The prevalence of low-level viraemia and its association with virological failure in people living with HIV: a systematic review and meta-analysis

Low-level viraemia (LLV) following antiretroviral therapy (ART) in people living with HIV (PLWH) has not received sufficient attention. To the determine the prevalence of LLV and its association with virological failure (VF), we systematically reviewed evidence-based interventions for PLWH. We searched PubMed, the Cochrane Library, Embase, and Web of Science from inception to 22 May 2024. Cohorts with samples sizes smaller than 1000 in size were excluded. Data from 16 cohort studies, encompassing 13,49,306 PLWH, revealed a pooled prevalence of LLV of 13.81%. Relative risk (RR) and 95% confidence intervals (CI) identified the following risk factors for LLV: viral load (VL) ≥ 10⁵ copies/mL at baseline (1.79, 1.11–2.88), AIDS-defined illness at baseline (1.24, 1.10–1.40), and protease inhibitor-based regimen at ART initiation (1.53, 1.45–1.62) are the risk factors for LLV. Conversely, CD4 count ≥200 cells/μL at baseline (0.90, 0.82–0.98), non-nucleoside reverse transcriptase inhibitor-based regimen (0.81, 0.68–0.96) and the integrase strand transfer inhibitor (INSTI)-based regimen (0.60, 0.42–0.85) were associated with a reduced risk of LLV. Pooling the adjusted hazard ratio (aHR) and the 95% CI, we found that LLV increased the risk of VF with rising VL among 96,711 PLWH (aHR 2.77, 95% CI 2.03–3.76) and increased the risk of all-cause mortality at high VL levels among 14,229 PLWH (aHR 1.66, 95% CI 1.16–2.37). Therefore, the prevalence of LLV in PLWH should not be overlooked. This study aims to guide better management strategies to improve clinical outcomes in patients with LLV.