Plasma levels of soluble CD30, tumour necrosis factor (TNF)-alpha and TNF receptors during primary HIV-1 infection: correlation with HIV-1 RNA and the clinical outcome.

Abstract

The immunological and virological events associated with primary HIV-1 infection have a major impact on the course of HIV-1 disease, and the identification of early predictors during primary HIV infection is critical for the therapeutic strategy. Eighteen consecutive patients with primary HIV infection were followed for a median of 398 days. Clinical status, CD4+ T-cell counts, and plasma samples were obtained weekly from enrollment until week 6, then at weeks 12, 24 and 52, and every 6 months thereafter. Seroconversion was assessed by anti-HIV-1/2 antibodies and Western blot analysis. HIV-1 RNA in plasma was quantified by Amplicor HIV Monitor test. Samples were assayed for immune complex-dissociated p24 antigen, tumour necrosis factor (TNF)-alpha, soluble TNF receptor (sTNFR)-1, sTNFR-II, sCD30 and sCD8 by enzyme immunoassays. Outcome was defined as entering clinical category B or C according to the Centers for Disease Control and Prevention criteria. As a control group, we included 23 HIV-1-negative healthy blood donors. Plasma levels of sCD30, TNF-alpha and sTNFR were significantly higher in HIV-1-infected patients than in controls, and were positively correlated with each other and with values of HIV-1 RNA. Patients who developed an outcome (n = 4) had significantly higher levels of sCD30, TNF-alpha and sTNFR compared with those who did not. Multivariate logistic regression analysis showed that sCD30 and TNF-alpha were the best predictors of outcome independently of CD4+ T-cell counts. During primary HIV infection, a persistent immune activation may be associated with a poor clinical outcome. The identification of sCD30 and TNF-alpha levels in plasma as early predictors of outcome in primary HIV infection, may direct the implementation of early therapeutic strategies in patients with elevated risk of disease progression.