Interferon in the prevention of genital herpes recurrence

Abstract

Patients with genital herpes were treated three times weekly for 12 weeks with 3 x 106 IU of alpha2b interferon (20 patients) or placebo (17 patients) administered by subcutaneous injection in a double-blind trial. Interferon had minimal effects on the suppression of recurrences and moderate toxicity (chills, fever, fatigue, and leukopenia), suggesting that this route and dosage of interferon may not be clinically useful for this indication.Genital herpes establishes latency in the sacral nerve following a primary attack and recurs in 80 to 90% of patients (1). Attempts to prevent these recurrences with daily administration of oral acyclovir have been successful. However, this drug is not curative, so that when therapy is terminated, the outbreaks recur at their original frequency (2, 11). In addition, the possibility of the emergence of acyclovirresistant viruses has prompted the search for other antiviral agents effective for this indication.Human alpha interferon possesses antiviral and immuneenhancing properties. Its availability in large quantities owing to recombinant genetic technology has allowed clinical trials to test its usefulness in the therapy of genital herpes. However, it proved to be ineffective in shortening the duration of virus shedding or the time of healing of a recurrence when compared with a placebo (3). We hoped that it might be effective in genital herpes when used prophylactically to prevent recurrences, as it prevented the reactivation of herpes simplex after sectioning of the trigeminal root (9), reactivation of cytomegalovirus in transplant recipients (6), and transmission of rhinovirus (4). Therefore, we undertook a placebo-controlled, double-blind evaluation of recombinant alpha2b interferon in the prevention of frequent recurrences of genital herpes.( Patients were also examined by questioning and by evaluation of a complete blood count, routine blood chemistries, and urinalysis for drug toxicity at the end of week 1 of therapy and monthly while receiving medication. They were also tested for the development of neutralizing factors to interferon before and after therapy. Statistical analyses were performed by survival analysis with the Mantel-Cox method (time to healing, duration of virus shedding, and time to first recurrence), by a Wilcoxon two-sample test (recurrence rate), and by Fisher's exact test (number of patients without recurrence). The duration of virus shedding was defined as the time from the first positive culture to the first negative culture, time to healing was defined as the time to the epithelialization of all lesions, and time to first recurrence was defined as the time from the initiation of therapy to the appearance of the first herpetic lesion.A total of 37 patients (17 males and 20 females) with recurrences of genital herpes were enrolled in this study. Twenty received interferon, and seventeen received a placebo. Two of the interferon patients dropped out of the study after 3 weeks of therapy because of side effects. All groups were comparable with r...

Effects of the immunomodulating agent R837 on acute and latent herpes simplex virus type 2 infections

“…Alpha interferon (human) was also effective in guinea pigs when it was given prophylactically or shortly (0.5 h) after inoculation but not at 24 h after inoculation with HSV type 1 (15). Similarly, alpha interferon (11,12) and inosine pranobex, an immune modifier (21,22), have been disappointing for the treatment of genital HSV infections in humans. When muramyl tripeptide-phosphatidylethanolamine, another biologic response modifier, was evaluated in the guinea pig model of genital herpes infection, only moderate effects were seen, even when it was given prophylactically (10).…”

Therapy of genital herpes with topically applied interferon

“…Four of eighteen (22%) high-dose interferon recipients experienced gastrointestinal symptoms (nausea and diarrhea), whereas only one low-dose interferon recipient (5%) and no placebo recipients experienced these symptoms (P < 0.05 by Cochran-Mantel-Haenszel chi-square). (6,7). However, at least one study (10) has demonstrated some efficacy in genital herpes, and others (3,4,8,16) Inc.), increases in the levels of interferon in serum were not detected in our patients treated with alpha-2a interferon (data on file; Hoffmann-La Roche Inc.).…”