Bioengineer.org | Archived HIV resistance mutation surfaced years later to undermine long-acting therapy

Bioengineer.org news story

A single case report from Belgium has traced an unusual virological failure of long-acting cabotegravir/rilpivirine therapy back to a resistance mutation that had been silently archived in the patient’s immune cells for nearly three and a half years. The patient, a 41-year-old man with HIV-1 subtype B, met every guideline-based eligibility criterion for the injectable two-drug regimen: years of durable viral suppression, no history of virological failure, a normal body mass index, and injections administered on schedule by certified providers. Yet in January 2024, confirmed virological failure set in, and retrospective sequencing revealed why.

The report, published as a case study in the journal Discover Viruses, describes how next-generation sequencing of proviral DNA from peripheral blood mononuclear cells detected the non-nucleoside reverse transcriptase inhibitor resistance-associated mutation 188L at a frequency of 14.1 percent, roughly 41 months before the patient began long-acting cabotegravir/rilpivirine. That mutation had been absent from baseline plasma genotyping performed years earlier, when the patient was first diagnosed. The finding suggests that resistant variants were either transmitted at the time of infection and later archived, or selected during a brief period of NNRTI-based treatment, and then remained hidden in the viral reservoir until the regimen switch gave them a selective advantage.

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