Initiation of Antiretroviral Therapy Reduces Number of Active HIV-Infected Cells

The administration of 3BNC117 with the initiation of antiretroviral therapy (ART) can help reduce the number of transcriptionally active HIV-infected cells and result in a faster decay of plasma HIV ribonucleic acid (RNA) and increased HIV CD8⁺T cell immunity compared with ART alone, the results of a study published in Nature Medicine showed.

The findings were consistent with other observations broadly neutralizing HIV antibody (bNAb) administration during ART interruption and could accelerate reservoir decay, investigators said.

Additionally, they found that the co-administration of 3BNC117 with or without romidepsin at ART initiation led to prolonged ART-free control during treatment interruption, specifically for individuals whose pre-ART viruses were sensitive to bNAb.

Study participants were randomized into 4 groups consisting of a 1:1:1:1 ratio, including ART alone, ART and romidepsin, ART and 3BNC117, or all 3 treatments.

Investigators screened individuals within 4 weeks before the baseline visit at day 0 and followed them until day 365 of ART or longer if they chose to enroll in the 12-week study. All individuals, aged 18 years or older, were newly diagnosed as ART-naïve with a confirmed HIV diagnosis and a CD4⁺T cell counts of more than 200 cells/mm3 at screening.

Recruitment took place between January 16, 2017, and March 3, 2020, with the last follow-up occurring July 17, 2021.

Individuals who had the lowest pre-ART plasma HIV RNA levels became suppressed within 7 to 17 days after initiation of ART, though it was not always sustained after 365 days of the therapy, according to investigators.

The daily decay rate in median HIV RNA was found to be faster for those on all 3 treatments, with a decrease of 16.9% at days 10 through 24. In the ART-only group and the ART and romidepsin group, the decline was 10% and 18.5%, respectively.

Additionally, between days 24 and 90, the decay rates were comparable among all groups.

In the 12-week study, 20 individuals chose to participate in monitored treatment interruption, but just 13 were included. This part of the study started at day 400 after ART initiation.

Four of the 5 individuals who had 3BNC117-sensitive pre-ART plasma viruses had ART-free virologic control.

Investigators reported that they identified no resistance variants against 3BNC117 during the study period.

The findings showed that adjunctive treatment with 3BNC117 at ART initiation led to higher rates of complete or partial ART-free virologic control during interruption for individuals who are 3BNC117-sensitive, according to investigators.

Furthermore, investigators found that the administration of 3BNC117 and/or romidepsin was generally safe and well tolerated, with a total of 114 adverse events (AEs) that were thought to be related to the study drugs.

A total of 29 AEs were related to 3BNC117, with fatigue and headache the most common. For romidepsin, there were a total of 85 AEs, with fatigue and nausea the most common.

Reference

Gunst JD, Pahus MH, Rosás-Umbert M, et al. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial. Nat Med. 2022. doi:10.1038/s41591-022-02023-7