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Weekly ISL Plus LEN Australia
Once-Weekly Oral ISL Plus LEN for HIV Treatment: Australian Perspective

Released: April 03, 2024

Expiration: April 02, 2025

Andrew Carr
Andrew Carr, DSc, MD, MBBS, FRACP, FRCPA
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Key Takeaways
  • Although minimizing the impact of HIV treatment on daily life is a priority for people living with HIV in Australia, injectable antiretroviral therapy has not been widely adopted because of the increase in yearly clinic visits and inability to self-administer.
  • Interim results of an open label, phase II study of once-weekly oral islatravir plus lenacapavir demonstrated efficacy and tolerability.

In Australia, universal government-funded antiretroviral therapy (ART) has made AIDS largely an illness of the past. The rate of new AIDS diagnoses per year peaked at approximately 1000 in 1994 and declined rapidly after widespread implementation of effective ART. Indeed, AIDS is no longer a notifiable disease to Australian health authorities. Furthermore, the test and treat approach, as well as pre-exposure prophylaxis implementation, have reduced the incidence of new HIV infections since 2012, although “only” by approximately 50%.

In 2022, the Australian HIV care cascade was 91-92-98, meaning that 91% of people living with HIV received a diagnosis, 92% of those diagnosed were receiving ART, and 98% of those receiving ART were virologically suppressed. For those receiving the standard-of-care ART regimen (ie, once-daily integrase inhibitor–based single tablet regimens [STRs]), it is hard to improve on this high rate of virologic suppression. Follow-up care is also simple: Most treated people only need to come in to check their viral load and undergo clinical assessment once every 6 months, some only every 12 months.

Refocusing HIV Care in Australia
Therefore, improving HIV care in Australia is now focused on minimizing the impact of HIV and ART on day-to-day life. Assuming all new approved regimens are effective, safe, and free, most people living with HIV want simpler, self-administered, painless medicine. They also want to reduce the need to take time off work and lower healthcare costs with fewer clinic visits. Treatments taken less frequently than once a day are of great interest.

Injectable cabotegravir plus rilpivirine, the first nondaily ART regimen, is effective, but has not been widely adopted in Australia because it requires at least 6 clinic visits per year (rather than 1 or 2) for administration in a healthcare setting and administration can be painful. Next-generation injectables will undoubtedly improve upon these shortcomings. 

Weekly Oral Islatravir Plus Lenacapavir
Another possible alternative to daily oral ART to improve health-related quality of life is still in the form of a single pill, but taken less frequently. A welcomed study by Colson and colleagues, presented at CROI 2024, reported the results of a phase II trial of once-weekly oral islatravir (ISL) + lenacapavir (LEN) in a single pill.

In this open-label study, patients living with HIV with virologic suppression on daily bictegravir/emtricitabine/tenofovir alafenamide were randomized to continue this regimen or switch to weekly oral ISL + LEN (2 mg/300 mg) for 48 weeks. The results are perhaps as good as one could hope for in a phase II trial at Week 24. Only 1 patient who switched to weekly oral ISL + LEN experienced low-level virologic failure but was viremic at baseline and resuppressed at Week 30 without a change in regimen. There were no discontinuations because of treatment-related adverse events.

More Data Needed
So, what ISL + LEN data do we still need? We cannot establish noninferiority or make definitive conclusions about safety—specifically, any effect of this dose of ISL on CD4+ cell and total lymphocyte counts—based on results from the phase II trial. Previous studies have shown numerically higher rates of lymphocyte count decreases among participants receiving ISL, albeit on a higher dose. A much larger phase III trial of ISL + LEN will hopefully begin later in 2024. The generalizability of the results to come from this phase III trial will depend on the population enrolled.

Adherence Evaluation Will Be Key
In addition, a weekly oral regimen may come with unforeseen consequences including dosing fatigue and adherence challenges. Despite a weekly regimen being an improvement over a daily one for many people, some people may prefer an even less frequent option in the form of an injectable, despite it requiring more office visits and possibly causing injection site pain.

Will patients become lax in taking a pill on time, every time, if it is not part of their daily routine? Personally, I will be more convinced of the sustained efficacy of weekly oral dosing when I see the adherence data through Week 96.

To me, it seems likely that the era of once-daily STRs is coming to an end for many people living with HIV in Australia who may be able to soon choose from several weekly (or even less frequent) STRs or painless, self-administered second-generation injectables.

Your Thoughts?
What advancements in HIV treatment are most important to your patients? Leave a comment to join the discussion.