Managing low-level HIV viraemia in antiretroviral therapy: a systematic review and meta-analysis

Objective HIV-1 management has advanced significantly with antiretroviral therapy (ART), yet challenges persist, including low-level HIV-1 viraemia (LLV). LLV presents a complex scenario, with varied definitions in the literature, reflecting uncertainties in its clinical interpretation. Questions arise regarding the underlying mechanisms of LLV, whether it signifies ongoing viral replication or stems from other factors. This study aimed to systematically review strategies for LLV management, providing insights into optimal clinical approaches. Methods MEDLINE, EMBASE, Cochrane Library, Web of Science and Canadian Agency for Drugs and Technologies in Health were searched for relevant literature on LLV management. We included studies published between 2004 and 2024, assessing interventions such as ART modification, genotypic resistance testing, adherence assessment, performing therapeutic drug monitoring, testing for chronic coinfections and assessing the viral reservoir via HIV DNA quantification. Meta-analyses were conducted where feasible. Results The systematic review identified 48 eligible records. Findings indicated limited evidence supporting the effectiveness of ART regimen modification in achieving virological suppression among individuals with LLV. However, studies assessing genotypic resistance testing revealed a significant association between resistance-associated mutations and virological suppression during LLV. Adherence to ART emerged as a critical determinant of treatment efficacy, with interventions showing promise in achieving viral suppression. The clinical utility of therapeutic drug monitoring in managing LLV remained inconclusive. Gaps in the literature were identified regarding follow-up scheduling, managing concurrent chronic infections and assessing inflammatory markers in LLV management. Conclusions While ART modification may not consistently achieve virological suppression, genotypic resistance testing may offer insights into treatment outcomes. Adherence to ART emerged as a crucial factor, necessitating tailored interventions. However, further research is needed to elucidate the clinical utility of therapeutic drug monitoring and other management strategies. The study highlights the importance of ongoing research to refine therapeutic approaches and improve patient outcomes in LLV management. PROSPERO registration number CRD42024511492. All data relevant to the study are included in the article or uploaded as supplementary information.