Case analyses examine loss of virologic suppression on injectable HIV treatment in the Netherlands

Rare occurrences of emergent HIV viremia while on injectable cabotegravir/rilpivirine treatment may be associated with the development of extensive resistance mutations to two common drug classes, case reports from the Netherlands showed. Their exploration of five patients revealed low drug levels and extensive resistance in all cases.

About This Study

“Virological failure after switch to long-acting cabotegravir and rilpivirine injectable therapy: an in-depth analysis” was published online on Jan, 11, 2024, in Clinical Infectious Diseases. The lead author is Berend J. van Welzen, M.D., Ph.D., of the Department of Infectious Diseases at University Medical Center Utrecht, the Netherlands.

Key Research Findings

This in-depth analysis of virological failures on long-acting injectable cabotegravir/rilpivirine in five people living with HIV in the Netherlands found low drug levels and extensive drug-resistance mutations after a detectable viremia was confirmed. Participants included one trans- and one cisgender woman and three cisgender men, all between 38 and 56 years old. Three of the five cases of virologic failure had no known risk factors at baseline, while the remaining two had only high body mass index.

At baseline, all participants were virally suppressed, without a history of viral failure or current hepatitis B, and their virus was tested for reverse transcriptase-associated mutations. No testing for integrase inhibitor-associated mutations was performed. Four participants had an oral lead-in phase, while one participant started injectable cabotegravir/rilpivirine immediately.

After 3-13.5 months on injections, viral load increased to >50 copies/mL for each of these five individuals. When viral failure was confirmed, four of five participants were switched to oral treatment regimens (one declined). At that point, HIV in all participants was resistant to non-nucleoside reverse transcriptase inhibitors and in four participants was resistant to integrase strand transfer inhibitors.

In one participant, needle length was not adjusted despite her body mass index increasing to 33.5 kg/m². Pharmacokinetic testing showed low rilpivirine levels. On a new treatment regimen, she re-suppressed within three months. The second and third participants had low cabotegravir levels and re-suppressed within six and seven months, respectively, on new regimens. The fourth participant had low levels of both cabotegravir and rilpivirine. He, too, re-suppressed on different HIV drugs. The fifth participant received her third injection series late, did not have oral bridging, and declined a switch to oral treatment after virologic failure was confirmed.

Discussion Highlights and Implications for Practice

The researchers suggested that in two participants, low drug levels were likely due to insufficient needle length or a delayed injection, and in one case problems with the cabotegravir injection were also possible.

Clinicians need to continue monitoring for potential risk factors during injectable treatment, especially since virologic failure may confer resistance to both integrase and reverse transcriptase inhibitors, the authors said. Future studies should also look at strategies to limit the loss of antiretroviral therapy options in this situation, they concluded.

SEE ALSO:

• HIV i-Base: Five cases of viral failure on CAB-LA and RPV-LA injections