Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial.

Hann, Ian; Prentice, H. G.; Blacklock, Hilary; Ross, M. G. R.; Brigden, D.; Rosling, Ari; Burke, Colin; Crawford, D. H.; Brumfitt, W.; Hoffbrand, A. V.

doi:10.1136/bmj.287.6389.384

Cited by 140 publications

(58 citation statements)

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“…T his study also contirms that both intravenous and oral acyclovir can significantly reduce the Months since transplant rate of infections with HSV after allogeneic bone marrow ---Control -6 Month ACV transplantation. This has been previously shown by others (Wade et al, 1984;Gluckman et al, 1983;Saral et al, 1981; Acyclovir prophylaxis study Hann et al, 1983;Shepp et al, 1987). Meyers et al (1988) have observed a reduction in CMV infection in patients given larger doses of acyclovir (500 mg m -2) compared to a concurrent, non-randomised, control group.…”

Section: Discussionsupporting

confidence: 62%

The prophylactic role of intravenous and long-term oral acyclovir after allogeneic bone marrow transplantation

Selby

Powles²,

Easton³

et al. 1989

Br J Cancer

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Summary Eighty-two patients were randomly allocated to receive intravenous acyclovir 5 mg kg 1t.d.s. for 23 days followed by oral acyclovir 800mg 6-hourly for 6 months or matching placebos after allogeneic bone marrow transplantation. Herpes simplex and varicella zoster virus infections were significantly reduced during the period of administration of acyclovir. No reduction in cytomegalovirus infection was demonstrated. The drug was not toxic.The introduction of acyclovir into clinical practice was a useful development in the management of herpesvirus infections (Selby et al., 1979). The drug has been proved to be a highly effective treatment for herpes simplex (HSV) and varicella zoster virus (VZV) infections both in immune compromised and immune competent patients (Meyers et al., 1982;Balfour et al., 1983;Prober et al., 1982; reviewed by Fiddian & Grant, 1985;Prentice & Hann, 1985;Strauss, 1985;Gore & Selby, 1987). The efficacy and lack of toxicity of acyclovir has led to its use to prevent reactivation of herpesvirus infections. It is effective in the prophylaxis of HSV reactivation both in the immune competent patient with, for instance, recurrent genital herpes simplex and in the immune compromised patient, after, for instance, allogeneic bone marrow transplantation (Saral et al., 1981;Gluckman et al., 1983;Wade, 1984; Fiddian & Grant, 1985;Prentice & Hann, 1985; Straus, 1985;Gore & Selby, 1987). However, information about the prophylaxis of VZV infection is much less complete.The concentrations of acyclovir that are required to inhibit VZV in vitro are much higher than those required to inhibit HSV. This observation, together with the limited absorption of acyclovir when given by the oral route (Brigden & Whiteman, 1985), led to doubt about the effectiveness of acyclovir for the oral treatment or prophylaxis of VZV. However, it has been shown that oral acyclovir in high doses is effective in shortening the duration of VZV infections in immune competent patients (Peterslund, 1985;McKendrick et al., 1986).Reactivation of both HSV and VZV after bone marrow transplantation are a common source of morbidity. Up to 70% of patients who are seropositive for HSV infection develop reactivations and 40% of patients get herpes zoster or varicella (Saral et al., 1981;Locksley et al., 1985). However, evidence that long-term oral acyclovir will prevent the development of VZV was inconclusive. We have therefore carried out a prospective randomised double blind trial of intravenous acyclovir given for 23 days followed by oral acyclovir for 6 months in patients following allogeneic bone marrow transplantation. (Freedman & White, 1976).Acyclovir or placebo was administered to adults at a dose of 5mg kg-1 in 100 ml of normal saline infused over 1 h, given 8-hourly starting on the day before transplantation and continuing for 23 days. At that point adults received 800mg tablets 6-hourly for 6 months. Children less than 12 years of age received 250 mg m-2 acyclovir intravenously followed by 400mg orally 6-hourly. Patients wer...

