Persistent low-level viraemia is associated with non-infectious comorbidities in an observational cohort in four African countries

Introduction: People living with HIV (PLWH) have higher rates of non-infectious comorbid diseases (NCDs) than individuals without HIV. We characterized the risk of NCDs among PLWH with undetectable viral load and persistent low-level viraemia (pLLV) in the African Cohort Study (AFRICOS). We secondarily quantified the role of immune activation in the association between LLV and NCDs. Methods: AFRICOS enrols participants in 12 clinics in Uganda, Kenya, Tanzania and Nigeria. Participants on antiretroviral therapy ≥ 6 months without an NCD at enrolment were included. PLLV was defined as at least two consecutive visits with a detectable viral load <1000 copies/ml. We examined elevated blood pressure, hypercholesterolemia, hyperglycaemia, renal insufficiency and a composite variable of any NCD. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard modelling. Among a subset of participants with biomarker data, we assessed the interaction between viral load and 13 biomarkers in the association with any NCD. Results: From 23 January 2013 to 1 December 2022, 1755 participants met the inclusion criteria for these analyses. At the first eligible visit, the majority of participants had an undetectable viral load (n = 1375, 78.35%). Participants with pLLV had an increased rate of developing any NCD (aHR: 1.22, 95% CI: 1.02−1.47) compared to participants with an undetectable viral load. There was a statistically significant interaction between LLV and TNF-α, CCL2/MCP-1 and TNF-RII in the association with any NCD. Conclusions: PLLV was significantly associated with NCDs and immune inflammation in this population. Aggressive management of LLV may positively impact NCDs in PLWH.