Prevalence and factors associated with pre-exposure prophylaxis adherence among HIV-negative partners in serodifferent relationships attending selected health facilities in Gulu District, Uganda

Background Globally, an estimated 41.0 million people were living with HIV in 2025, with sub-Saharan Africa continuing to bear a substantial proportion of the global HIV burden. In Uganda, approximately 1.5 million people are living with HIV. Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is an established HIV pre-exposure prophylaxis (PrEP) option for individuals at substantial risk of HIV acquisition. However, the HIV prevention landscape has expanded to include additional PrEP options, including the dapivirine vaginal ring and long-acting injectable cabotegravir (CAB-LA), while twice-yearly injectable lenacapavir was recommended by WHO as an additional PrEP option in 2025. Despite these advances, oral TDF/FTC remains an important PrEP option, and understanding adherence to oral PrEP remains relevant for optimizing its effectiveness and informing adherence-support strategies in settings where it is used. Therefore, this study aimed to determine the prevalence of and factors associated with PrEP adherence among HIV-negative partners in serodifferent relationships attending four selected health facilities in Gulu District, Uganda. Methods A cross-sectional study was conducted in four selected health facilities in Gulu District, Uganda, namely Gulu Regional Referral Hospital (GRRH), TASO Gulu Clinic, Awach Health Centre IV, and Layibi Techo Health Centre III from 1st July to 31st August 2024. A total of 460 HIV-negative partners in serodifferent relationships were consecutively recruited, with proportional allocation across facilities. Data were collected using a modified AIDS Clinical Trials Group (ACTG) adherence questionnaire. Descriptive statistics were used to estimate the prevalence of good adherence. Because the prevalence of PrEP adherence was high (92.2%), modified Poisson regression with robust standard errors was used to identify factors associated with PrEP adherence. Adjusted prevalence ratios (aPRs) with 95% confidence intervals (CIs) were reported. Results The prevalence of good PrEP adherence was 92.2% ( n = 424; 95% CI: 89.4–94.3). High perceived risk of HIV acquisition (aPR = 1.54; 95% CI: 1.23–1.95; p < 0.001), tertiary level of education (aPR = 1.04; 95% CI: 1.00–1.05; p = 0.03), and absence of fear of side effects (aPR = 1.19; 95% CI: 1.02–1.39; p = 0.025) were significantly associated with good adherence. Conversely, absence of family support (aPR = 0.91; 95% CI: 0.85–0.97; p = 0.012) and forgetfulness (aPR = 0.95; 95% CI: 0.92–0.99; p = 0.018) were significantly associated with poor adherence. Conclusion This study found a high prevalence of self-reported PrEP adherence among HIV-negative partners in serodifferent relationships in Gulu District. Adherence was influenced by tertiary education, perceived HIV risk, side-effect concerns, forgetfulness, and family support. These findings highlight the need for multi-level interventions, including enhanced counseling to sustain risk perception, strategies to manage side effects, adherence support tools such as reminders, and greater family involvement. Strengthening adherence monitoring systems and preparing for the integration of long-acting PrEP options will be critical for sustaining HIV prevention efforts in Uganda.