A Randomized Controlled Study for the Evaluation of the Activity of a Triple Combination of Zidovudine, Thymosin-α1 and Interferon-α in HIV-Infected Individuals with CD4 Counts between 200 and 500 cells/mm3

Abstract

Our objective was to determine the safety and the activity of thymosin-α1 (Tα1) plus interferon-α (IFN-α) and zidovudine in human immunodeficiency virus (HIV)-infected patients with CD4 counts between 200 and 500 cells/mm3. The study was multicentre, Phase II, randomized and open label. Patients were randomized to receive triple therapy, or zidovudine plus IFN-α, or zidovudine alone. Ninety-two patients were enrolled. After 12 months, in the triple combination group there was a median increase from baseline of 69 CD4 cells/mm3; a decrease of 52 cells/mm3 and of 65.5 cells/mm3 was seen in the zidovudine plus IFN-α and in the zidovudine monotherapy groups, respectively. In the triple combination arm the increase in mean CD4 counts was significantly greater than that observed in the other arms, particularly in patients with baseline CD4 counts less than 350 cells/mm3. The plasma HIV RNA load in triple therapy group showed a mean peak decrease from baseline of 16 000 copies/ml after 5 months (versus a decrease of 5000 copies/ml in the zidovudine monotherapy group) that was sustained at 12 months (versus a mean increase of 7000 copies/ml in the zidovudine monotherapy group at 12 months). The triple combination was superior to both the other arms in terms of virological and immunological response. Our study, although based on regimens of clearly sub-optimal antiretroviral potency, addressed the issue of combined therapy directed at two different targets: the HIV replicative cycle and the immune system. The use of immunomodulating agents deserves further investigation in the context of more potent antiretroviral combinations.