Human immunodeficiency virus (HIV), which causes Acquired Immunodeficiency Syndrome (Aids), still affects millions of people worldwide. Despite recent advances in the understanding of biological mechanisms of viral replication, there are relevant gaps in the understanding of the virus-host relationship. Unraveling these gaps may lead to the development of new therapeutic strategies and the establishment of new biomarkers useful for the diagnosis and prognosis of the infection and its comorbidities. Research has been carried out with a focus on decoding gene regulation and silencing processes. Among these, microRNAs (miRNAs) stand out, small non-coding sequences responsible for mediating several cellular processes. They are found primarily in the cytoplasm but may be exported and found circulating and measured in blood samples. These studies have shown the role of miRNAs as biomarkers in different diseases, particularly in viral infections. They are expressed in T cells, cells that play an essential role in orchestrating an efficient antiviral response, and are the target of HIV infection. Therefore, in this study we discuss the main biological characteristics of miRNAs and the potential use of these nucleic acids in their free, circulating form, as indicators of risk or protection against HIV infection.Introduction: Human immunodeficiency virus (HIV), which causes Acquired Immunodeficiency Syndrome, still affects millions of people worldwide. Despite recent advances in the understanding of biological mechanisms of viral replication, there are relevant gaps regarding the virus-host relationship. Unraveling these complexities may lead to the development of new therapeutic strategies and the establishment of new biomarkers useful for the diagnosis and prognosis of infection and its comorbidities. Therefore, in this study we discuss the main biological characteristics of microRNAs and the potential use of these nucleic acids in their free circulating form as indicators of risk or protection against HIV infection. Methods: A narrative review of the literature was carried out in the following databases through keyword and/or health descriptor searches: i) Google Scholar; ii) CAPES periodicals portal; iii) United States National Library of Medicine (PubMed) and iv) Elsevier’s Science Direct library. The keywords “microRNA; HIV infection; circulating microRNA; biomarkers” were used to search the databases as mentioned above. Results: Circulating microRNAs (ci-miRNA) are closely related to numerous processes in the HIV infection pathophysiology. They are involved in viral latency, increased viremia, hepatic injury, heart dysfunction, pulmonary hypertension, immune response impairment, and participate in Kaposi’s sarcoma pathology. Additionally, these molecules may indicate protection in elite controllers, reduce viral replication and load, and be useful markers of the infection’s eclipse phase. Conclusion: Ci-miRNA levels are altered levels in individuals with HIV, playing a dual role in infection. Advances in research have shown that ci-miRNAs could differentiate stages of HIV infection and diseases associated with a viral infection and serve as biomarkers for antiretroviral therapy’s effectiveness through changes in their expression
