Comparison of Four NGS Platforms for HIV-1 Coreceptor Tropism Prediction

What is it about?

This study compared the ability of four next-generation sequencing (NGS) platforms to detect HIV-1 coreceptor usage, which is important for determining treatment with CCR5 antagonists. The V3 region of the HIV-1 env gene was sequenced using 454 TM, PacBioH, IlluminaH, and Ion Torrent TM platforms. Cross-platform variation was evaluated, and HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule. Error rates related to indels and nucleotide substitutions were low. All NGS platforms detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used), compared to Trofile (80%) and population sequencing (70%). These findings suggest that any NGS-based method can be used to predict HIV-1 coreceptor usage, which could lead to more affordable and accessible tests for treatment with CCR5 antagonists.

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Why is it important?

This study is important because it evaluates the ability of different Next-Generation Sequencing (NGS) platforms to predict HIV-1 coreceptor tropism, which is crucial for determining the efficacy of CCR5 antagonists in antiretroviral therapy. This information can help optimize treatment strategies and improve patient outcomes. Key Takeaways: 1. All four NGS platforms (454 TM, IlluminaH, PacBioH, and Ion Torrent TM) can effectively detect minority non-R5 variants, making any NGS-based method a viable option for predicting HIV-1 coreceptor usage. 2. The V3 region of the HIV-1 env gene was sequenced using the 454 TM, PacBioH, IlluminaH, and Ion Torrent TM platforms, and cross-platform variations were found to be low compared to the actual HIV-1 sequence variation. 3. The NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used), compared to Trofile (80%) and population sequencing (70%).