Treatment of Acquired Immunodeficiency Syndrome When Dolutegravir Plus TXF/XTC Has Failed
Clinical Scenario
This protocol addresses patients with HIV/AIDS who have experienced virologic failure on a dolutegravir-based regimen. Accumulation of extensive multiclass resistance — including to integrase strand transfer inhibitors — places these patients beyond the reach of standard second-line options and calls for a structured next-line approach.
Previous Treatment — Failure Condition
The prior regimen — dolutegravir plus TXF/XTC (initiated after HIV reverse transcriptase–protease and integrase genotyping) — did not achieve the target of HIV RNA below 50 copies/mL. Persistent viremia in the setting of multiclass resistance is the trigger for escalation to this protocol.
Next-Line Approach — Partial Overview
This protocol turns to agents operating through novel mechanisms of action — distinct from the classes that have already failed — with the regimen structured to include at least two fully active components. Existing NRTI backbone therapy continues to contribute alongside these newer agents.
The full agent selection, combination strategy, and management algorithm are available in the complete protocol →
Treatment Goal
Achieve virologic suppression to HIV RNA below 200 copies/mL.
References
DOI: 10.1001/jama.2024.24543
- In individuals with virologic failure with extensive multiclass resistance (including to InSTIs), agents with novel mechanisms of action such as ibalizumab, fostemsavir, or lenacapavir are recommended, ideally in combination to allow for 2 fully active drugs (evidence rating: AIa).
- Also, continued treatment with NRTIs such as TXF/XTC is recommended, since they retain partial activity even in the presence of extensive resistance mutations (evidence rating: AIIa).
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