Advances in HIV prevention tools have outpaced our ability to ensure equitable access to these tools. Novel approaches to reducing known barriers to accessing HIV prevention, such as stigma and logistical-related factors, are urgently needed. To evaluate the efficacy of a randomized controlled trial with four intervention arms to address barriers to HIV/STI testing uptake (primary outcome) and PrEP use, depression, and HIV test results (secondary outcomes). We tested a 2 × 2 research design: main effect 1-stigma-focused vs. health information evaluation-focused counseling, main effect 2-offering HIV/STI testing appointments in person vs. at home with a counselor via video chat, and the interaction of the main effects. Participants (N = 474) residing in the southeastern USA were screened and enrolled in a longitudinal trial. Intervention efficacy was established using generalized linear modeling with binomial or Poisson distributions. Intervention efficacy demonstrated an increase in HIV/STI testing uptake when testing was made available at home with a counselor via video chat vs. in person (83% vs. 75% uptake, p < .05), and participants were also more likely to test positive for HIV over the course of the study in the at-home condition (14.5% vs. 9.4%, p < .05). Stigma-focused counseling resulted in lower depression scores and greater uptake of PrEP among participants < 30 years of age when compared with health information counseling (15.4% vs. 9.6%, p < .05). In order to prevent further disparities between HIV prevention advances and access to HIV prevention tools, we must prioritize improvements in linking people to care. Novel interventions, such as those proposed here, offer a practical, evidence-based path to addressing long-standing barriers to HIV prevention strategies. Trial registration: NCT03107910.