Background:
Significant medical need exists for antiretroviral agents that can be administered less frequently. GS-1720 is an orally bioavailable integrase strand transfer inhibitor (INSTI) with potent antiviral activity and physiochemical properties well-suited for a long-acting formulation. We are investigating the antiviral activity, safety, and pharmacokinetics (PK) of GS-1720.
Methods:
An open-label, multi-cohort Phase 1b study is being conducted in participants with HIV who are treatment-naïve or viremic and off antiretroviral therapy for at least 12 weeks. Based on safety and PK data from a Phase 1a study in healthy volunteers, participants are being administered GS-1720 on Day 1 and 2 and followed for a total of 10 days. The primary endpoint is plasma HIV-1 RNA (log[sub]…[/sub]10 copies/mL) change from baseline to Day 11. Secondary endpoints include plasma HIV-1 RNA change at Day 8 in addition to PK parameters and safety assessments. Genotypic and phenotypic sensitivity testing to drugs from the INSTI class is also being conducted from samples collected during screening and Day 11 visits.
Results:
Preliminary PK from the Phase 1a study showed a median half-life of 9.4 days with a single GS-1720 dose of 450 mg. In the first Phase 1b cohort (n=7; 6 males, 1 female and mean age 35) dosed daily on Day 1 and Day 2 with 450 mg, GS-1720 demonstrated an HIV-1 RNA mean log…10 copies/mL reduction at Day 11 of 2.44 (95% confidence interval [CI] 2.04, 2.83) and at Day 8 of 2.04 (95% CI 1.72, 2.36). No participants experienced any serious adverse events (AEs), Grade 3 or higher treatment-emergent AEs, or AEs related to study drug. No treatment-emergent INSTI resistance was observed.
Conclusions:
GS-1720 demonstrated potent antiviral activity and PK supportive of once weekly oral dosing while being well-tolerated. The observed >2 log…10 copies/mL decline in HIV-1 RNA and half-life >1 week in this cohort demonstrates the potential of GS-1720 as part of an oral weekly INSTI-based regimen.