Low-dose oral natural human interferon-α in 29 patients with HIV-1 infection

Kaiser, G.; Jaeger, Hans; Birkmann, Josef; Poppinger, Josef; Cummins, Josef M.; Gallmeier, W. M.

doi:10.1097/00002030-199206000-00007

Cited by 25 publications

(6 citation statements)

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“…13 Subsequent small studies failed to substantiate these spectacular claims. [14][15][16] In September 1990, the World Health Organisation (WHO) called a meeting of researchers, representatives of national drug regulatory agencies, and pharmaceutical manufacturers to examine the conflicting evidence on the eYcacy of low dose oral IFN-. The data presented at this meeting were not conclusive and the expert committee recommended that WHO should commission a randomised double blind placebo controlled study of suYcient sample size to establish whether low dose oral IFN-was eYcacious in the treatment of symptomatic HIV infection.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1998

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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)

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Section: Introductionmentioning

confidence: 99%

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

et al. 1998

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“…Low-dose oromucosal HuIFNα has been tested for effects in 22 clinical trials of HIV+ patients [75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96]. Weight gain, relief from opportunistic infections and stabilization and/or improvement in blood profiles (CD4+ cell counts, in particular) have been reported as positive benefits of oromucosal HuIFNα therapy in 12 of the 20 studies in which HIV+ symptomatic patients were enrolled and clinical effects were monitored [75,76,77,78,79,83,85,88,90,91,94,96].…”

Section: Oromucosal Ifn Therapy In Human Immunodeficiency Virus (Hiv)mentioning

confidence: 99%

“…In these studies, different sources of HuIFNα and different doses and schedules were tested. In general, African or African-American HIV+ patients [75,76,77,78,79,87,88,90,94] responded more positively to oromucosal administration of HuIFNα than did other HIV+ ethnic groups including Germans [80], Canadians [81,82], Philippinos [86], or Americans [91,93,95]. The reasons for the differences in response to oromucosal HuIFNα when used in Africa versus Europe or North America are unknown but could be related to race, diet and/or concomitant indigenous infections, such as malaria.…”

Section: Oromucosal Ifn Therapy In Human Immunodeficiency Virus (Hiv)mentioning

confidence: 99%

“…The reasons for the differences in response to oromucosal HuIFNα when used in Africa versus Europe or North America are unknown but could be related to race, diet and/or concomitant indigenous infections, such as malaria. It is important to note that some human HIV-treatment studies with oromucosal HuIFNα have reported no beneficial effects [80,81,82,86,91,93,95]. …”

Section: Oromucosal Ifn Therapy In Human Immunodeficiency Virus (Hiv)mentioning

confidence: 99%

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Oromucosal Administration of Interferon to Humans

et al. 2010

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The prevailing dogma is that, to be systemically effective, interferon-alpha (IFNα) must be administered in sufficiently high doses to yield functional blood concentrations. Such an approach to IFNα therapy has proven effective in some instances, but high-dose parenteral IFNα therapy has the disadvantage of causing significant adverse events. Mounting evidence suggests that IFNα delivered into the oral cavity in low doses interacts with the oral mucosa in a unique manner to induce systemic host defense mechanisms without IFNα actually entering the circulation, thus reducing the potential for toxic side effects. A better understanding of the applications and potential benefits of this treatment modality are under active investigation. This paper provides a review of the relevant literature on the clinical use of the oromucosal route of administration of interferon, with an emphasis on the treatment of influenza.

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“…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].…”

Section: Immune Based Therapy In Hiv Infectionmentioning

confidence: 99%

Modulation of HIV-1 Transcription by Cytokines and Chemokines

Copeland¹

2005

MRMC

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Infection with HIV results in the modulation of circulating levels of many host factors. Several host proteins that are up-regulated in HIV infection have the potential to influence virus replication. More specifically, the transcription of HIV-1 can be modulated in vivo by host proteins, including cytokines and chemokines. Cytokines modulate transcription mediated by the HIV-1 long terminal repeat (LTR) via multiple signal transduction pathways with resulting recruitment of numerous transcription factors, including NFkappaB, C/EBP, AP-1, TCF-1alpha, NF-IL-6 and ISGF-3. The effects on transcription may vary depending upon the cell type studied and upon the timing of the exposure of infected or transfected cells to cytokines. Furthermore, studies of cytokine mediated activation or inhibition of LTR mediated transcription may also be affected by the presence of the HIV-1 trans-activating protein, Tat, which has significant impact upon the redox state of the cell. This review will examine the complexities of the positive and negative control of HIV transcription by cytokines and chemokines.

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Low-dose oral natural human interferon-α in 29 patients with HIV-1 infection

Cited by 25 publications

References 0 publications

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

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

Oromucosal Administration of Interferon to Humans

Modulation of HIV-1 Transcription by Cytokines and Chemokines

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