Administration of Imiquimod, an Interferon Inducer, in Asymptomatic Human Immunodeficiency Virus‐Infected Persons to Determine Safety and Biologic Response Modification

Abstract

A phase I study to determine safety, maximum tolerated dose, and biologic response during multiple once-a-week administration of oral imiquimod, an immune response modifier, was conducted in 12 adults with early human immunodeficiency virus (HIV) infection. All completed the dose-escalation phase of weekly dosing at 100-mg increments and received at least one maintenance dose, 100 mg below the patient's toxic dose, for 12 weeks. Dose-limiting toxicity occurred in 3 patients at 200-mg, 5 at 300-mg, and 3 at 400-mg dose levels. One tolerated the 500-mg dose without dose-limiting toxicity. Dose-limiting toxicities included fatigue, fever, malaise, increased transaminases, hypotension, vomiting, and depression. Seven of 12 completed 12 weeks of maintenance. At > or = 200 mg of imiquimod, all patients had biologic responses, measured by elevations in serum interferon, beta2-microglobulin, and neopterin levels. Imiquimod induced pronounced levels of circulating interferon in asymptomatic HIV-infected persons, with variable effect on virus load.

Cancer immunotherapeutic potential of novel small molecule TLR7 and TLR8 agonists

“…Until now, TLR7 and TLR8 agonists were predominantly administered topically due to the side effects reported after oral and systemic therapy (i.e., with imiquimod) (Goldstein et al, 1998). Systemic administration with resiquimod was even associated with transient peripheral blood leukocyte depletion (Gunzer et al, 2005).…”

Results of a Phase 1 Dose Escalation Study of Intravesical TMX-101 in Patients with Nonmuscle Invasive Bladder Cancer

“…This value is still below plasma values observed after oral intake (100 mg) or subcutaneous administration (30 mg) of imiquimod that were not associated with toxicities (123 and 128 ng/ml, respectively). 28,29 A limitation of our study is the availability of pharmacokinetic data for only 1 patient per dose group. Because of ethical considerations and patient burden, blood sampling for pharmacokinetics until 6 hours after the instillation was only allowed in 1 patient per group.…”

An investigator-initiated study to assess the safety and efficacy of imiquimod 3.75% cream when used after cryotherapy in the treatment of hypertrophic actinic keratoses on dorsal hands and forearms

“…16,17 Systemic adverse events are rare, as systemic absorption is reportedly seen in a minority of cases (<1%). 18,19 The majority of these reported AEs include influenza-like or gastrointestinal symptoms or induction of nondermatological disorders. 20,21 This rare systemic response is thought to occur because imiquimod induces cytokines in the area of application and can potentially cause systemic augmentation of the immune response.…”