<p>This paper presents a mathematical model to investigate the co-infection with human immunodeficiency virus (HIV) and Zika virus (ZIKV) in Colombia and Brazil, where the first cases were reported in 2015. The model considers the sexual transmission dynamics of both viruses and vector-host interactions. We begin by exploring the qualitative behaviour of each model separately. We then analyze the dynamics of the co-infection model using the thresholds and results defined separately for each model. The model also considers the impact of intervention strategies, such as personal protection, antiretroviral therapy (ART), and sexual protection (condom use). Using available and assumed parameter values for Colombia and Brazil, the model is calibrated to investigate the long-term co-infection dynamics, the influence of specific parameters, and the potential effect of implementing these intervention strategies on co-infection spread. The study’s results revealed that the duration of Zika infection is a critical factor influencing the burden of co-infection cases. Additionally, bed nets and use of condoms are essential for disease control, while ART is less emphasized due to the cost-effectiveness of condom use.</p>