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Challenges and Opportunities With LA ART
Be Prepared: My Tips for Long-Acting Antiretroviral Therapy Implementation

Released: August 04, 2023

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Key Takeaways
  • To overcome common challenges with administration of long-acting antiretroviral therapy, staff training, a dedicated system for appointments, and preparedness for handling medication logistics are necessary.
  • Future research of long-acting antiretroviral therapy aims to offer less frequent dosing, smaller injections, and self-injection options, as well as improved access.

Before implementing long-acting (LA) antiretroviral therapy (ART) for people living with HIV, numerous practical challenges must be addressed. These issues can be resolved at individual healthcare facilities and without additional burden on patients or the healthcare team.

Injection Administration
One issue with implementing LA ART into clinical practice is injection administration. LA ART must be administered by healthcare professionals, who should be trained on the use of appropriate equipment and gauge/length of the needle depending on the route of administration and size of the patient.

The preferred site for administering SC LA ART is the abdomen, and the preferred site for administering IM LA ART is the ventrogluteal area. Staff at some healthcare facilities may need additional training to properly perform the ventrogluteal IM injection technique.

Another administration issue is ensuring that patients attend the monthly, bimonthly, or every-6-month injection visits. Healthcare facilities should provide adequate resources to help patients adhere to the injection schedule, as well as determine a system for how injection appointments are made and tracked. Many clinics book the next injection appointment at the time of medication administration; other clinics provide the option of choosing an appointment but use a system that notifies the healthcare professional if an appointment is cancelled. Reminder systems for injection appointments also should be considered.

Medication Supply
Another challenge associated with LA ART is timely supply of medications. Healthcare professionals should research appropriate sources of injectable and oral lead-in medications before initiating LA ART. This involves identifying who will provide the medications (eg, on-site pharmacy, general community pharmacy, specialized community pharmacy, direct courier delivery).

The currently available LA ART agents have different refrigeration needs. For example, monthly and bimonthly injectable LA cabotegravir (CAB) plus rilpivirine (RPV) requires the LA RPV to be maintained in cold-chain supply and brought to room temperature prior to administration. However, this medication cannot be re-refrigerated after warming, and medication not used in a timely fashion must be discarded. LA CAB does not require refrigeration but is copackaged in the same box with LA RPV, requiring the entire box to be refrigerated. Biannual LA lenacapavir (LEN) may be stored at room temperature. Logistics of obtaining and administering these medications should be carefully planned.

 Dosing Schedules and Monitoring
The initiation and maintenance dosing schedules for LA ART also can differ. An oral lead-in period is required for LEN and optional for CAB plus RPV.

Monitoring for adverse events and HIV-1 RNA is also important. For both CAB plus RPV and LEN, injection-site reactions (especially pain) are common and typically worse after the first injection but improve with each subsequent injection. After CAB plus RPV is initiated, HIV-1 RNA testing is recommended 4-8 weeks after a switch and after a delay between doses. Drug–drug interactions need to be considered for 9 months after LEN injection because of its long half-life.

Successes With LA ART
Despite these challenges, multiple studies have shown that LA ART can be implemented in groups of patients who are traditionally difficult to treat (eg, those with substance use disorders or living in unstable housing situations).

Bimonthly or biannual visits to a healthcare facility for injections may provide opportunities for physical and mental health screening, collection of health-related quality-of-life assessments, vaccination updates, medication reconciliation, and coordinating receipt of other medications. Although LA ART may increase the number of clinic visits for an individual patient, patients have commented that additional visits are not inconvenient and allow for other health services to be provided. Furthermore, LA ART injection visits potentially could be incorporated with other injectable treatments (eg, coordination with gender-affirming hormone treatment with injectable hormones, injectable opiate substitution, and injectable mental health treatments).

Future Directions
The future of LA ART is promising. Current bimonthly dosing schedules with CAB plus RPV have benefit for travel, such that no oral ART needs be carried across borders, and the longer biannual dosing with LEN paired with a second long-acting injectable agent may extend that benefit even further.

Other studies are exploring alternative ways of delivering LA ART injections, for example, using smaller-volume injections and allowing for self-injection. Indeed, patients have expressed interest in self-injection and likely will embrace new methods of administration.

Finally, some healthcare professionals have voiced concerns that increased access to treatments in resource-limited settings is important to address. Future treatment options currently in research, many of which involve nonoral options, will need to offer flexibility and availability and be adapted to real-world clinical settings.

Your Thoughts?
What future opportunities with LA ART interest you most? Join the conversation by adding a comment.