ACC017 Showed Safety, Tolerability When Used as Antiretroviral Therapy

The novel integrase strand transfer inhibitor (INSTI), ACC017, was found to be effective and safe in patients with HIV using the treatment as an antiretroviral therapy (ART), according to 2 abstracts presented during the 26th International Workshop on Clinical Pharmacology of HIV, Hepatitis, and Other Antiviral Drugs 2025, which took place in Amsterdam from September 3-4, 2025.

INSTIs are a first- and second-line form of ART for people living with HIV. The INSTI ACC017 has previously shown anti-HIV activity that could make it an alternative form of ART for patients with HIV in the form of short-term monotherapy. Abstracts presented during this conference aimed to evaluate how safe and effective ACC017 could be in this context.

The first study¹ was a 2-phase analysis where adults with HIV who had never taken ART were randomized 2:10 to receive either placebo or ACC017 of 5, 40, or 80 mg daily for 10 days. The second phase of the study included all participants taking their previously assigned dose of either 5, 40, or 80 mg of ACC017 and combining it with emtricitabine/tenofovir alafenamide fumarate of 200 mg/25 mg for 18 days. Levels of HIV-1 RNA were evaluated using plasma samples, with the primary outcome being a log₁₀ reduction in RNA from baseline to day 11. The proportion of participants who had a concentration of less than 50 copies/mL of plasma HIV-RNA after day 29 acted as the other primary outcome.

There were 36 participants who were included in this study, with all those receiving ACC017 seeing significant reductions in HIV-RNA by day 11 compared with baseline. The mean decrease in the groups ranged from 1.44 to 2.34 log₁₀ copies/mL and none of the participants experienced viral breakthrough.

A total of 86.11% of the participants had HIV-RNA of less than 50 copies/mL at day 29. There were no discontinuations of the drug due to adverse events, and the safety profile was similar to that of placebo.

The second study² built on these findings, with an aim to evaluate the safety and efficacy of ACC017 when used as a single-dose in otherwise healthy adults. The study was conducted between January 24, 2024, and May 20, 2024, in a single center in China. Participants were randomly assigned to receive either a single dose of ACC017 of 5, 20, 40, 80, or 120 mg or placebo in a 4:1 ratio. Blood sampling, electrocardiograms, lab testing, vital sign monitoring, and pharmacokinetic analysis were used to assess the safety, tolerability, and pharmacokinetics of ACC017.

There were 36 participants included in this study, all of whom were aged between 18 and 55 years. There were 7 mild adverse events reported in those receiving ACC017 compared with 4 mild adverse events reported in the placebo group, indicating no significant difference in incidence of adverse events. The maximum plasma concentration was 193.7, 926.0, 900.8, 1671.7, and 2055.5 ng/mL, respectively, across each dose of ACC017. The average areas under the plasma concentration-time curve were 3191.7, 15252.4, 16918.9, 29286.7, and 31759.4 h*ng/mL.

The study showed that the use of ACC017 was safe and had nonlinear pharmacokinetics. “These findings suggest that a once-daily oral dosing regimen of ACC017 at low doses may achieve therapeutic concentrations, supporting its potential as a promising [ART] for HIV-1 infection,” the authors concluded.

References

1. Han N, Yang D, Wu L, et al. Antiviral activity, safety and PK/PD of ACC017 in antiretroviral naïve HIV-infected adults: a randomized, double-blind, placebo/dose-parallel-controlled short-term monotherapy therapy. Br J Clin Pharmacol. 2025;91(suppl 1):16. doi:10.1002/bcp.70222

2. Hu C, Li Y, Zhou Y, et al. Single-dose pharmacokinetics and safety of ACC017, a novel HIV integrase inhibitor, in healthy adult participants: a first-in-human study. Br J Clin Pharmacol. 2025;91(suppl 1):24-25. doi:10.1002/bcp70237