Zero HIV acquisition, high persistence through 1 year with cabotegravir LA as PrEP for MSM, transgender men

“Zero HIV acquisition” is a milestone that long-acting (LA) cabotegravir as pre-exposure prophylaxis (PrEP) has realized in the PILLAR real-world trial, along with high persistence observed through 12 months among 201 men who have sex with men (MSM) and transgender men (TGM).

“There were zero cases of HIV acquisition found through the month 12 visit, supporting a robust and sustained effectiveness of cabotegravir LA in the real world,” said Dr Taimur Khan from Fenway Health, Boston, Massachusetts, US. “Persistence with cabotegravir LA was higher than previously reported with oral PrEP in some studies.”

At month 6, 85.1 percent of participants continued to receive cabotegravir LA injections, the definition of persistence in the trial, while 72.6 percent did so at month 12. [CROI 2025, abstract 196] This level of persistence compared favourably with findings from prior research on oral PrEP, including a national sample in the US in which the persistence on tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) through 12 months was 56.4 percent. [J Int AIDS Soc 2019;22:e25252]

As an alternative way to assess persistence, the proportions of injections administered within the visit window of every 2 months (Q2M) ± 7 days from the prior injection visit were consistently over 80 percent, with 85 percent of the 7^th dose administered by the target date at month 12.

Benefit of increased clinic visits

PILLAR was a phase IV implementation science trial designed to evaluate strategies for integrating cabotegravir LA for PrEP into the care of MSM and TGM in the US.

Throughout the 12-month trial, 71.6 percent of participants completed all 7 doses of cabotegravir LA Q2M injections.

While additional visits were required to adhere to the PrEP dosing, 94.2 percent of participants did not find attending Q2M clinical visits difficult. Additionally, 20.5 percent of participants interviewed towards the end of the trial perceived the increased clinic visits as beneficial for facilitating more frequent sexually transmitted infection (STI) checks.

“More frequent clinic visits with cabotegravir LA facilitate increased interactions with healthcare providers and early detection and treatment of STIs,” added Khan.

Build on robust clinical trials

The adaptation of cabotegravir LA as PrEP among MSM had been studied in the HPTN 083 trial, where cabotegravir LA was shown to be superior to daily oral TDF-FTC for preventing incident HIV infections in the intention-to-treat (ITT) population, as well as in the subgroup of 3,992 MSM (87.4 percent of ITT population). [N Engl J Med 2021;385:595-608]

HPTN 084, the sister trial of HPTN 083, enrolled TGM as a minority of participants. [Lancet 2022;399:1779-1789]

Of the 201 participants in PILLAR (median age 35 years), TGM constituted 6 percent, while the remainder were MSM. This exceeded the protocol-defined enrolment target of 2–4 percent for TGM participants.

Additionally, 22 percent of participants had not received oral PrEP in the 6 months prior to receiving cabotegravir LA, an observation “demonstrating cabotegravir LA’s potential for expanding PrEP adoption across varied populations,” as Khan suggested.

Few discontinuations of cabotegravir LA due to adverse events (AEs) were observed, with discontinuations due to injection site pain occurring in 3 percent of participants, similar to those due to an injection-related AE in HPTN 083 (2.4 percent).

“PILLAR reinforced the safety and effectiveness of cabotegravir LA across diverse populations and clinical settings, underscoring the importance of real-world PrEP studies to build on robust clinical trials,” concluded Khan.