Lifelong adherence to once-daily (QD) HIV therapy remains a challenge for many patients. Extended duration dosing with forgiving agents is a potential means to address this issue. Towards this goal, we targeted the development of a once-weekly (QW) oral non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV infected patients. Central to the success of this approach is the ability to produce an orally bioavailable NNRTI with a long plasma half-life that can enable QW dosing with forgiveness (human t1/2 ≥ 80 h). The drug design and optimization strategies to deliver on this relatively unprecedented objective will be presented and includes retrospective clinical PK analysis, prospective use of in silico clearance, unbound PK parameter utilization, and 2-compartment human PK projections using allometric scaling. Ultimately, this approach delivered a clinical candidate with human PK supportive of QW dosing that is envisioned to be a potential component of a future QW HIV treatment regimen.

Optimizing predicted human PK in action: Case study of the discovery of a once-weekly NNRTI for treating HIV-1 infection

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.