In MSM, long­acting injectable PrEP could outperform oral PrEP

Among men who have sex with men, the use of long-acting injectable pre-exposure prophylaxis, or PrEP, to prevent HIV infection has the potential to reduce HIV transmission more than oral PrEP, according to the results of a modelling simulation published in The Lancet HIV.

“PrEP use among [men who have sex with men (MSM)] in the United States has increased, but its uptake in this population has been slow. Additionally, an individual must take at least four doses per week to achieve intracellular drug concentrations consistent with 96% reduction in risk of HIV infection,” Brandon D.L. Marshall, PhD, associate professor of epidemiology in Brown University’s School of Public Health, and colleagues wrote.

“To address challenges associated with adherence to a daily pill-based regimen, injectable formulations of antiretroviral drugs are being tested as candidates for use as long-acting injectable PrEP. Recent studies have shown high interest in long-acting injectable PrEP among MSM.”

For their study, Marshall and colleagues simulated HIV transmission to a network of 11,245 MSM in Atlanta and estimated the efficacy of long-acting injectable PrEP using pharmacokinetic data from safety trials and raw data from macaque model studies. They evaluated the effect of long-acting injectable PrEP on the cumulative number of new HIV infections over the course of 10 years from 2015 to 2024. The effects were compared with two other scenarios: no PrEP availability and using daily oral PrEP exclusively at various coverage levels.

1,932 with long­lasting injectable PrEP. At 35% coverage, there were 1,582 new infections with daily oral PrEP and 1,330 with long­lasting injectable PrEP. Compared with no PrEP at 35% population­level coverage, long­acting injectable PrEP led to a 44% decrease in new HIV infections vs. 33% for daily oral PrEP.

In a model without either of the two PrEP methods, there were an estimated 2,374 new HIV infections between 2015 and 2024, yielding an average 10-year incidence of 3.57 per 100 person-years. Using either daily oral PrEP or long-acting injectable PrEP led to a decrease in the cumulative number of new HIV infections in the 10-year period, Marshall and colleagues reported. At 15% population-level coverage, for example, there were 2,048 new infections with daily oral PrEP and 1,932 with long-lasting injectable PrEP. At 35% coverage, there were 1,582 new infections with daily oral PrEP and 1,330 with long-lasting injectable PrEP. Compared with no PrEP at 35% population-level coverage, long-acting injectable PrEP led to a 44% decrease in new HIV infections vs. 33% for daily oral PrEP.

At any level of coverage, long-acting injectable PrEP outperformed daily oral PrEP in decreasing the cumulative number of new HIV infections between 2015 and 2024, according to the researchers. At 35% coverage, long-acting injectable PrEP prevented 1,044 infections, compared with daily oral PrEP, which prevented 792 — a 16% relative decrease in cumulative incidence, the researchers reported.

“The relative benefit of long-acting injectable PrEP was sensitive to the assumed efficacy of injections received every 8 weeks, discontinuation rates, and terminal drug half-life,” Marshall and colleagues wrote.

In a related editorial, Sarit A. Golub, PhD, MPH, professor in the department of psychology at Hunter College, and Chibuzo U. Enemchukwu, MD,instructor in clinical investigation and associate attending physician at The Rockefeller University, said modelling studies can provide insights into the hypothetical potential of a novel intervention like long-acting injectable PrEP, but are limited in their real-world application.

“At first glance, the superiority of long-acting injectable PrEP seems to be the result of its inherent properties. However, upon deeper inspection, the superior population-level efficacy of long-acting injectable PrEP will manifest only in the context of the real-world behavior of patients, providers, and systems,” they wrote. “Social and behavioral research is crucial to ensure that the necessary supports are in place to improve decision making, uptake, and most importantly, retention of new biomedical prevention products.” – by Jennifer Byrne

Disclosures: The researchers report no relevant disclosures. Enemchukwu reports funding from a KL2 grant from the National Center for Advancing Translational Sciences of the NIH, which is linked to The Rockefeller University’s clinical and translational science award. Golub reports being a principle investigator on an NIH-funded project for which Marshall is a co-investigator.