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Observational Study
. 2024 Aug;27(8):e26316.
doi: 10.1002/jia2.26316.

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

Allahna L Esber  1   2 , Suze Colt  1   2 , Ningbo Jian  1   2 , Nicole Dear  1   2 , Bonnie Slike  1   2 , Valentine Sing'oei  3   4 , Jonah Maswai  1   5 , Michael Iroezindu  1   6 , Emmanuel Bahemana  1   7 , Hannah Kibuuka  8 , Christina S Polyak  1   2 , Hendrik Streeck  9   10 , Neha Shah  1 , Trevor A Crowell  1   2 , Julie A Ake  1 ; AFRICOS Study Group
Affiliations
Observational Study

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

Allahna L Esber et al. J Int AIDS Soc. 2024 Aug.

Abstract

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.

Keywords: HIV; cohort studies; low‐level viraemia; multimorbidity; non‐communicable diseases; sub‐Saharan Africa.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Non‐infectious comorbidities at the enrolment visit by viral load category.
Figure 2
Figure 2
Biomarker concentration by viral load category at the enrolment visit. Dotted line = LLD; black line = median value; red outline = Bonferroni corrected p<0.004 positive association between viral load and biomarker concentration; blue outline = Bonferroni corrected p<0.004 negative association between viral load and biomarker concentration.
Figure 3
Figure 3
Interaction between low‐level viraemia and immune activation marker in the association with any non‐infectious comorbidity (NCD) at the enrolment visit. (A) Interaction between low‐level viraemia (LLV) and each immune activation marker in the association with any NCD. Each row is a separate model. (B−D) Predicted probability of any NCD by TNF‐α, CCL2/MCP‐1 and TNF‐RII levels comparing participants with undetectable or LLV at the enrolment visit.
Figure 4
Figure 4
Interaction between low‐level viraemia and immune activation marker in the association with elevated blood pressure, hyperglycaemia, hypercholesterolemia and renal insufficiency at the enrolment visit. Interaction between low‐level viraemia (LLV) and each immune activation marker in the association with select non‐infectious comorbidity. Each row is a separate model.
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