Impact of Post-exposure Prophylaxis on Pre-exposure Prophylaxis Initiation Among Men Who Have Sex with Men: A Nested Case-control Study.

While post-exposure prophylaxis (PEP) is considered a gate way to pre-exposure prophylaxis (PrEP), prospective evidence remains limited. This study aimed to investigate the association between PEP experience and subsequent PrEP initiation. A nested case-control study was conducted within a prospective cohort of men who have sex with men (MSM) in Qingdao, China. Cases were participants newly initiating PrEP, matched to four controls selected from participants who were at risk of initiating PrEP at the exact time the case occurred. The primary exposure was self-reported baseline PEP use, classified as never, ever, or recent use. Supplementary analyses examined PEP use at the visit immediately preceding PrEP initiation. A dichotomous exposure categorization grouping strategy was also applied across the above analysis (combining ever and recent users). Conditional Logistic regression estimated associations between PEP and PrEP initiation. Subgroup analyses were performed to assess the potential effect modification. A total of 59 cases and 234 matched controls were included. Baseline PEP experience was not significantly associated with subsequent PrEP initiation (ever use: aOR = 1.79, 95%CI: 0.86-3.69, P = 0.117; recent use: aOR = 1.52, 95%CI: 0.46-4.99, P = 0.488). This lack of a significant association persisted when ever and recent PEP users were combined into a single "prior use" category (aOR = 1.72, 95%CI: 0.88-3.35, P = 0.110). However, subgroup analyses showed that among participants who report recent recreational drug use, those with a history of PEP use were more likely to initiate PrEP (aOR = 2.25, 95%CI: 1.09-4.64, P = 0.029). These findings suggest that to effectively leverage PEP encounters as a gateway to sustained prevention, health systems should prioritize and intensify linkage interventions for high-risk groups identified during the PEP consultation, particularly individuals who use substances. Transforming PEP encounters into opportunities for tailored intervention can strengthen the HIV prevention cascade for those most in need.