Long-term Acyclovir Suppression of Frequently Recurring Genital Herpes Simplex Virus Infection

Mertz, Grégory; Jones, Clifton C.; Mills, John; Fife, Kenneth H.; Lemon, Stanley M.; Stapleton, Jack T.; Hill, Edward C.; Davis, L. Gray

doi:10.1001/jama.1988.03410020067030

Cited by 142 publications

(19 citation statements)

References 18 publications

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“…While effective, this approach requires chronic daily dosing to maintain inhibition of the virus, demands good compliance, and is expensive (14,15,17,18,19). There is no posttreatment efficacy; discontinuation of suppressive treatment results in reversion to the pretreatment recurrence rate (6,23).…”

mentioning

confidence: 99%

Imiquimod 5-Percent Cream Does Not Alter the Natural History of Recurrent Herpes Genitalis: a Phase II, Randomized, Double-Blind, Placebo-Controlled Study

Schacker

Conant

Thoming

et al. 2002

Antimicrob Agents Chemother

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Present strategies for control of herpes genitalis recurrences require multiple daily doses of antiviral medication. Imiquimod, an immune response modifier, induces alpha interferon and interleukin-12; application in the presence of local herpes antigens during a recurrence may augment herpes simplex virus (HSV)-specific cell-mediated immunity. To test this theory, we performed a randomized, double-blind, placebocontrolled study of imiquimod 5% cream to assess safety and efficacy for decreasing recurrences. Patients with six or more recurrences of herpes genitalis per year applied study cream (imiquimod or placebo) to lesions one, two, or three times per week for 3 weeks for each recurrence during a 16-week treatment period. This was followed by a 16-week observation period. Of 124 patients randomized to the study, 103 completed the treatment period and 93 completed the observation period. The median times to first genital herpes recurrence were 53 days for those receiving placebo (n ‫؍‬ 30) and 54, 60, and 64 days for those receiving imiquimod one time per week (n ‫؍‬ 34), two times per week (n ‫؍‬ 32), and three times per week (n ‫؍‬ 28), respectively. The median annualized recurrence rates during the treatment period were 3.8, 4.9, 3.2, and 3.1, respectively. There were no statistically significant differences in the time to first recurrence or in the annualized recurrence rate between the imiquimod and placebo groups in either the treatment or the observation period. A trend in increased rates of local adverse events at the application site and a delay in lesion healing with more frequent dosing suggested a pharmacologic effect. Although clinical efficacy has been observed for imiquimod in other conditions in which a TH1-type immune response may be beneficial, including other viral infections such as those caused by human papillomavirus, no apparent effect on the short-term natural history of herpes genitalis recurrences was observed.

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confidence: 99%

Imiquimod 5-Percent Cream Does Not Alter the Natural History of Recurrent Herpes Genitalis: a Phase II, Randomized, Double-Blind, Placebo-Controlled Study

Schacker

Conant

Thoming

et al. 2002

Antimicrob Agents Chemother

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“…This study also found that !10% of persons seropositive for HSV-2 reported a history of genital lesions [4]. Antiviral drug therapy shortens the severity and duration of lesions and reduces recurrences [5,6]. However, antiviral drug therapy is not applicable to prophylaxis and, although it is effective for the treatment of asymptomatic disease [7], its need may go unrecognized in this population, exacerbating the spread of disease.…”

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confidence: 99%

Plasmid DNA–Expressed Secreted and Nonsecreted Forms of Herpes Simplex Virus Glycoprotein D2 Induce Different Types of Immune Responses

Higgins

Herold²,

Arnold

et al. 2000

J INFECT DIS

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Herpes simplex viruses (HSVs) are significant pathogens and major targets of vaccine development. Several attempts have been made to develop prophylactic and therapeutic vaccines for HSV types 1 and 2. Although these vaccines elicit strong humoral responses, the overall impact on pathology has been disappointing. An effective vaccine for HSV must induce both humoral and cellular immune responses. DNA vaccines are ideal candidates for HSV vaccines because they induce both types of immune responses. This study showed that the type of immune response generated by immunization with DNA vaccines is modulated by expression of various forms of an antigen, each with a different cellular localization. Expression of cell-associated forms of HSV-2 glycoprotein D (gD) induces primarily a Th1 response, whereas expression of secreted gD results in a Th2 response. Immunization with plasmids expressing different forms of the antigen may increase the efficacy of a vaccine.

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“…The efficacy of acyclovir for the treatment and suppression of anogenital herpes simplex virus (HSV) infections has been established in placebo-controlled trials (4,5,7). Despite estimates of the prevalence of acyclovir-resistant mutants within mucocutaneous herpetic lesions which range from 0 to 6.2% in untreated immunocompetent patients (1,3), cutaneous healing has generally been unimpeded in these hosts.…”

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confidence: 99%

Correlation between response to acyclovir and foscarnet therapy and in vitro susceptibility result for isolates of herpes simplex virus from human immunodeficiency virus-infected patients

Safrin

Elbeik

Phan

et al. 1994

Antimicrob Agents Chemother

104

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In vitro susceptibility testing of herpes simplex virus (HSV) isolates will play an increasingly important role in guiding the clinical management of immunocompromised hosts who have lesions that are poorly responsive to therapy with standard antiviral agents. We assessed the correlation between the in vitro susceptibility result using a plaque reduction assay in Vero cells and the response to antiviral therapy with acyclovir or foscarnet for 243 clinical isolates of HSV collected from 115 human immunodeficiency virus-infected patients. The in vitro results and clinical responses were highly associated for both acyclovir and foscarnet (P < 0.001 and P < 0.001, respectively). The predictive values of a susceptible result (50% elfective concentrations, <2 ,ug/ml for acyclovir and <100 ,ug/ml for foscarnet) for complete healing of lesions were 62% for acyclovir and 82% for foscarnet; the predictive values of a resistant result for failure to heal were 95% for acyclovir and 88% for foscarnet. Thus, in vitro testing has clinical utility in guiding therapy, although the 1 to 2 weeks required to derive a definitive result by the plaque reduction assay is a major limitation.

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Long-term Acyclovir Suppression of Frequently Recurring Genital Herpes Simplex Virus Infection

Cited by 142 publications

References 18 publications

Imiquimod 5-Percent Cream Does Not Alter the Natural History of Recurrent Herpes Genitalis: a Phase II, Randomized, Double-Blind, Placebo-Controlled Study

Imiquimod 5-Percent Cream Does Not Alter the Natural History of Recurrent Herpes Genitalis: a Phase II, Randomized, Double-Blind, Placebo-Controlled Study

Plasmid DNA–Expressed Secreted and Nonsecreted Forms of Herpes Simplex Virus Glycoprotein D2 Induce Different Types of Immune Responses

Correlation between response to acyclovir and foscarnet therapy and in vitro susceptibility result for isolates of herpes simplex virus from human immunodeficiency virus-infected patients

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