MicroRNAs are considered as potential biomarkers, agents, or therapeutic targets; few studies have addressed the expression of miRNAs in treatment-naïve patients infected with HIV-1. The aim of this study was to assess plasma relative circulating miRNA expression profiles in treatment-naïve Mexican patients with HIV/AIDS and healthy individuals using a commercial array. A low CD4+ T cell count and high viral load were found in all patients. Decreased relative miRNA-296-5p expression was observed in patients; moreover, this was the only miRNA that showed differences between the two groups. Thus, we measured the absolute expression of miR-296-5p by qPCR, confirming the result with statistically significant differences (P < 0.05). There is evidence that miR-296-5p regulates the expression of the PIN1 gene, which encodes the peptidylprolyl Cis/Trans isomerase NIMA-Interacting-1, that is involved in different stages of the biological cycle of HIV-1, this relationship is corroborated by bioinformatics analysis and ELISA assay was used to measure plasma levels of PIN1. The decreased expression of miR-296-5p found in naïve patients with HIV infection suggests a regulatory activity of this miRNA on virus replication, making it a potential therapeutic agent against HIV. Finally, miR-296-5p could be inhibiting the virus transcription by regulating genes different than PIN1.