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Soluble Tumor Necrosis Factor Receptors as Surrogate Markers for the Assessment of Zidovudine Treatment in Asymptomatic HIV-1 Infection

Godfried, Mieke H.; van der Poll, Tom; Mulder, Jan W.; Weverling, Gerrit J.; Endert, Erik; Lange, Joep M. A.; Sauerwein, Hans P.
JAIDS Journal of Acquired Immune Deficiency Syndromes: December 5th, 1995
CLINICAL SCIENCE: PDF Only

Summary:In untreated, asymptomatic human immunodeficiency virus type 1 (HIV-1) infection, elevated serum concentrations of soluble receptors for tumor necrosis factor (sTNFR) types I and II are associated with progression to AIDS. To assess the utility of sTNFRs as markers for the assessment of antiretroviral treatment, sTNFRs were sequentially determined in 47 asymptomatic HIV-1-infected men, who participated in a double-blind, randomized, placebo-controlled study. Progression to AIDS or severe AIDS-related complex occurred in six zidovudine (ZDV)- and six placebo-treated subjects. During ZDV treatment (n = 28) both types of sTNFRs declined compared with baseline and placebo, whereas they increased during placebo treatment (n = 19). A sustained decline of sTNFRs occurred only in subjects who experienced no disease progression. During the first 3 months of ZDV treatment, the hazard ratio for disease progression when sTNFR type II rose above the baseline value plus 5% was significantly increased (hazard ratio: ∼25; 95% confidence interval: ∼1.5-400; p < 0.03). Simultaneously determined CD4+ counts and serum neopterin levels showed a similar pattern in progressors and nonprogressors. Thus, in contrast to CD4+ counts and neopterin levels, sTNFR concentrations, especially those of the type II STNFR, appear to be valuable surrogate markers for monitoring the efficacy of ZDV treatment in asymptomatic HIV-1 infection.

*Department of Internal Medicine, †Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research; §National AIDS Therapy Evaluation Center; and Departments of ¶Clinical Epidemiology and Biostatistics, and #Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam; and ‡Department of Infectious Diseases, Municipal Health Service, Amsterdam, The Netherlands

Address correspondence and reprint requests to Dr. M. H. Godfried, Academic Medical Center, University of Amsterdam, Department of Internal Medicine F4-222, PO Box 22700, 1100 NE Amsterdam, the Netherlands.

Manuscript received December 2, 1994; accepted May 24, 1995.

© Lippincott-Raven Publishers.