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Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
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First Case of HIV Seroconversion With Integrase Resistance Mutations on Long-Acting Cabotegravir for Prevention in
Catherine A Koss1, Monica Gandhi1, Elias K Halvas2
1University of California, San Francisco, San Francisco, California, USA.
Open Forum Infectious Diseases
|September 4, 2024
Summary
Long-acting cabotegravir (CAB-LA) is effective for HIV prevention. This case shows INSTI resistance developing on CAB-LA, highlighting the need for faster HIV testing and continuous access to prevention methods.
Area of Science:
- Infectious Diseases
- Virology
- Pharmacology
Background:
- Long-acting cabotegravir (CAB-LA) is a highly effective pre-exposure prophylaxis (PrEP) for HIV prevention.
- Clinical trials have noted delayed HIV diagnoses and integrase strand transfer inhibitor (INSTI) resistance in individuals using CAB-LA.
- This report details the first documented case of HIV infection with INSTI resistance occurring during routine clinical use of CAB-LA.
Purpose of the Study:
- To report the first case of HIV infection with integrase strand transfer inhibitor (INSTI) resistance in a patient receiving long-acting cabotegravir (CAB-LA) in routine clinical care.
- To investigate the diagnostic challenges, antiretroviral drug levels, and resistance patterns associated with HIV acquisition during CAB-LA use.
Main Methods:
- The SeroPrEP study enrolled individuals in the US who acquired HIV while on PrEP.
- Resistance mutations in full-length HIV-1 integrase were identified using single-genome sequencing (SGS).
- Plasma and hair cabotegravir concentrations were quantified using liquid chromatography-tandem mass spectrometry.
Main Results:
- A 23-year-old individual developed HIV infection with INSTI resistance (Q148R mutation) after restarting CAB-LA, despite a 20-day gap between HIV testing and injection.
- Sensitive research assays detected cabotegravir resistance, while commercial genotyping failed.
- High plasma cabotegravir levels were observed post-diagnosis, indicating adherence, but resistance emerged.
Conclusions:
- This case underscores the importance of sensitive assays for detecting INSTI resistance in patients on CAB-LA.
- Accelerated pathways for HIV testing and CAB-LA initiation are crucial to optimize acute HIV detection and minimize resistance risk.
- Ensuring continuous access to CAB-LA, irrespective of insurance status, is vital for reducing HIV infections in this population.
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