Levels of Soluble CD40 Ligand (CD154) in Serum Are Increased in Human Immunodeficiency Virus Type 1-Infected Patients and Correlate with CD4(+) T-Cell Counts

CD40 ligand (CD40L or CD154) is a costimulatory molecule expressed mainly on activated CD4(+) T cells. Concentrations of the soluble form of CD40L (sCD40L) in serum were determined for a cohort of 77 human immunodeficiency virus type 1 (HIV-1)-infected patients before and after initiation of highly active antiretroviral treatment (HAART) by a quantitative enzyme-linked immunosorbent assay. Circulating sCD40L levels were higher by twofold in untreated patients than in healthy controls (means ± standard deviations [SD]: 1.41 ± 1.48 versus 0.69 ± 0.59 ng/ml; P < 0.001). HIV-1-infected patients classified as CD4 T-cell category 1 had significantly higher sCD40L levels than patients classified as CD4 categories 2 and 3 (mean ± SD: 2.08 ± 1.46 ng/ml versus 1.57 ± 1.58 [category 2] and 0.94 ± 1.25 ng/ml [category 3]; P = 0.046), while no correlation with clinical categories A, B, and C was found. Individual serum sCD40L levels correlated with CD4(+) T-cell counts (P = 0.039) but not with viral load, gamma globulin levels, or acute-inflammatory-response markers. After 8 to 12 months of HAART, a further threefold increase of serum sCD40L levels, which paralleled the increase of CD4(+) T-cell counts, was observed. These novel findings suggest that sCD40L measurement in HIV-1-infected patients could serve as a new surrogate marker useful in the assessment of treatment efficacy, especially in settings where well-equipped laboratories and funding required for CD4(+) T-cell count and viral load measurements are not available

Differential sensitivity of thick and thin fibers to HIV and therapy-induced neuropathy

The study assessed HIV-related and anti-retroviral therapy-induced neuropathy in myelinated and unmyelinated nerve fibers. One hundred consecutive HIV patients were examined clinically and standard nerve conduction velocities were measured. In addition, electrically induced sympathetic skin response (SSR) was assessed in the palms and soles. The difference in delay of SSR in palms and soles (Delta SSR) was calculated as an indirect measure of C-fiber conduction velocity. Thick fiber conduction velocities significantly decreased with age and increasing stage of the disease, whereas no effect of stage was found for Delta SSR (p=0.6). In contrast, medication of at least one of the most known neurotoxic drugs zalcitabine, stavudine, or didanosine did not result in significantly lower conduction velocities in thick fibers (51.29 +/- 3.4 m/s vs. 50.86 +/- 3.5 m/s), but was related to an increased Delta SSR. Delta SSR allows an indirect measurement of C-fiber conduction velocity. In HIV this measure of unmyelinated sympathetic fibers was most sensitive to anti-viral treatment whereas conduction velocity of myelinated somatic fibers was more sensitive to disease-related neuropathy. The results suggest that HIV neuropathy preferably affects myelinated and anti-retroviral therapy unmyelinated fibers. (c) 2007 Elsevier B.V. All rights reserved

Polyneuropathy induced by HIV disease and antiretroviral therapy

Objective: To investigate the underlying mechanisms of polyneuropathy induced by HIV infection or antiretroviral drugs. Methods: We tested 100 HIV patients (59 with AIDS). Ninety-three patients received antiretroviral drugs. Forty-four were treated with neurotoxic compounds (ddI, ddC, d4T). Nerve conduction velocities and the sympathetic skin response (SSR) in palms and soles were measured in all patients. In skin biopsies (ankle and thigh), the intraepidermal nerve fiber density (IENFD) and the number of epidermal fibers without contact to the basal membrane (fragments) were quantified using PGP9.5 staining. Results: Severity of the disease (CD4 + count) correlated to conduction velocities of peroneal (p &lt; 0.01, Spearmans rank correlation), sural (p &lt; 0.01) and median nerves (p &lt; 0.05/p &lt; 0.001, sensory/motor). In contrast, the duration of neurotoxic treatment did not impair conduction velocities (p &gt; 0.3) but correlated to reduced IENFD in the ankle (r = -0.24, p &lt; 0.05). Despite their reduced IENFD, patients with long neurotoxic treatment had a high number of fragments irrespective of their CD4 + count. Conclusions: Neurotoxic treatment appears to primarily impair thin fiber conduction, whereas HIV neuropathy is linked to large fiber impairment and reduction of fragments of nerve fibers. Significance: These findings emphasize the differential pattern of polyneuropathy in HIV patients caused by the infection or induced by antiretroviral treatment. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved

Impaired distensibility of ascending aorta in patients with HIV infection

<p>Abstract</p> <p>Background</p> <p>Our aim was to investigate the aortic distensibility (AD) of the ascending aorta and carotid artery intima-media thickness (c-IMT) in HIV-infected patients compared to healthy controls.</p> <p>Methods</p> <p>One hundred and five HIV-infected patients (86 males [82%], mean age 41 ± 0.92 years), and 124 age and sex matched HIV-1 uninfected controls (104 males [84%], mean age 39.2 ± 1.03 years) were evaluated by high-resolution ultrasonography to determine AD and c-IMT. For all patients and controls clinical and laboratory factors associated with atherosclerosis were recorded.</p> <p>Results</p> <p>HIV- infected patients had reduced AD compared to controls: 2.2 ± 0.01 vs. 2.62 ± 0.01 10^-6 cm² dyn^-1, respectively (p < 0.001). No difference was found in c-IMT between the two groups. In multiadjusted analysis, HIV infection was independently associated with decreased distensibility (beta –0.45, p < 0.001). Analysis among HIV-infected patients showed that patients exposed to HAART had decreased AD compared to HAART-naïve patients [mean (SD): 2.18(0.02) vs. 2.28(0.03) 10^-6 cm² dyn^-1, p = 0.01]. In multiadjusted analysis, increasing age and exposure to HAART were independently associated with decreased AD.</p> <p>Conclusion</p> <p>HIV infection is independently associated with decreased distensibility of the ascending aorta, a marker of subclinical atherosclerosis. Increasing age and duration of exposure to HAART are factors further contributing to decreased AD.</p