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HIV-1 neutralizing antibody response and viral genetic diversity characterized with next generation sequencing.

  • Author(s): Carter, Christoph C
  • Wagner, Gabriel A
  • Hightower, George K
  • Caballero, Gemma
  • Phung, Pham
  • Richman, Douglas D
  • Pond, Sergei L Kosakovsky
  • Smith, Davey M
  • et al.
Abstract

To better understand the dynamics of HIV-specific neutralizing antibody (NAb), we examined associations between viral genetic diversity and the NAb response against a multi-subtype panel of heterologous viruses in a well-characterized, therapy-naïve primary infection cohort. Using next generation sequencing (NGS), we computed sequence-based measures of diversity within HIV-1 env, gag and pol, and compared them to NAb breadth and potency as calculated by a neutralization score. Contemporaneous env diversity and the neutralization score were positively correlated (p=0.0033), as were the neutralization score and estimated duration of infection (EDI) (p=0.0038), and env diversity and EDI (p=0.0005). Neither early env diversity nor baseline viral load correlated with future NAb breadth and potency (p>0.05). Taken together, it is unlikely that neutralizing capability in our cohort was conditioned on viral diversity, but rather that env evolution was driven by the level of NAb selective pressure.

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