Impact of low-level viremia on HIV non-viral load suppression in low and middle-income countries

Background: The World Health Organization (WHO) defined low-level viremia (LLV) as a viral load (VL) of 51–999 copies/mL, and LLV has been associated with an increased risk of virological failure and drug resistance. Limited information is available from low- and mid-income countries (LMICs), which predominantly use WHO guidelines in HIV program monitoring. We estimated pooled prevalence of LLV, non-viral load suppression (VLS), and association between LLV and non-VLS among people living with HIV in LMICs. Materials and methods: In this systematic review and meta-analysis, databases were searched for articles reporting the association between LLV and non-VLS in LMICs between January 2015 and December 2023. Participants with VL ≤50 copies/mL were considered fully suppressed and those with VL ≥1000 copies/mL were non-suppressed. Using random effects models, we computed the pooled prevalence of LLV, non-VLS, and their corresponding 95% confidence intervals (CIs). We compared pooled prevalence of LLV and non-VLS between children vs adults and between studies done in Africa vs Asia. Results: Sixteen studies with 1 159 317 people living with HIV were analyzed. Overall, pooled prevalence of LLV was 19.7% (95% CI: 15.8–23.6) and that of non-VLS was 8.6% (95% CI: 6.5–10.7). Prevalence of LLV was significantly higher among children compared to adults (25.8% vs 17.2%; P < 0.001) and higher among studies done in Africa compared to those in Asia (22.3% vs 15.6%; P < 0.001). Prevalence of non-VLS was higher among studies involving children compared to adults (17.7% vs 5.6%; P < 0.001), but lower among studies done in Africa compared to Asia 8.3% vs 9.0%; P < 0.001). Overall, LLV increased the risk of non-VLS on a subsequent VL test compared to fully suppressed (RR = 2.6; 95% CI: 2.2–3.1). Conclusions: LLV was associated with an increased risk of non-VLS. Stakeholders should consider reviewing guidelines for the threshold of VLS given that LLV was consistently associated with increased risk of non-VLS across all groups.