BHIVA interim guidance on long-acting cabotegravir and rilpivirine injections

On 7 February 2022, BHIVA published interim guidance on long-acting cabotegravir and rilpivirine injections (CAB/RPV-LA). [1]

This is ahead of the expected update to the full ART guidelines that are due to be published in April.

As with the EU indication this will limit access to people who have had undetectable viral load for more than six months on their current ART. This includes having no history of viral failure or drug resistance to INSTIs or NNRTIs.

Unlike previous BHIVA guidance, it also includes and an editorial criteria for potential recipients to agree to a specified risk of viral failure, despite good adherence.

People currently using this treatment in a study or on expanded access can continue.

Viral load monitoring is recommended with every two-monthly dose. This should be immediately repeated if results become detectable.

Nine recommendations for new use of CAB/RPV-LA

Have a significant need for injectable antiretroviral therapy (ART); and
Have been virally suppressed to <50 copies/mL for at least 6 months; and
Have no known or suspected non-nucleoside reverse transcriptase inhibitor (NNRTI) or integrase inhibitor (INSTI) resistance; and
Have no history of virological failure or unplanned treatment interruption on NNRTI- or INSTI-containing ART; and
Have no history of INSTI monotherapy; and
Can tolerate and commit to 2-monthly attendance for injections; and
Accept the risk of virological failure despite complete adherence (approximately 1 in 70 at year 1 and 1 in 60 at year 2); and
Have a BMI <30 kg/m² AND non-A1/6 subtype if baseline resistance is unavailable; and
Do not need a tenofovir-containing regimen for the treatment or prevention of hepatitis B.

Continuing CAB/RPV-LA

Have received LA-CAB/RPV in a clinical trial
Are on LA-CAB/RPV as part of a compassionate access or named patient programme

Recommended monitoring

HIV-RNA quantification at every visit
Prompt recall for repeat testing and resistance testing if viral rebound occurs

comment

These guidelines are important and are a temporary document until the full treatment guidelines are updated and published at the BHIVA spring conference in April.

This is the first time that BHIVA have actively included a recommendation that involves people having to agree to an awareness of potential risks, which should really be included for every drug.

However, the mechanism to explain drug resistance in some participants, despite perfect adherence, has not been explained.

In a predictive model, viral failure has been associated with having two or more of the following four factors: (i) BMI >30; (ii) low RPV levels at week 8; (iii) baseline mutations to RPV; and (iv) the A1 or A6 HIV subtype (common in Russia). Of these, low RPV levels and baseline mutations are easiest to monitor and explain, as they would results in periods of effective cabotegravir monotherapy.

Potential differences in interpatient PK related to injection technique might also be related. [2]

References