OBJECTIVE: Disadvantaged populations, including inhabitants of developing countries as well as racial/ethnic and sexual minorities in the United States, are disproportionally burdened by human immunodeficiency virus (HIV) infection, delayed HIV diagnosis, and unfavorable HIV-treatment outcomes. HIV interventions targeting single behaviors (e.g., testing) in these populations have shown to be efficacious at producing behavioral and clinical change but have been unable to eliminate the social health disparities associated with syndemics (i.e., a set of connected risks, interacting synergistically, and contributing to excess burden of disease in a population). METHOD: This meta-analysis of 331 reports (clusters; number of effect sizes [] = 1,364) assessed whether multiple-behavior interventions that target clusters of syndemic risks are more efficacious for those in disadvantaged regions and social groups. RESULTS: Across the board, multiple-behavior interventions were more efficacious than single-behavior ones as well as passive control groups among samples from countries with lower log gross domestic product (GDP), lower Human Development Index (HDI), and lower Healthcare Access and Quality (HAQ) Index. CONCLUSIONS: Within the United States, the efficacy of multiple-behavior interventions was similar across different levels of representation of racial/ethnic and sexual minorities. The analyses used robust variance estimation with small-sample corrections to assess the differential effects of multiple-behavior interventions and Egger Sandwich test with the multilevel meta-analysis approach to detect selection biases. (PsycInfo Database Record (c) 2023 APA, all rights reserved).