appropriate indication, as it is challenging to predict confidentiality concerns or emotional burdens. The overall interest of people with HIV to use injectables is an essential piece of data to allow clinicians to allocate appropriate resources.

This article was originally written by Milena Murray, PharmD, MSc, BCIDP, AAHIVP, FCCP and published in 'Infectious Disease Special Edition. Read the original article here

References

  1. Hodge D, Back DJ, Gibbons S, et al. Pharmacokinetics and drug-drug interactions of long-acting intramuscular cabotegravir and rilpivirine. Clin Pharmacokinet. 2021;60(7):835-853.
  2. Podany AT, Scarsi KK, Pham MM, et al. Comparative clinical pharmacokinetics and pharmacodynamics of HIV-integrase strand transfer inhibitors: an updated review. Clin Pharmacokinet. 2020;59(9):1085-1107.
  3. Orkin C, Oka S, Philibert P, et al. Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study. Lancet HIV.2021;8:e185-e196.
  4. Smith GHR, Henry WK, Podzamczer D, et al. Efficacy, safety, and durability of long-acting cabotegravir and rilpivirine in adults with human immunodeficiency virus type 1 infection: 5-year results from the LATTE-2 study. Open Forum Infect Dis. 2021;8:ofab439.
  5. Akinwunmi B, Buchenberger D, Scherzer J, et al. Factors associated with interest in a long-acting HIV regimen: perspectives of people living with HIV and healthcare providers in four European countries. Sex Transm Infect. Published online February 25, 2021. http:doi://dx.doi.org/10.1136/sextrans-2020-054648
  6. Swindells S, Lutz T, van Zyl L, et al. Long-acting cabotegravir + rilpivirine for HIV-1 treatment: ATLAS week 96 results. AIDS. Publsihed online July 13, 2021. http:doi://dx.doi.org/10.1097/qad.0000000000003025
  7. Chounta V, Overton ET, Mills A, et al. Patient-reported outcomes through 1 year of an HIV-1 clinical trial evaluating long-acting cabotegravir and rilpivirine administered every 4 or 8 weeks (ATLAS-2m). Patient. 2021;14(6):849-862.
  8. Scarsi KK, Swindells S. The promise of improved adherence with long-acting antiretroviral therapy: what are the data? J Int Assoc Provid AIDS Care. 2021;20:23259582211009011.
  9. Howe ZW, Norman S, Lueken AF, et al. Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic. Pharmacotherapy.2021;41:686-699.

 

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