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Section: Discussionsupporting

confidence: 62%

The prophylactic role of intravenous and long-term oral acyclovir after allogeneic bone marrow transplantation

Selby

Powles²,

Easton³

et al. 1989

Br J Cancer

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“…More importantly they cause dysphagia leading to inadequate food and fluid intake in patients who are often very ill and have a high metabolic rate. They may also act as a portal of entry for micro-organisms causing secondary infections (Lundgren et al, 1985) which in turn may delay reconstitution of the bone marrow and hence prolong the period of neutropenia (Hann et al, 1983).…”

mentioning

confidence: 99%

Herpes simplex in oral ulcers in neutropenic patients

Jan-Mohamed¹,

Morton²,

Milligan³

et al. 1990

Br J Cancer

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“…In the past year eight of 25 (32%) patients with non-Hodgkin's lymphoma, admitted to our oncology ward with pyrexia when neutropenic, had virologically confirmed HSV infections. Intravenous acyclovir has been shown in randomised, placebo controlled trials to be effective in the treatment of HSV infection in immunocompromised patients (Chou et al, 1981;Mitchell et al, 1981;Wade et al, 1982), and in the prophylaxis of HSV infection (Hann et al, 1983;Saral et al 1981). A report of oral acyclovir prophylaxis in bone marrow transplant patients has shown a reduced incidence of HSV in those patients treated with acyclovir compared with placebo, without significant toxicity (Gluckman et al 1983).…”

mentioning

confidence: 99%

Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. A randomised double blind, placebo controlled trial

Anderson¹,

Scarffe²,

Sutton³

et al. 1984

Br J Cancer

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Summary Forty-one patients receiving remission induction chemotherapy with vincristine, adriamycin and prednisolone (VAP) for high grade lymphoma or acute lymphoblastic leukaemia were entered into a double blind, placebo controlled trial of oral acyclovir prophylaxis against herpes simplex virus (HSV) infection. The dose of acyclovir was 200mg four times daily for the duration of chemotherapy (six weeks). Of the 40 evaluable patients, 20 were randomised to each arm. Prophylactic oral acyclovir significantly reduced the incidence of clinical HSV infection from 60% on placebo to 5% acyclovir (P<0.001), and the incidence of viral isolates from 70% on placebo to 5% on acyclovir (P<0.001).Herpetic infections are common in immunosuppressed patients with malignant diseases (Aston et al., 1972;Casazza et al., 1966;Lam et al., 1981;Meyers et al., 1980;Muller et al., 1972), and may be life threatening. The oral ulceration and stomatitis caused by HSV may be associated with significant morbidity. In the past year eight of 25 (32%) patients with non-Hodgkin's lymphoma, admitted to our oncology ward with pyrexia when neutropenic, had virologically confirmed HSV infections. Intravenous acyclovir has been shown in randomised, placebo controlled trials to be effective in the treatment of HSV infection in immunocompromised patients (Chou et al., 1981;Mitchell et al., 1981;Wade et al., 1982), and in the prophylaxis of HSV infection (Hann et al., 1983;Saral et al. 1981). A report of oral acyclovir prophylaxis in bone marrow transplant patients has shown a reduced incidence of HSV in those patients treated with acyclovir compared with placebo, without significant toxicity (Gluckman et al. 1983). The aim of this trial was to evaluate the efficacy of prophylactic oral acyclovir against HSV infections in lymphoma and leukaemia patients receiving remission induction chemotherapy, in a double blind placebo controlled trial. Patients and methodsForty-one patients with high grade non-Hodgkin lymphoma or acute lymphoblastic leukaemia who were to receive chemotherapy using the VAP regimen (Blackledge et al., 1980) (Vincristine 2mg intravenously weekly for six weeks, Adriamycin 60 mgm-2 intravenously fortnightly for three doses, and oral prednisolone at 50 mg day-1 for six weeks)were eligible for the trial. After obtaining informed consent patients were randomised to receive acyclovir 200mg four times daily or placebo tablets of identical appearance. The tablets commenced on the first day of chemotherapy and were prescribed for six weeks.Patients with non-Hodgkin lymphoma attended the outpatient clinic for examination and treatment each week, and those with acute leukaemia were inpatients for the duration of therapy. Throat swabs and blood samples for haematology, biochemistry and acyclovir levels were taken weekly. Blood for viral serology was taken every three weeks. At each outpatient visit patients were asked about oral symptoms and coldsores. Lesions present at the time of consultation were swabbed for viral culture and if applicable sa...

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Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial.

Cited by 140 publications

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The prophylactic role of intravenous and long-term oral acyclovir after allogeneic bone marrow transplantation

The prophylactic role of intravenous and long-term oral acyclovir after allogeneic bone marrow transplantation

Herpes simplex in oral ulcers in neutropenic patients

Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. A randomised double blind, placebo controlled trial

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