Five cases of viral failure on CAB-LA and RPV-LA injections

15 January 2024. Related: Antiretrovirals, Drug resistance.

Simon Collins, HIV i-Base

Five cases of unexpected viral failure after switching to long-acting injectable ART were reported as a case series from the Netherlands, none of whom had high predicted risk of failure. 

Extensive NNRTI-associated mutations were reported in 5/5 cases and INSTI-associated mutations were reported in 4/5.

All cases had low drug levels of either one or both drugs, likely linked to the failing ART. All injections were given by trained health workers within the recommended dosing window.

Three cases had plausible explanations for viral failure and two didn’t.

• One person found to have very low rilpivirine drug levels had rapidly put on weight after switching to CAB-LA/RPV-LA. BMI increased from 29.0 to 35.5 kg/m² but the recommendation to use a longer injection needle hadn’t been followed.
• One case with unexplained low drugs levels of both drugs.
• One case with unexplained low CAB drug levels.
• A case where low-level viral rebound to 260 copies/mL was not investigated which two months later increased to 610,000. Retrospective testing of earlier samples showed unexplained low levels of both drugs.
• The final case was more complicated for having a high BMI (45.5 kg/m²) – but the recommended longer needle was used – and because fewer samples were available. However, one of the sets of injections had been after 11 weeks rather than 8, without oral bridging dosing. Retrospective testing showed low drug levels in samples that were available.

In clinical studies, the risk of viral rebound in the context of good adherence is about 1.2% a year.

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The paper discusses the impact of extensive drug resistance in these cases, intra- and inter-patient variability in drug levels and the lack of consistency in studies looking at the role of high BMI in increasing the risk of viral failure.

Given that low drug levels are implicated in these and other reported cases of viral failure the authors also suggest the possible role of an early drug level test at week 8 after switching to this injectable combination, when both drugs will be at steady state.

van Welzen BJ et al, Virological failure after switch to long-acting cabotegravir and rilpivirine injectable therapy: an in-depth analysis, Clinical Infectious Diseases, 2024; ciae016. (11 Jan 2024)
https://doi.org/10.1093/cid/ciae016