Phase I/II trial of thymosin fraction 5 and thymosin alpha one in HTLV-III seropositive subjects.

Forty-two male homosexuals and/or hemophiliacs with depressed helper/suppressor T-cell ratios were treated with one of three different doses of thymosin fraction 5 (TF5, 30, 60, and 120 mg), or a single dose of thymosin Alpha One (TA1, 600 micrograms), by daily subcutaneous (SQ) administration for 10 weeks, followed twice weekly for 4 weeks. No major toxicity was noted for any of the preparations tested, although three subjects treated with TF5 had to discontinue therapy because of severe local skin reactions. Of the doses and preparations tested, only 60 mg TF5 was capable of significantly improving (p less than 0.02) mean T-cell lymphoproliferative responses to alloantigens (MLR) for six HTLV-III seropositive subjects who were abnormal prior to therapy. Peripheral blood lymphocytes from subjects treated with 60 mg TF5 also exhibited a transient restoration of mean mitogen-induced interleukin-2 (IL-2) production to normal. No effects were observed with any of the four treatment regimens on absolute helper T-cell numbers, NK activity, antibody titers to HTLV-III, or in the expression of a variety of surrogate markers for acquired immunodeficiency syndrome (AIDS). Four of the six seropositive subjects treated with 60 mg TF5 exhibited a return to depressed baseline MLR, after switching to twice weekly injections. With a median follow-up time of 20 months, six cases of AIDS developed. However, none of the five subjects whose MLR improved following treatment progressed to AIDS. We recommend daily subcutaneous (SQ) administration of 60 mg (40 mg/m2) TF5 for use in combined modality trials, along with drugs capable of suppressing replication of HTLV-III.