Treatment of Acquired Immunodeficiency Syndrome When Integrase Strand Transfer Inhibitor Resistance Is Suspected — With Prior Long-Acting Cabotegravir PrEP Exposure
This protocol covers the management of AIDS in a specific clinical situation: patients presenting with suspected integrase strand transfer inhibitor (InSTI) resistance, particularly those with prior exposure to long-acting cabotegravir (CAB-LA) as pre-exposure prophylaxis.
Clinical Scenario
Prior exposure to long-acting cabotegravir as PrEP raises a significant concern for InSTI resistance at the time of HIV diagnosis or virologic failure. Resistance testing results are often not immediately available, making empiric regimen selection critical to avoid administering a regimen compromised by pre-existing resistance.
Treatment Approach
When InSTI resistance is suspected — especially in the context of prior CAB-LA PrEP — initial therapy is anchored to a boosted protease inhibitor-based approach rather than an integrase inhibitor. Once resistance testing results become available, the regimen may be reconsidered based on the findings.
The specific agents, sequencing, and conditions for modification are detailed in the full structured protocol.
References
DOI: 10.1001/jama.2024.24543
- Initial boosted darunavir (DRV)–containing regimens are recommended when InSTI resistance is suspected before the results of resistance testing are returned, particularly when there has been prior exposure to long-acting cabotegravir (CAB-LA) as PrEP (evidence rating: AIIb).
- If therapy is desired before genotype results are available or if InSTI resistance is present or suspected, ritonavir- or cobicistat-boosted darunavir and TXF/XTC should be used (evidence rating: AIIb).
- The treatment can be modified to an InSTI or nonnucleoside reverse transcriptase inhibitor (NNRTI)–based therapy once results of the test excludes resistance to these drug classes.
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