With increased uptake and different medication options/dosing strategies for PrEP, it’s important to gain further insight into cases of possible PrEP ‘failure’ as well as increased understanding of how PrEP can affect HIV testing results and subsequent best clinical practices. This study describes medical records review of individuals reporting recent PrEP exposure at HIV diagnosis, baseline testing, and clinical management at a high-volume comprehensive sexual health and HIV services program in the U.K. (review period: January 2016 to December 2020). Out of 1030 individuals (96% MSM) diagnosed with HIV, 52/1030 (5%) reported recent PrEP use. Over two-thirds were determined to have recently acquired HIV. 19% reported having switched between daily and event-based dosing at least once since last negative HIV result, although 69% were mostly taking daily PrEP at diagnosis. Possible reasons for PrEP ‘failure’ included suboptimal adherence, disruption of medication supply/access resulting in its discontinuation, and modification of PrEP use following relationship status changes (a reason for PrEP ‘failure’ could not be identified in 13% of individuals who reported excellent medication adherence). Individuals with recent PrEP exposure had significantly lower baseline HIV viral load. Genotype was successfully performed for 83%, and of these individuals 30% had M184V/I (K65R was not observed). 48/52 attended a follow-up medical appointment [within 2 weeks] for ART initiation: all started a tenofovir-based NRTI backbone, and the third agent most commonly selected by providers was boosted darunavir, followed by bictegravir and dolutegravir. For 39 patients with 24-week follow-up information, all had achieved viral suppression.