KINETICS OF TUMOR-NECROSIS-FACTOR-ALPHA AND SOLUBLE TNFRII IN HIV-INFECTED PATIENTS TREATED WITH A TRIPLE COMBINATION OF STAVUDINE, DIDANOSINE, AND HYDROXYUREA

TNF-alpha is involved in the pathogenesis of HIV, and is known to enha nce HIV replication in vitro. In this report the kinetics of plasma TN F-alpha and sTNFRII in patients receiving aggressive antiretroviral th erapy and their relationship to HIV plasma RNA and CD4 cell counts wer e examined. Eleven patients participating in an open label study for a ssessment of safety, and of virological and immunological effects of s imultaneous treatment with d4T, ddI, and HU, were evaluated, The CD4 c ell count of the patients before treatment ranged from 65 to 374/mm(3) and their HIV plasma RNA ranged from 1.9 x 10(4) to 3.7 x 10(5) copie s/ml. The viral load in eight patients decreased significantly (mean, 1.9 log(10)). TNF-alpha and sTNFRII plasma levels pretreatment and at 8 weeks into therapy directly correlated with HIV plasma RNA, Pretreat ment circulating TNF-alpha levels of 25-114 pg/ml (mean, 56 pg/ml) dec reased by more than twofold in seven patients, The change in TNF-alpha levels inversely correlated with the change in absolute CD4 cell numb er. Detailed kinetics of TNF-alpha and sTNFRII measured at weeks O, 1, 2, 4, 6, 8, and 12 paralleled those of HIV plasma RNA, A rapid declin e in these soluble markers was always observed at week 1 together with the HIV plasma RNA response, Three patients maintained a high viral l oad as well as high TNF-alpha and sTNFRII. These data suggest that (1) combination therapy with d4T, ddI, and HU decreased viral load and ci rculating levels of TNF-alpha/sTNFRII; (2) an association exists betwe en the TNF-alpha/sTNFRII and HIV viral load; and (3) TNF-alpha/sTNFRII might be a useful surrogate marker for predicting efficacy of antiret roviral therapy.