Background: HIV prevention trials enroll participants with high vulnerability to HIV and provide access to an enhanced HIV prevention package, including PrEP. HVTN 704/HPTN 085 was a randomized clinical trial evaluating VRC01 for HIV prevention in MSM and TGW in the Americas and Switzerland. We conducted a post-hoc analysis to characterize bSTI burden and evaluate the association of PrEP use with bSTI incidence among trial participants. Methods: We included trial participants who received at least one VRC01/placebo infusion and had bSTI results from at least one bSTI visit (baseline and every 6 months). Participants received education about oral PrEP and could opt to use it. Prevalence of bSTI was summarized at each visit and categorized by socio-demographics, geographic region, and PrEP use (a time-varying covariate indicating self-reported PrEP use). We estimated incidence rates (for 100 person-years at risk [PYR]) of first bSTI occurrence among those who were negative at baseline, categorized by PrEP use. Cox proportional hazards models were used to evaluate the effect of PrEP use on bSTI incidence, additionally adjusted for age, region, race, ethnicity, and VRC01/placebo. Results: The analysis included 2687 participants, of whom 31.8% initiated PrEP during follow-up. The table summarizes bSTI baseline prevalence by region and incidence rates by PrEP use. The baseline prevalence of any bSTI was highest among <20yo (35.7%), Hispanic/Latinx (32.4%), non-Black/non-Whites (32.1%), TGW (35.3%), and MSM (28.9%). Oropharyngeal (gonorrhea 6.5%) and rectal bSTI were more prevalent (chlamydia 9.0% and gonorrhea 5.8%) than genitourinary bSTI (chlamydia 3.0% and gonorrhea 0.9%) at baseline. PrEP use was significantly associated with increased hazard of any bSTI (HR 1.7, 95%CI 1.4-2.1), chlamydia (HR 1.7, 95%CI 1.3-2.2), gonorrhea (HR 1.8, 95%CI 1.4-2.5), and syphilis (HR 1.9, 95%CI 1.3-2.8). Conclusions: HVTN 704/HPTN 085 engaged communities with significant HIV/STI vulnerability. While on PrEP, users had higher rates of bSTI, suggesting risk compensation and underscoring the need for advancing bSTI testing and prevention measures in HIV prevention trials.