Brave Approach: biktarvy as a Viable Switch for Cabotegravir/Rilpivirine Failure

Clinicians Explore Novel Strategy⁢ Amidst Growing ⁤Need for Backup Regimens

In a bold move that challenges conventional treatment guidelines, clinicians are exploring the use of bictegravir-based regimens as a potential switch for patients experiencing virologic failure on long-acting injectable cabotegravir/rilpivirine (CAB/RPV). This innovative approach, born out of necessity adn early promising results, aims ⁢to provide a much-needed backup option for individuals who develop resistance to⁤ the injectable therapy.

The Case of Patient Zero: A turning Point

The impetus for this exploration began wiht a patient who, after initiating CAB/RPV, experienced virologic failure.Despite having a history of integrase inhibitor resistance mutations, specifically at position 138, the decision was made⁢ to switch⁤ her to a bictegravir-based regimen.This choice was notably noteworthy as bictegravir,a second-generation integrase inhibitor,is not typically recommended in cases with pre-existing integrase resistance.

“What would be the motivation to change therapy in a patient who is currently on a simple regimen that is working?” asked Dr.Jean-Pierre Giguère, a key figure in this observational study. The⁢ decision was made to continue with the‍ bictegravir regimen, closely ⁢monitoring the patient⁣ to ensure viral suppression. This initial success, termed the “n of one experience,”⁤ marked the beginning of a small but meaningful observational cohort.

Expanding the Cohort: From‍ One to Six

Following the initial success, the ⁢clinical team expanded their approach to include⁣ the next five patients ‍who⁤ experienced virologic failure on CAB/RPV at their hospital. The ⁤decision to continue with⁣ bictegravir was based on the positive⁢ outcome of the first patient,effectively growing the observational data to an “n of six.”

A critical observation within this expanded group was ⁢the⁢ presence of mutations at both positions 138 and 148 in three of the patients. While these mutations are ⁣known to confer significant loss of susceptibility to cabotegravir,their impact on bictegravir susceptibility was less understood,with limited clinical data available. “From an in vitro perspective, you would not suspect that these ⁣mutations would much impact bictegravir susceptibility,” Dr. Giguère noted. “But what has been lacking⁢ has been clinical data.”

Expert Perspectives: Brave but‍ Cautious

The strategy has been described as “brave” ‍by Dr. laura Waters, a ⁤consultant physician in sexual health and HIV medicine.she highlighted that while other cases of switching to integrase inhibitors‍ after CAB/RPV failure have been reported, they generally did⁤ not involve patients with pre-existing integrase inhibitor resistance mutations.

“As we’re learning more and more, resistance isn’t absolute, and both our second-generation integrase inhibitors have high inhibitory quotients, and so we would ⁤expect that virologic suppression would be possible for many individuals,”⁣ Dr. Waters commented.

However, she also raised concerns about ⁣the durability of the response. With follow-up periods for some ⁣patients being less than a year, and the longest at 20 months, questions remain about the ⁣long-term efficacy. “The concern is around forgiveness: What happens if somebody misses a dose? What happens if somebody takes a cation-containing treatment or⁢ supplement that reduces integrase concentrations further?” ⁤she pondered.

The Need for a Simple, Tolerated Backup

Dr. Giguère emphasized the importance‍ of establishing a safe and effective backup regimen for patients who experience virologic failure on CAB/RPV. ⁣”I think we have to be able to come up with a simple, well-tolerated backup regimen ⁤in the case of ⁣failure,” he stated.

While the bictegravir-based regimen is still under investigation, the early findings offer a glimmer of hope.⁤ Dr. giguère encourages‍ other clinicians to replicate this⁣ experience to gather more data.”Time will tell if⁤ the effect is long-lasting,⁤ and ⁢we need more people to confirm it,” he concluded.

The study received no external funding, and Dr. Giguère reported no relevant financial relationships. Dr. Waters has received speaker and advisory fees from Merck ⁣Sharp & Dohme (MSD), ViiV Healthcare, Janssen Pharmaceuticals, and AbbVie, and is⁢ an investigator on trials funded by Gilead Sciences, MSD, and ViiV ⁢Healthcare.