Fatores de risco associados ao desenvolvimento de baixa viremia persistente em pessoas vivendo com HIV em uso de terapia antirretroviral: uma revisão sistemática

Abstract

Background: Antiretroviral therapy (ART) has markedly improved the clinical outcomes of people living with HIV (PLHIV), enabling sustained viral suppression and reducing morbidity and mortality. However, a proportion of patients exhibit recurrent detection of low–level viral RNA, known as persistent low-level viremia (LLV). LLV has been associated with increased risk of virologic failure, emergence of resistance mutations, chronic immune activation, and worse long-term clinical outcomes, although its determinants and implications remain heterogeneous across studies. Objective: To identify and analyze the risk factors associated with the development of persistent low- level viremia in PLHIV receiving ART. Methods: A systematic review was conducted following PRISMA 2020 guidelines. Searches were performed in PubMed and the Virtual Health Library using MeSH and DeCS descriptors related to HIV, antiretroviral therapy, risk factors, and low-level viremia. Observational studies evaluating risk factors for LLV in adults living with HIV were included. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS). Results: A total of 211 records were identified; ten studies met eligibility criteria and were included in the qualitative synthesis. LLV prevalence ranged from 5% to 15% across cohorts. Major risk factors included high baseline viral load, low baseline CD4 count, use of boosted protease inhibitor–based regimens, suboptimal adherence, prior treatment interruptions, presence of drug resistance mutations, and immune activation markers such as elevated monocyte count. Conversely, integrase inhibitor–based regimens demonstrated a protective effect. LLV was consistently associated with a higher risk of virologic failure and, in some settings, increased mortality and non-infectious comorbidities. Conclusion: Persistent low-level viremia is not a benign phenomenon and represents a meaningful indicator of virologic instability. Its identification warrants thorough adherence assessment, evaluation of drug resistance, and careful review of ART regimens. Harmonizing LLV definitions and expanding research on its mechanisms are essential to improving clinical management and preventing virologic failure among PLHIV.