Providing more high-risk men with access to a long-acting form of PrEP could help to reduce new cases of HIV in the United States.

The research, led by a team at the HPTN Modelling Centre, which is a collaboration between Imperial College London and the Fred Hutchinson Cancer Center in Seattle, finds that offering an injectable, long-acting form of the preventative medication – including switching existing users from daily tablets to the bimonthly (every 8 weeks) injectable form – could be effective in reducing new cases of HIV among men at high risk.

According to the authors, the approach could prevent around 10% more new infections than tablets alone at similar levels of usage, and that with increased coverage long-acting PrEP could contribute substantially towards reaching targets to end the HIV epidemic in the United States.

The findings, published in the journal The Lancet Regional Health Americas, are believed to be the first to include clinical trial data for injectable PrEP in epidemiological models for the US.

Dr Kate Mitchell, from the MRC Centre for Global Infectious Disease Analysis and lead author of the study, said: “Previous modelling studies have asked similar questions about real world effectiveness, but our study is the first dynamic modelling for the US to incorporate actual clinical trial data on long-acting PrEP. We show that if you can increase the coverage, and get more men on PrEP, we can have a much bigger impact on HIV rates and move closer to elimination goals.”

Preventing infections
Pre-exposure prophylaxis (PrEP) medication is a preventative measure which can be used by people who are HIV negative but at risk in order to reduce their risk of getting the virus.

It has been shown to be effective in preventing new cases of HIV among groups at high risk of infection – including men who have sex with men (MSM), and those with a partner who is HIV positive.

If you can increase the coverage, and get more men on PrEP, we can have a much bigger impact on HIV rates and move closer to elimination goals
Dr Kate Mitchell
Imperial College London
Previous clinical trials have shown that while PrEP tablets are effective, adherence (i.e. ensuring people take the medication consistently in order for it to be effective) is an issue. A new form of PrEP that only needs to be administered once every two months via injection can reduce these adherence issues.

Clinical trials conducted by the HIV Prevention Trials Network (HPTN) have shown the injectable form to be at least as effective as daily tablets, but the impact of injectable PrEP has not been directly measured at the population level.

In the latest study, researchers modelled the impact of the two forms of PrEP in a well-defined population of MSM in Atlanta, Georgia. They estimated new HIV infections among this population between 2022-2026, modelling scenarios where men either take daily oral PrEP (tenofovir disoproxil fumarate/emtricitabine) or the long-acting injectable form of PrEP (cabotegravir), compared to no PrEP at all.

PrEP medication spills from a container
Pre-exposure prophylaxis (PrEP) medication can be used by people who are HIV negative but at risk in order to reduce their risk of getting the virus. It has been shown to be effective in preventing new cases of HIV among groups at high risk of infection (Credit: Shutterstock / Alim Yakubov)
Based on current usage, they estimate that oral PrEP alone would avert more than one third of new HIV infections (36.3% (95% credible interval 25.6–48.7%)) compared to no PrEP. Switching people over from tablets to the injectable form of PrEP would likely prevent 44.6% new infections (95% CI 33.2–56.6%) compared to no PrEP.

Additionally, they found that increasing the coverage of PrEP by 20% beyond current usage, in addition to switching to the long-acting injectable form, could further decrease new cases of HIV, with the impact of the injectable form over daily tablets increasing to 30% over the 5-year period and taking Atlanta MSM around 60% towards reaching US targets to eliminate HIV (47%/54% fewer infections in 2025/2030).

Towards targets
However, the researchers highlight that there are limitations. The cost of the injectable form of PrEP is likely to be greater than daily tablets, which could be a barrier to use. In addition, the authors conclude that in order to achieve the US current HIV elimination goal of a 90% reduction in new HIV infections by 2030, 93% of all uninfected MSM would need to use long-acting PrEP, which they believe is unrealistic. The team explain that more also needs to be done to improve the diagnosis and successful treatment of HIV, to reduce transmissibility among people living with HIV.

Dr Mitchell adds: “We know PrEP can be effective in preventing new cases of HIV infections, and that both daily tablets and long-acting injection forms work well. Like contraception, we will ultimately need multiple methods of HIV prevention. Hopefully, making both daily and long-acting PrEP accessible will enable more people to get the interventions they need and reduce new cases of HIV.”

Professor Marie-Claude Boily, from the MRC Centre for Global Infectious Disease Analysis, said: “There is still a considerable HIV epidemic in the United States, and substantial prevention efforts will be needed to meet their ambitious HIV targets. These modelling studies are valuable to show the potential contribution that injectable PrEP could make and to demonstrate the efforts that still remains to be done to tackle HIV in the US. We are planning to expand this research to estimate the impact that injectable PrEP could have in other populations around the world and its potential contribution to reaching global HIV targets.”

The research was funded by the US National Institutes of Health (NIH) and the UK Research and Innovation (UKRI) Medical Research Council (MRC) and involved collaborators from multiple institutions in the United States, Puerto Rico and Brazil.