Acyclovir Therapy for Mucocutaneous Herpes Simplex Infections in Immunocompromised Patients

101

ACV is an effective agent for the treatment and prophylaxis of HSV infections in both IC and immunologically normal individuals. The drug is well tolerated in both populations and is not significantly associated with clinical or laboratory toxicities. Because of the great potential benefit and low risk, organ transplant recipients and patients with hematologic malignancies undergoing induction chemotherapy should be screened routinely for HSV antibodies; seropositive individuals should receive prophylactic ACV during the period of most profound immunosuppression. Immunologically normal individuals with frequently recurring genital HSV or serious complications associated with outbreaks are candidates for long-term suppression with ACV.

Section: Suppressive Acv In Ic Patientsmentioning

confidence: 99%

Acyclovir prophylaxis for herpes simplex virus infection

Gold¹,

Corey²

1987

101

“…In addition, ACV is phosphorylated selectively to an active form in virus-infected cells and is nontoxic to uninfected mammalian cells over a wide range of concentrations (22). The value of ACV applied intravenously, orally, and topically in the treatment of severe HSV infections in immunosuppressed hosts and in primary genital HSV infections has been documented (5,7,15,25,27). However, the results of treatment of recurrent mucocutaneous HSV infections in normal subjects with topical 5% ACV in polyethylene glycol (PEG; Zovirax) were disappointing.…”

mentioning

confidence: 99%

Penetration of guinea pig skin by acyclovir in different vehicles and correlation with the efficacy of topical therapy of experimental cutaneous herpes simplex virus infection

Spruance¹,

McKeough²,

Cardinal³

1984

Inadequate penetration of antiviral agents through the stratum corneum of the skin may be one of the limiting factors in the topical therapy of recurrent cutaneous herpes simplex virus infections in humans. In vitro studies of the penetration of the nucleoside analog acyclovir (ACV) through guinea pig skin demonstrated a marked increase in drug flux when ACV was formulated in dimethyl sulfoxide (DMSO), compared with water or polyethylene glycol (PEG) as the vehicle. To examine whether the increased transcutaneous flux of ACV effected by DMSO was meaningful in vivo, topical 5% ACV in DMSO was evaluated for the treatment of cutaneous herpes simplex virus infection in guinea pigs and compared with topical 5% ACV in PEG. When compared with infection sites treated with the vehicle alone, ACV in DMSO produced a greater percent reduction than did ACV in PEG in median lesion number (8 versus 58%; P < 0.001), median lesion area (35 versus 73%; P = 0.001), and median lesion virus titer (21 versus 84%; P = 0.08). We conclude that DMSO is a highly effective vehicle for topical administration of ACV and is superior to PEG in our model. Careful choice of vehicle and consideration of transcutaneous penetration may be important for realization of the full potential of topical antiviral therapy in humans.Development of an effective topical therapy for recurrent mucocutaneous herpes simplex virus (HSV) infections in immunologically normal humans has been difficult (16). Acyclovir (ACV) is a new anti-herpesvirus compound which is 10-to 150-fold more potent in vitro than older drugs such as vidarabine or iodoxuridine (IDU). In addition, ACV is phosphorylated selectively to an active form in virus-infected cells and is nontoxic to uninfected mammalian cells over a wide range of concentrations (22). The value of ACV applied intravenously, orally, and topically in the treatment of severe HSV infections in immunosuppressed hosts and in primary genital HSV infections has been documented (5,7,15,25,27). However, the results of treatment of recurrent mucocutaneous HSV infections in normal subjects with topical 5% ACV in polyethylene glycol (PEG; Zovirax) were disappointing. Topical treatment of recurrent herpes simplex labialis and recurrent herpes genitalis effected a reduction in the excretion of virus from the lesions, but there was no change in the clinical course of infection (7, 24).Assessment of the reasons for the clinical failure of topical ACV therapy in the treatment of recurrent herpes labialis and genitalis has led to the conclusion that either ACV was applied too late to affect the natural course of recurrent HSV disease or that it did not penetrate the stratum corneum and reach infected cells in the lower layers of the epidermis in adequate concentrations (24). To evaluate the latter possibility, we studied the flux of ACV through guinea pig skin in vitro from different drug vehicles and have compared these findings with the in vivo efficacy of two drug vehicle combinations in the topical treatment of an experimental HSV in...

“…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

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...