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: similar to 25; 95% confidence interval: similar to 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.