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Serum HIV–1 RNA Levels Compared to Soluble Markers of Immune Activation to Predict Disease Progression in HIV–1–Infected IndividualsZangerle R.a · Steinhuber S.b · Sarcletti M.a · Dierich M.b · Wachter H.c · Fuchs D.c · Möst J.b
aAIDS Unit, Department of Dermatology and Venereology, University of Innsbruck, bInstitute of Hygiene and Ludwig–Boltzmann Institute of AIDS Research, University of Innsbruck, and cInstitute of Medical Chemistry and Biochemistry, University of Innsbruck and Ludwig–Boltzmann Institute of AIDS Research, Innsbruck, Austria
We assessed the value of HIV–1 RNA level compared to soluble immune activation markers, namely neopterin, β2–microglobulin and soluble TNF receptor 75 (sTNFR–75), to predict the change in the number of CD4+ T cells over a 1–year period, the development of AIDS, and survival (median follow–up 54 months). The study population comprised a cohort of 47 individuals for the analysis of the change in CD4+ T cells and survival (20 died), and a subgroup of 31 individuals with a baseline CD4+ T cells above 200×106/l for the development of AIDS (11 developed AIDS). HIV–1 RNA was measured from stored sera by quantitative PCR. The CD4+ T cell count obtained at study entry strongly correlated with baseline serum HIV–1 RNA levels (r = –0.47), and to a lesser extent with neopterin (r = –0.41) and β2–microglobulin (r = –0.29). The percentage change in CD4+ T cells over a 1–year period correlated with HIV–1 RNA levels (r = –0.32, p = 0.03), however, stronger correlations were found for neopterin, β2–microglobulin and sTNFR–75 (r = –0.51, r = –0.41, r = –0.42; p<0.01). No progression to AIDS or death was observed in individuals with baseline HIV–1 RNA levels below 20,000 copies/ml (10 of 31 and 15 of 47 individuals, respectively). A Cox’s proportional hazard model to predict AIDS revealed that HIV–1 RNA, the change in CD4+ cells over a 1–year period and sTNFR–75 levels independently predict AIDS; the change in CD4+ cells, the absolute CD4+ T cell count and neopterin were jointly significant to predict death. All results were adjusted for nucleoside monotherapy. In conclusion, to improve the predictive power, quantitation of HIV–1 RNA as a 'natural history marker’ may be supplemented by measurement of sTNFR–75 for 'early’–stage disease progression and neopterin for 'late’–stage disease progression.