Mecanismos moleculares associados ao envelhecimento precoce em pessoas que vivem com HIV: uma revisão sistemática

Abstract

Greater availability and expanded access to antiretroviral therapy (ART) have contributed to increased life expectancy among individuals living with HIV. Despite the advances achieved through early diagnosis, access to ART, and improved healthcare services, there remains a challenge in understanding the mechanisms that contribute to accelerated aging in people living with HIV when compared to HIV-negative individuals. The aim of this study is to systematically evaluate the existing literature on this topic, with the goal of identifying, synthesizing, and analyzing the main molecular mechanisms involved, while also providing a broader understanding of the clinical and biological implications of premature aging in the HIV-positive population. This systematic review followed the PRISMA 2020 guidelines. Studies were retrieved from the following databases: SciELO, PubMed, LILACS, Science Direct, and Web of Science, covering the period from 2014 to 2024. Data were extracted from the CAPES Journal Portal and analyzed using the CiteSpace software. Journal partitions and impact factors used in this study were obtained from the 2020 Journal Citation Report. A total of nine original studies were included, all published in English, which investigated different molecular biomarkers in adult populations with HIV, with or without ART, totaling 1,574 participants. The studies were assessed for risk of bias (using Joanna Briggs Institute criteria) and for certainty of evidence (GRADE system). Most studies showed a low risk of bias (66.7%), and four demonstrated moderate quality of evidence. Biomarkers were classified into three categories: primary (such as telomere shortening and epigenetic age), antagonistic (mitochondrial dysfunction and immunosenescence), and integrative (inflammatory microRNAs, cytokines, and intestinal dysbiosis). The analysis indicated that premature aging in people living with HIV results from a combination of epigenetic, immunological, and metabolic mechanisms that persist even under long-term ART. Additionally, the scientometric analysis identified three predominant thematic clusters in the literature: neurological effects and chronic immune activation; biological aging and social inequalities; and cardiovascular comorbidities associated with HIV. The molecular biomarkers analyzed in this review consistently indicate that people living with HIV exhibit signs of accelerated biological aging, even under viral suppression. These findings underscore the need to incorporate such biomarkers into clinical practice for individualized monitoring and comorbidity prevention, while also considering social determinants as important modulators of this process.