Lack of e Y cacy of low dose oral interferon alfa in symptomatic HIV-1 infection : a randomised , double blind , placebo controlled trial
Background: Interferon alfa (IFN-á) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-á concentrations > 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-á resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but controversy on the eYcacy of this treatment persisted. Methods: We studied 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 patients were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-á/day or placebo. The duration of treatment was extended from 28 weeks to 60 weeks 9 months after enrolment had started. At that time 112 subjects had already received 28 weeks of treatment and been discontinued from the study. Results: Both study groups were comparable with respect to all baseline characteristics studied, except that the nHuIFN-á group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 × 10/l) than the placebo group (median 85.3 × 10/l) (p=0.033). Therefore, all analyses were adjusted for CD4+ lymphocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-á and placebo had similar mortality, disease progression rates, decline of CD4+ lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms. No patient reverted to HIV-l seronegative antibody status. Serious adverse events were not seen. Quality control of the study medication documented that the active drug indeed contained IFN-á activity. Conclusions: The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-á/day in a population of African patients with symptomatic HIV infection. (Sex Transm Inf 1998;74:265–270)