Kinetics of tumor necrosis factor α and soluble TNFRII in HIV-infected patients treated with a triple combination of stavudine, didanosine, and hydroxyurea

M. Nokta, R. Rossero, K. Loesch, Richard B Pollard

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

TNF-α is involved in the pathogenesis of HIV, and is known to enhance HIV replication in vitro. In this report the kinetics of plasma TNF-α and sTNFRII in patients receiving aggressive antiretroviral therapy and their relationship to HIV plasma RNA and CD4 cell counts were examined. Eleven patients participating in an open label study for assessment of safety, and of virological and immunological effects of simultaneous treatment with d4T, ddI, and HU, were evaluated. The CD4 cell count of the patients before treatment ranged from 65 to 374/mm3 and their HIV plasma RNA ranged from 1.9 x 104 to 3.7 X 105 copies/ml. The viral load in eight patients decreased significantly (mean, 1.9 log10). TNF-α and sTNFRII plasma levels pretreatment and at 8 weeks into therapy directly correlated with HIV plasma RNA. Pretreatment circulating TNF-α levels of 25-114 pg/ml (mean, 56 pg/ml) decreased by more than twofold in seven patients. The change in TNF-α levels inversely correlated with the change in absolute CD4 cell number. Detailed kinetics of TNF-α and sTNFRII measured at weeks 0, 1, 2, 4, 6, 8, and 12 paralleled those of HIV plasma RNA. A rapid decline in these soluble markers was always observed at week 1 together with the HIV plasma RNA response. Three patients maintained a high viral load as well as high TNF-α and STNFRII. These data suggest that (1) combination therapy with d4T, ddI, and HU decreased viral load and circulating levels of TNF-α/sTNFRII; (2) an association exists between the TNF-α/sTNFRII and HIV vital load; and (3) TNF-α/sTNFRII might be a useful surrogate marker for predicting efficacy of antiretroviral therapy.

Original languageEnglish (US)
Pages (from-to)1633-1638
Number of pages6
JournalAIDS Research and Human Retroviruses
Volume13
Issue number18
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology

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