Predictive value for survival of soluble tumor necrosis factor receptors p55 and p75 during zidovudine-containing treatment in symptomatic human immunodeficiency virus type 1 infection.
Previous studies of asymptomatic human immunodeficiency virus (HIV) infection have shown that serum levels of soluble tumor necrosis factor receptors (sTNFR) are good predictors of disease progression and clinical outcome during zidovudine (ZDV) therapy. The present study of symptomatic HIV infection was designed to evaluate whether sTNFR p55 and p75 at weeks 0 (pretreatment) and 24 and 48 are predictors of death < or = 3 years after the start of ZDV 1,000 mg alone or combined with low-dose interferon-alpha (ZDV 500 mg + IFN-alpha 3 MIU three times weekly). CD4+ T-cell numbers and serum neopterin were analyzed in a similar way. Forty previously untreated symptomatic HIV-infected persons with CD4+ T-cell numbers > or = 150 x 10(6)/L were included. At baseline, in the nonsurvivor group, mean age (42.1 vs. 34.4 years, p = 0.002) and neopterin (24.7 vs. 18.0 nmol/L, p = 0.02) were higher, whereas mean CD4+ T-cell counts (202 vs. 295 x 10(6)/L, p = 0.02) were lower than in the survivors. All analyses were adjusted for age. For the pretreatment marker values, a significant relative risk (RR) for death was noted only in the univariate analysis for sTNFR-p55 > 1.7 ng/ml [RR 3.1; 95% confidence interval (CI) 1.1-8.8; p = 0.04]. During therapy, CD4+ counts < 200 x 10(6)/L at week 24 and 48 and neopterin > 20 nmol/ml at week 48 were independent predictors of survival in the uni- and multivariate analysis. Marker values relative to baseline were not predictive. sTNFR-p55 and p75 were of little use as surrogate markers for clinical efficacy during ZDV-containing drug regimens in symptomatic HIV-infected patients with CD4+ counts 150 x 10(6)/L.
Frissen
P H
PH
Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
Weverling
G J
GJ
Endert
E
E
Jansen
J
J
Sauerwein
H P
HP
Lange
J M
JM
D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D015497:HIV-1; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D011237:Predictive Value of Tests; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012306:Risk; D015215:Zidovudine / Q000627:therapeutic use*
D015703:Antigens, CD; D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D001708:Biopterins; D015215:Zidovudine; D019798:Neopterin