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 tum or necrosis factor (sTNFR) types I and II are associated with progress ion to AIDS. To assess the utility of sTNFRs as markers for the assess ment of antiretroviral treatment, sTNFRs were sequentially determined in 47 asymptomatic HIV-1-infected men, who participated in a double-bl ind, randomized, placebo-controlled study. Progression to AIDS or seve re AIDS-related complex occurred in six zidovudine (ZDV)- and six plac ebo-treated subjects. During ZDV treatment (n = 28) both types of sTNF Rs declined compared with baseline and placebo, whereas they increased during placebo treatment (n = 19). A sustained decline of sTNFRs occu rred only in subjects who experienced no disease progression. During t he first 3 months of ZDV treatment, the hazard ratio for disease progr ession when sTNFR type II rose above the baseline value plus 5% was si gnificantly increased (hazard ratio: similar to 25; 95% confidence int erval: similar to 1.5-400; p < 0.03). Simultaneously determined CD4(+) counts and serum neopterin levels showed a similar pattern in progres sors and nonprogressors. Thus, in contrast to CD4(+) counts and neopte rin levels, sTNFR concentrations, especially those of the type II STNF R, appear to be valuable surrogate markers for monitoring the efficacy of ZDV treatment in asymptomatic HIV-1 infection.