Oral Acyclovir in the Treatment of Genital Herpes. Preliminary Report of a Multicenter Trial

Fiddian, A P; Halsos, A M; Kinge, Bettina; Nilsen, Arvid; Wikstrom, K.

doi:10.1016/s0022-5347(17)52142-4

Cited by 6 publications

(8 citation statements)

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“…Each of these compounds was initially shown to be an effective inhibitor of herpes simplex virus (HSV) and has been used to treat HSV infections (4,5,10,13,23). However, due to problems of low therapeutic indices and isolation of HSV resistant to these antiviral agents, studies have been undertaken to examine the potential of polychemotherapy in the treatment of HSV infections.…”

mentioning

confidence: 99%

Synergistic antiviral activity of acyclovir and interferon on human cytomegalovirus

Smith¹,

Wigdahl²,

Rapp³

1983

Antimicrob Agents Chemother

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The efficacy of human alpha interferon (IFN-a) combined with 9-(2'-hydroxyethoxymethyl)guanine (acyclovir; ACV), (E)-5-(2-bromovinyl)-2'-deoxyuridine, 9-0-D-arabinofuranosyladenine, or 1-0-D-arabinofuranosylcytosine on the inhibition of human cytomegalovirus (HCMV) replication in human embryonic lung cells was analyzed by plaque reduction assays. IFN-a combined with 9-,B-Darabinofuranosyladenine or 1-,B-D-arabinofuranosylcytosine produced an additive antiviral activity with respect to HCMV plaque formation. IFN-a combined with (E)-5-(2-bromovinyl)-2'-deoxyuridine also exhibited additive antiviral activity. However, IFN-a combined with ACV at concentrations higher than 10 ,uM consistently yielded synergistic activity in HCMV plaque reduction assays. Kinetic analyses of HCMV replication demonstrated that approximately a 1,000-fold reduction can be attained through the synergistic interaction between ACV (200 ,uM) and IFN-a (42 IU/ml). These data suggest that combined ACV and IFNa treatment may be useful against HCMV infection.Human cytomegalovirus (HCMV) has been implicated in a wide range of clinical diseases, including intrauterine infections, perinatal infections, infections of immunosuppressed transplant and cancer patients, birth defects, and, more recently, acquired immunodeficiency disease syndrome and Kaposi sarcoma (2,14,20,24). In general, treatment of HCMV with 1-P-Darabinofuranosylcytosine (ara-C [25]), 9-P-Darabinofuranosyladenine (ara-A [19]) or human alpha interferon (IFN-a [21]) has not been successful. In addition, the newly licensed drug 9-(2'-hydroxyethoxymethyl)guanine (acyclovir; ACV) has not been effective in the treatment of HCMV pneumonia (32).Each of these compounds was initially shown to be an effective inhibitor of herpes simplex virus (HSV) and has been used to treat HSV infections (4, 5, 10, 13, 23). However, due to problems of low therapeutic indices and isolation of HSV resistant to these antiviral agents, studies have been undertaken to examine the potential of polychemotherapy in the treatment of HSV infections. Combination therapy has proven to be effective against bacterial infections and certain cancers (9, 26) and may allow decreased dosage and duration of treatment, thus reducing toxicity and the incidence of resistant virus strains.Numerous in vitro studies have examined the type of interaction (additive, synergistic, or antagonistic) of various antiherpetic compounds when used in combination. Ara-A in combination with human beta interferon (IFN-P [3]) or ACV (27) has been shown to have an additive inhibitory effect on HSV replication. Synergistic inhibitory interactions have been reported with ara-A in combination with IFN-a (16) or (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU [27]). ACV combined with IFN-a (17) or has also been shown to have a synergistic inhibitory effect on HSV replication. However, the combined interaction of ACV with BVDU has been shown to be only additive (27). ACV in combination with BVDU has also been demonstrated to have only an additive inhibitory e...

