Role of HIV Minority Variants in Drug Resistance

What is it about?

A novel HIV-1 genotyping and coreceptor tropism assay based on deep sequencing (DEEPGEN) was used to analyze the presence of minority variants carrying mutations associated with reduced susceptibility to protease (PR), reverse transcriptase (RT), and integrase strand transfer integrase inhibitors (INSTIs), as well as HIV-1 coreceptor tropism in twelve heavily treatment-experienced patients. The study found that these low-abundance HIV-1 variants were associated with drug susceptibility, replicative fitness, and coreceptor tropism determined using sensitive phenotypic assays, enhancing the overall burden of resistance to all four antiretroviral drug classes. The presence of these minority drug-resistant variants may have an impact on treatment outcome, and further studies are needed to clarify their potential significance in clinical practice.

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Why is it important?

The research is important because it sheds light on the role of minority HIV-1 drug-resistant variants in patients experiencing virologic failure, particularly in those treated with antiretroviral therapy. Understanding the impact of these minority variants can help in determining the overall burden of resistance to different antiretroviral drug classes and may have implications for the clinical management of HIV infections. Key Takeaways: 1. The study used a novel HIV-1 genotyping and coreceptor tropism assay based on deep sequencing (DEEPGEN) to analyze minority HIV-1 drug-resistant variants in patients experiencing virologic failure. 2. The presence of these low-abundance HIV-1 variants was associated with drug susceptibility, replicative fitness, and coreceptor tropism, enhancing the overall burden of resistance to all four antiretroviral drug classes. 3. The accumulation of primary drug-resistance mutations appears to have a negative effect on overall viral replication, as demonstrated by the negative correlation between plasma viral load and the level of HIV-1 drug resistance determined by deep sequencing. 4. Further longitudinal studies based on deep sequencing tests are needed to better understand the clinical relevance of these minority HIV-1 variants and their potential impact on antiretroviral therapy.