Aymptomatic CMV viremia is associated with increased levels of serum amyloid A in patients with advanced HIV-infection.

Objective: We evaluated assays for the measurement of acute phase protein levels in plasma for their usefulness to identify sensitively an inflammatory response to active cytomegalovirus (CMV) infection in HIV-infected patients. Methods: Plasma samples were collected from 28 CMV-seropositive patients with advanced HIV-infection (CD4-cell count < 200/mu l) before commencement of antiretroviral therapy. Sensitivity, specificity, and area under receiver operating characteristic curve for the selected acute phase protein assays (haptoglobin, fibronectin, high-sensitivity C-reactive protein [hs-CRP], human interleukin-6, serum amyloid A [SAA], and human lipopolysacharide binding protein) were compared with results of a CMV specific PCR assay. Results: CMV viremia was detectable in 8/28 patients. Levels of SAA correlated well with those of hs-CRP (r' = 0.439, P = 0.019 [Spearman rank correlation]). Levels of SAA > 3 mg/L discriminated with 100% sensitivity and 40% specificity between HIV-infected patients with and without active CMV infection. Sensitivity of fibronectin was 100% and specificity 15% at a threshold-value corresponding with the lower limit of normal values as defined by the manufacturer of the assay (> 29 mg/dL). Levels of the other acute phase proteins evaluated did not correlate with detection of CMV-DNA in plasma. Conclusion: Increased levels of SAA indicate sensitively an inflammatory response to active CMV infection. Use of a CMV specific virological assay is required to confirm the specificity of a high SAA-level but may be limited to samples with high SAA-levels. Hence, screening for increased levels of SAA in patients with advanced HIV-infection may allow early identification of active CMV infection.