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mentioning

confidence: 99%

Synergistic antiviral activity of acyclovir and interferon on human cytomegalovirus

Smith¹,

Wigdahl²,

Rapp³

1983

Antimicrob Agents Chemother

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“…By contrast, oral administration of ACV more effectively reduces genital lesions (9), and more recent studies in which ACV was administered orally to prevent herpetic lesion recurrence indicate that this prophylactic treatment approach may be highly effective (3). The limited solubility of ACV has resulted in reversible renal disturbances after bolus injection (2) and may, in part, be responsible for the poor absorption after oral administration (6).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of 2'-nor-2'-deoxyguanosine treatment for orofacial herpes simplex virus type 1 skin infections in mice

Davies¹,

Bondì²,

Field³

1984

Antimicrob Agents Chemother

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2'-Nor-2'-deoxyguanosine (2'NDG), a new antiviral agent, conferred protection when given orally or topically to hairless mice after the mice were subjected to orofacial infection with herpes simplex virus type 1. The average severity of orofacial lesions was significantly reduced in mice receiving oral gavage treatments twice daily for 7 days beginning 3 h postinfection. The minimum effective dose of 2'NDG was 0.2 mg/kg per day. A minimum of eight treatments over 4 days resulted in a significant reduction in lesion severity. Topical treatment begun 3 h postinfection and continued four times daily for 3 days resulted in a minimum effective dose of 0.06%. Oral treatment with 2'NDG begun as late as 72 h postinfection or topical treatment begun as late as 48 h postinfection resulted in significantly reduced lesion severity compared with lesion severity among placebo-treated animals. In addition, significant prevention of ganglionic infection occurred when 2'NDG was administered either orally or topically within 24 h after infection.

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“…91 Heat-killed whole virus vaccines including HSV-2 (Lupidon G) and HSV-1 (Lupidon H) are efficacious in 80% of patients with negligible adverse events. 92 Doubleblind, placebo-controlled clinical trials report a decrease in the number and duration of yearly recurrences and First line Oral acyclovir Baker 147 Blom et al 148 Braig et al 149 Bryson 150 Bryson et al 151 Douglas et al 152 Fiddian et al 153 Goldberg et al 154 Goldberg et al 155 Gupta et al 156 Halsos et al 157 Kaplowitz et al 158 Kinghorn et al 159 Kroon et al 160 Mertz et al 161 Mertz et al 162 Mindel et al 163 Mindel et al 164 Nilsen et al 165 Reichman et al 166 Reichman et al 167 Ruhnek-Forsbeck et al 168 Sacks et al 169 Scott et al 115 Straus et al 170 Thin et al 171 Velasco et al 172 Wald et al 45 Watts et al 114…”

Section: Immunotherapeutic Hsv-2 Vaccinesmentioning

confidence: 99%

Herpes simplex virus and human papillomavirus genital infections: new and investigational therapeutic options

et al. 2010

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Human papillomavirus and Herpes simplex virus are the most common genital viral infections encountered in clinical practice worldwide. We reviewed the literature focusing on new and experimental treatment modalities for both conditions, based on to the evidence-based data available. The modalities evaluated include topical agents such as immune response modifiers (imiquimod, resiquimod, and interferon), antivirals (penciclovir, cidofovir, and foscarnet), sinecatechins, microbiocidals (SPL7013 gel, and PRO 2000 gel), along with experimental (oligodeoxynucleotides), immunoprophylactic, and immunotherapeutic vaccines.

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Oral Acyclovir in the Treatment of Genital Herpes. Preliminary Report of a Multicenter Trial

Cited by 6 publications

References 0 publications

Synergistic antiviral activity of acyclovir and interferon on human cytomegalovirus

Synergistic antiviral activity of acyclovir and interferon on human cytomegalovirus

Efficacy of 2'-nor-2'-deoxyguanosine treatment for orofacial herpes simplex virus type 1 skin infections in mice

Herpes simplex virus and human papillomavirus genital infections: new and investigational therapeutic options

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