LACK OF EFFICACY OF LOW-DOSE ORAL INTERFERON-ALPHA IN SYMPTOMATIC HIV-1 INFECTION - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Background: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete in hibition of HIV replication at IFN-alpha concentrations greater than o r equal to 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural h uman (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections w ithout additional treatment. Moreover, loss of HIV antibody seropositi vity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but co ntroversy on the efficacy of this treatment persisted. Methods: We stu died 559 adult Ugandan patients with WHO stage 2-4 HIV infection and a Karnofsky performance score of more than 50, who had not received any drugs with antiretroviral activity in the previous 3 months. The pati ents were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-alpha/day or placebo. The duration of treatment was exten ded from 28 weeks to 60 weeks 9 months after enrolment had started. At that time 222 subjects had already received 28 weeks of treatment and been discontinued from the study. Results: Both study groups were com parable with respect to all baseline characteristics studied, except t hat the nHuIFN-alpha group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 x 10(6)/l) than the placebo group (median 85.3 x 10(6)/l) (p=0.033). Therefore, all analyses were adjusted for CD4+ lym phocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-a and placeb o had similar mortality, disease progression rates, decline of CD4+ ly mphocyte counts and Karnofsky performance scores, and prevalence of sy mptoms. No patient reverted to HIV-1 seronegative antibody status. Ser ious adverse events were not seen. Quality control of the study medica tion documented that the active drug indeed contained IFN-alpha activi ty. Conclusions: The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-alpha/day in a population of African patients with symptoma tic HIV infection.