Soluble tumor necrosis factor receptors as surrogate markers for the assessment of zidovudine treatment in asymptomatic HIV-1 infection.
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: approximately 25; 95% confidence interval: approximately 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, University of Amsterdam, The Netherlands.
M H
MH
Godfried
T
T
van der Poll
J W
JW
Mulder
G J
GJ
Weverling
E
E
Endert
J M
JM
Lange
H P
HP
Sauerwein
D000386:AIDS-Related Complex / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004311:Double-Blind Method; D005500:Follow-Up Studies; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015497:HIV-1; D006801:Humans; D008297:Male; D019798:Neopterin; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis* / Q000737:chemistry; D012995:Solubility; D015215:Zidovudine / Q000627:therapeutic use*
D000998:Antiviral Agents; D015415:Biomarkers; D016655:HIV Core Protein p24; D018124:Receptors, Tumor Necrosis Factor; D001708:Biopterins; D015215:Zidovudine; D019798:Neopterin