Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection: a randomised, double blind, placebo controlled trial.

Abstract

Background:Interferon alfa (IFN-) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-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-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-/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-group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 × 10 6 /l) than the placebo group (median 85.3 × 10 6 /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-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-activity. Conclusions:The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-/day in a population of African patients with symptomatic HIV infection. (Sex Transm Inf 1998;74:265-270)

Antiretroviral Drugs Alter the Content of Extracellular Vesicles from HIV-1-Infected Cells

“…However, treatment of HIV-1-infected patients with IFNα, with and without concurrent cART, has resulted in conflicting outcomes in vivo . Positive response to the treatment is moderate while poor responses, including lack of tolerance and disease progression, can occur 53 – 57 . It has been speculated that IFN treatment for HIV-1 infection may be most beneficial in early infection and therefore requires further mechanistic investigation 50 .…”

HIV-1 Promotes the Degradation of Components of the Type 1 IFN JAK/STAT Pathway and Blocks Anti-viral ISG Induction

“…However, responses to treatment were variable, with higher baseline CD4 T cell counts being associated with better clinical response and greater decline in viral load. While these clinical benefits were modest and some decline in viral load was observed in several studies, the decrease was limited in magnitude (typically 0.5 to 1 log), and was not sustained ( Katabira et al, 1998 ; Vento et al, 1993 ; Soriano et al, 1994 ; Sperber et al, 1993 ; Fischl, 1991 ; Skillman et al, 1996 ; Hatzakis et al, 2001 ; Asmuth et al, 2010 ; Manion et al, 2012 ). More recent studies have tested the effects of pegylated-IFN-α upon HIV control during structured ART interruptions.…”

Modulation of HIV-1 Transcription by Cytokines and Chemokines

“…Early trials of IFNα did not report clinical benefits or adverse effects for treatment with this cytokine [164][165][166][167][168]. Treatment of HIV-1 infected patients with an IFNα vaccine, however, did result in lower rates of progression to disease, although these rate changes were not statistically significant [169].…”