Higher plasma D-dimer is associated with increased risk of distal sensory polyneuropathy in people with HIV

Although plasma D-dimer levels are high in patients with some types of peripheral neuropathy, this has not been examined in people with HIV (PWH). We tested the hypothesis that higher plasma D-dimer levels would be related to the presence and severity of HIV-associated distal sensory peripheral neuropathy (DSP). Participants in a U.S. research cohort were evaluated using standardized clinical examinations and interviews for findings of DSP and distal neuropathic pain by trained clinicians. D-dimer levels in the two neuropathy groups (0 or 1 versus 2 or more neuropathy signs), were compared using the Wilcoxon rank sum test. Multivariable regression assessed the effects of age and other covariates. Participants were 185 PWH, mean (SD) age 56.2 (8.10), 19.7% females, 56.4% non-White, median nadir and current CD4 lymphocytes 107 (IQR 20, 210) and 567 (348, 817), undetectable plasma HIV RNA 79.9%; and 210 people without HIV (PWoH), mean age 50.6 (15.8) years, 38.6% female, 18.1% non-White. Among PWH, 50 had 0 signs, 47 had 1 and 88 had 2 or more; among PWoH, 149 had 0 signs, 38 had 1 sign, and 23 had 2 or more signs (PWH versus PWoH p = 1.36e-20). Log10 plasma D-dimer levels were higher in PWH than PWoH (2.78±0.233 versus 2.66±0.253, p = 5.20e-6). D-dimer was significantly higher in those with DSP (2 or more DSP signs) compared to those without (p = 0.0017, Wilcoxon rank sum test). In multivariable analyses this relationship was independent of potential confounders. This association persisted in a sensitivity analysis that was limited to only the subset of participants with undetectable plasma HIV RNA (Wilcoxon p = 0.041). In PWoH, d-dimer levels were numerically higher in those with DSP (2.75±0.206 versus 2.65±0.256, p = 0.0604). Neuropathy symptoms (pain, paresthesias) were not significantly related to D-dimer levels. Since DSP is a major cause of disability in PWH, identifying biomarkers such as D-dimer may enable future investigations to assess prognosis or response to therapy.