Transgender individuals face a disproportionately high global burden of HIV infection, often due to a combination of behavioral, social, and structural vulnerabilities. Combined prevention approaches integrating behavioral, biomedical, and social components have shown promise but remain under-evaluated in transgender contexts. This study aimed to analyze and compare the effectiveness of different HIV prevention strategies among transgender populations through a systematic review and network meta-analysis.

A systematic search following PRISMA-NMA 2020 guidelines was conducted in PubMed, SciELO, LILACS, and ScienceDirect (2000–2025) using descriptors related to HIV, combined prevention, and transgender populations. Only original quantitative studies reporting effect measures (mean, SD) were included. A network meta-analysis was performed comparing three intervention categories using condom use behavior as a common comparator: A) Restrictive sexual behavior + self-efficacy in safe sex; B) Restrictive sexual behavior + condom-protected sex; C) Restrictive sexual behavior + condom-protected sex + social support. Mean, SD, SE, and 95% confidence intervals were estimated, and interventions ranked using radial SUCRA.

Four studies and nine interventions met eligibility criteria. The most effective strategy was safer receptive sex among transgender individuals (SUCRA 84.3%), followed by safe sex with non-transgender men (SUCRA 66.11%). Direct and indirect comparisons indicated that interventions promoting safer receptive sexual practices among transgender individuals were more effective than those addressing general condom use only. The inclusion of gender-specific content and social support mechanisms appeared to enhance the impact of prevention strategies.