Oral PrEP Use by Transgender Men in Uganda: A Multi-method Evaluation.

HIV pre-exposure prophylaxis (PrEP) use is understudied among transgender men in sub-Saharan Africa. Seventy-five transgender men were enrolled in a prospective cohort through social media marketing and followed for 12 months (September 2021-January 2023). The primary outcome was PrEP adherence. Thirty in-depth interviews explored (1) knowledge of HIV and other sexually transmitted infections (STIs), (2) testing for HIV and STIs, (3) access to HIV/STI services, and (4) PrEP use and adherence counseling via point-of-care urine tenofovir assay. Data were analyzed using inductive content analysis. Median age was 27 years; 12-month retention was 81%. HBV, HIV, syphilis, chlamydia, and trichomonas prevalence was 4.1%, 2.7%, 2.7%, 2.7%, and 1.4%, respectively. Overall, PrEP uptake was 48%. Urine tenofovir test positivity and TFV-DP detection increased over time: 25%, 52%, 64%, 67%, and 39%, 52%, 50%, 63%, at the 3-, 6-, 9-, and 12-month visits, respectively. Four themes underscored the intricacies of transgender men's lived experiences: (1) Systematic rejection of gender non-conformity resulted in maladaptive coping behavior, increasing HIV acquisition risk; (2) Economic exclusion hindered social integration, but research participation created meaningful social connections; (3) While oral PrEP provided protection, maintaining adherence was difficult for those favoring post-exposure prophylaxis over PrEP itself; (4) Tenofovir urine testing initially raised concerns but later facilitated open conversations regarding adherence. Ultimately, competing priorities limited PrEP adherence. This first oral PrEP study with African trans men revealed low HIV/STI prevalence and moderate PrEP uptake/adherence. HIV programs should integrate HIV prevention delivery with sexual and mental healthcare for this population.ClinicalTrials.gov identifier NCT04867798.