Is low-level HIV-1 viraemia associated with elevated levels of markers of immune activation, coagulation and cardiovascular disease?

Objectives: The clinical significance of low-level viraemia (LLV) during antiretroviral therapy (ART) is debated. We retrospectively investigated longitudinal levels of plasma markers associated with inflammation, altered coagulation and cardiovascular disease in Swedish HIV-positive adults in relation to LLV or permanent virological suppression during long-term ART. Methods: Plasma levels of C-reactive protein (CRP), D-dimer, vascular cell adhesion molecule 1 (VCAM-1), suppression of tumorigenicity 2 (ST2), growth differentiation factor 15 (GDF-15), soluble CD14 (sCD14), soluble CD163 (sCD163), interferon-γ-induced protein 10 (IP-10) and β-2-microglobulin were measured in 34 individuals with LLV (viral load 50–999 HIV-1 RNA copies/mL) and in matched controls with persistent virological suppression. Biomarker levels were analysed in samples obtained during episodes of LLV and follow-up samples obtained 1 year later (with similar timing for controls). All biomarkers were analysed using an independent sample t-test and analysis of covariance (ANCOVA) after logarithmic transformation. Log-rank analysis was applied for markers with concentration values out of range. Results: Compared with controls, patients with LLV had significantly higher levels of GDF-15 [geometric mean 3416 (95% confidence interval (CI) 804–14 516) pg/mL versus 2002 (95% CI 355–11 295) pg/mL in controls; P = 0.026] and D-dimer [mean 1114 (95% CI 125–9917) ng/mL versus 756 (95% CI 157–3626) ng/mL; P = 0.038] after adjustment for age, CD4 count nadir and type of ART. In the unadjusted t-test, only GDF-15 was significantly higher and in the log-rank test, both GDF-15 and D-dimer were significantly elevated. No significant differences were observed for the other biomarkers analysed. Conclusions: Although levels of inflammation markers were similar in ART recipients with and without LLV, persons with LLV had significantly higher levels of GDF-15 and D-dimer. These findings suggest a potential link between LLV and cardiovascular outcomes.