Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals

SPARTAC Trial Investigators, Trial Steering Committee (TSC), Data and Safety Monitoring Committee (DSMC), Clinical Endpoint Review Committee

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Advances in immunoglobulin (Ig) sequencing technology are leading to new perspectives on immune system dynamics. Much research in this nascent field has focused on resolving immune responses to viral infection. However, the dynamics of B-cell diversity in early HIV infection, and in response to antiretroviral therapy, are still poorly understood. Here, we investigate these dynamics through bulk Ig sequencing of samples collected over 2 years from a group of eight HIV-1 infected patients, five of whom received antiretroviral therapy during the first half of the study period. We applied previously published methods for visualizing and quantifying B-cell sequence diversity, including the Gini index, and compared their efficacy to alternative measures. While we found significantly greater clonal structure in HIVinfected patients versus healthy controls, within HIV patients, we observed no significant relationships between statistics of B-cell clonal expansion and clinical variables such as viral load and CD4+ count. Although there are many potential explanations for this,we suggest that important factors include poor sampling resolution and complex B-cell dynamics that are difficult to summarize using simple summary statistics. Importantly,we find a significant association between observed Gini indices and sequencing read depth, andwe conclude that more robust analytical methods and a closer integration of experimental and theoretical work is needed to further our understanding of B-cell repertoire diversity during viral infection.

Original languageEnglish
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Issue number1676
StatePublished - Jul 20 2015


  • B-cell receptor
  • Diversity
  • Gini index


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