Three-Month Anti-HIV Vaginal Ring Shows Promise in Phase 1 Trial
核心洞察
A phase one trial of a three-month dapivirine vaginal ring showed promising results, with drug concentrations in women's blood at least as good as the current one-month ring.
The three-month ring contains 100mg of dapivirine, compared to 25mg in the one-month ring, potentially leading to increased adherence and reduced costs.
The study found that both rings were well-tolerated with similar adverse events, and no HIV (搜索) infections were reported during the trial.
A longer-acting vaginal ring that provides three months of HIV (搜索) protection may soon be available to women in South Africa. Early results from a phase one trial presented at the HIV Research for Prevention (HIVR4P) conference in Lima, Peru, indicate that the three-month dapivirine ring is safe and achieves drug levels comparable to the existing one-month ring. This development could significantly improve adherence, reduce costs, and offer a more convenient HIV prevention option.
The Population Council (搜索), the manufacturer of the current monthly dapivirine ring, is developing the three-month ring. The new ring contains 100mg of dapivirine, a higher dose than the 25mg in the monthly ring, designed to release the antiretroviral drug over an extended period.
Phase 1 Trial Results
The phase one trial, conducted at FARMOVS, a clinical research organization at the University of the Free State in Bloemfontein, enrolled 104 women. Participants used both the three-month ring and three consecutive one-month rings in two treatment phases. Researchers measured dapivirine levels in the blood and vaginal fluid at set intervals.
The study found that drug concentrations in the blood of women using the three-month ring were at least as good as, and in some cases better than, those achieved with the one-month ring. Specifically, dapivirine levels in the blood were either greater or equivalent throughout the 90-day period. The greatest difference was observed in the first month, with the three-month ring showing somewhat higher drug concentrations.
Professor Linda-Gail Bekker, CEO of the Desmond Tutu Health Foundation, noted that the three-month ring performed better than the one-month ring during the study, with improved drug levels.
Dapivirine levels in vaginal fluid were slightly higher in the first month with the three-month ring, and similar to the one-month ring in the subsequent two months. Overall, the data suggest that the three-month ring delivers more drug over time compared to using three consecutive one-month rings.
Safety and Tolerability
According to Jeremy Nuttall, senior director of preclinical sciences at the Population Council (搜索)’s Centre for Biomedical Research, both rings were well-tolerated, with no notable differences in safety findings and no HIV (搜索) infections reported. Adverse events were similar between the two rings, with the most common being vaginal discharge, vaginal candidiasis (搜索), and bacterial vaginosis (搜索). No serious adverse events occurred.
Implications for HIV Prevention
A longer-acting ring offers several potential advantages, including fewer insertions, fewer clinic visits, increased adherence, and reduced annual costs. Nuttall estimates that manufacturing the three-month ring could lead to a 60% reduction in annual costs compared to the one-month ring, with 67% fewer rings needing to be produced each year.
Bekker emphasized that the efficacy of the three-month ring, like the one-month ring, depends on consistent use. "It will only do its work if it is in place at the time of HIV (搜索) exposure," she said.
Regulatory Pathway and Future Availability
The Population Council (搜索) plans to submit the trial data to regulators, including the European Medicines Agency (EMA), to support approval of the three-month ring as a line extension of the existing one-month ring. This approach is possible because the study was designed in consultation with the EMA to ensure that the data would bridge the existing safety and efficacy data for the one-month ring.
Dr. Bríd Devlin, the Population Council (搜索)’s chief scientific officer, anticipates filing for regulatory approval with the EMA in early next year, with the hope of bringing the ring to market by the end of 2026. The target price for the three-month ring is $16, excluding distribution costs, which is expected to be more cost-effective on a monthly basis compared to the one-month ring at $12.8.
The Population Council (搜索) has a Memorandum of Understanding with South African pharmaceutical company Kiara Health (搜索) to potentially manufacture and distribute the three-month ring, shifting leadership of the dapivirine vaginal ring to sub-Saharan Africa.
Broader Context of Long-Acting PrEP
The development of the three-month ring is part of a broader effort to expand long-acting PrEP options for women in South Africa. Other options include long-acting cabotegravir (CAB-LA) injections, which provide two months of protection per shot, and a six-month injectable PrEP expected to be registered soon. These long-acting options are particularly important in a country where women face high rates of gender-based violence and may have limited autonomy over their sexual and reproductive health.