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Genotypic challenges in implementing broadly neutralizing antibody-based long-acting HIV-1 therapies.

Kaiming Tao1, Alon Herschhorn2, Daniela Fera3

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Broadly neutralizing antibodies (bnAbs) show promise for long-acting HIV-1 treatment. Genotypic analysis may help predict resistance, but further research is needed for reliable clinical use.

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Area of Science:

  • Immunology
  • Virology
  • Pharmacology

Background:

  • Broadly neutralizing antibodies (bnAbs) are key for long-acting antiretroviral therapy (ART) in HIV-1 management.
  • bnAbs offer prolonged activity and immune effector functions, advancing long-acting ART options.
  • Current long-acting ART regimens combine bnAbs with small-molecule inhibitors like cabotegravir or lenacapavir.

Purpose of the Study:

  • To review evidence linking HIV-1 Env sequence characteristics to reduced bnAb susceptibility.
  • To assess the potential of genotypic approaches for predicting bnAb resistance in HIV-1.
  • To evaluate the readiness of genotypic methods for clinical application in bnAb-based therapies.

Main Methods:

  • Summarized in vivo selection data from animal models and human studies.
  • Reviewed in vitro selection and susceptibility data.
  • Analyzed evidence linking HIV-1 Env sequence characteristics to bnAb activity.

Main Results:

  • HIV-1 Env sequence characteristics are linked to reduced bnAb susceptibility.
  • In vivo and in vitro studies demonstrate selection for resistant HIV-1 variants.
  • Genotypic analysis can identify resistance in some HIV-1 viruses.

Conclusions:

  • Genotypic analysis of HIV-1 Env shows potential for predicting bnAb resistance.
  • Further research is necessary to validate genotypic methods for clinical use.
  • Accurate assessment of viral susceptibility is crucial for effective bnAb-based HIV-1 therapies.