What is it about?
Dolutegravir (DTG) has been a game-changer in HIV treatment, especially in low-resource settings, due to its effectiveness and safety. However, recent studies have raised concerns about the emergence of resistance to DTG in patients who have never been treated with integrase strand transfer inhibitors (INSTIs) before. A systematic review analyzed data from 21 studies involving 59 patients who experienced virological failure while on a DTG-based regimen. The most common resistance mutations found were G118R and R263K. G118R, especially when combined with other mutations like T66I and E138K, led to high-level resistance to all INSTIs. R263K also caused resistance but to a lesser extent. These findings highlight the importance of monitoring resistance patterns, particularly in non-HIV-B subtypes, to optimize treatment strategies and ensure the effectiveness of DTG-based therapies. The emergence of these resistance mutations is particularly concerning in resource-limited settings where DTG is commonly used without baseline resistance testing.
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Why is it important?
Monitoring resistance patterns in HIV treatment is crucial because it helps optimize antiretroviral therapy (ART) strategies and ensures the continued effectiveness of drugs like Dolutegravir (DTG). This is especially important in resource-limited settings where baseline resistance testing is often not available. By understanding and tracking resistance mutations, healthcare providers can adapt treatment plans to prevent virological failure and the spread of drug-resistant HIV strains.
Perspectives
The emergence of resistance to Dolutegravir (DTG) is a significant concern for the global fight against HIV. DTG has been a cornerstone of HIV treatment due to its high efficacy and low side-effect profile. However, the development of resistance mutations like G118R and R263K threatens to undermine the progress made in HIV treatment. This is especially critical in low-resource settings where alternative treatment options may be limited.
Dr. Nishant Raman
Read the Original
This page is a summary of: Worrisome Emergence of Pan-INSTI Resistance: A Systematic Scoping Review of Dolutegravir Resistance in INSTI-Naïve Patients Post-Therapy Failure, February 2025, Cold Spring Harbor Laboratory Press,
DOI: 10.1101/2025.02.01.25320414.
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