Preexposure prophylaxis (PrEP) reduces new human immunodeficiency virus(HIV) infections by up to 96% and is recommended for key populations by the World Health Organization. Understanding the knowledge and willingness to use PrEP is essential for effective implementation. This study assessed these factors and identifiedcharacteristics associated with differences in knowledge among key populations in Kampala, Uganda. We administered a cross-sectional survey to a systematic sample of 497 participants from fisherfolk (283, 56.9%), men who have sex with men (MSM) (93, 18.7%), and female sex worker (FSW) (121, 24.4%) communities in Kampala Central, where PrEP had not yet been rolled out. Data on sociodemographic characteristics, PrEP awareness, and HIV-related behavioralfactors were collected. Knowledge about PrEP was measured using an adopted questionnaire comprising five key questions about PrEP knowledge, graded as no knowledge, some knowledge and good knowledge. Ordered probit regression models were used to analyze the associations of independent factors with PrEP knowledge levels. Participants had a mean age of 29±7.6 years. Ofthese, 257 (51.7%) reported having sex with women, 157 (31.6%) with men and 83 (16.7%) with both men and women. Self-reported HIV-positive status was 6.4% in fisherfolk, 11.8% in MSM and 27.3% in FSW. PrEP awareness stood at 62.4% overall, with the highest awareness in FSW (73.6%) and the lowest in fisherfolk (54.1%). Willingness to use PrEP was high across all groups (77.7%), although it was lower among FSW (66.9%). Multivariate probit analysis highlighted key independent factors associated with PrEP knowledge among fisherfolks and HIV-related concerns (Adj. Coeff = 0.54, 95% CI: 0.11, 0.97) and lack of PrEP awareness (Adj. Coeff = -0.99, 95% CI:-1.28, -0.70); among MSM, lack of PrEP awareness (Adj. Coeff = -1.74, 95% CI:-2.38, -1.10); and in FSW, tertiary education (Adj. Coeff = 1.53, 95% CI: 0.07, 2.99) and marital status (Adj. Coeff = 0.57, 95% CI=0.09, 1.05). MEshighlighted the influence of these independent factors at each knowledge level. Despite the high willingness to use PrEP, significant knowledge gaps exist, particularly concerning dosage and use duration, which are influenced by factors such as HIV concern and educational attainment. Tailored educational initiatives may bridge these gaps and enhance willingness to use PrEP.
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