Resistance of Herpes Simplex Virus Infections to Nucleoside Analogues in HIV‐Infected Patients

Levin, Myron J.; Bacon, Teresa H.; Leary, Jeffry J.

doi:10.1086/422364

Cited by 118 publications

(129 citation statements)

References 89 publications

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“…Finally, because no acyclovir susceptibility testing was performed it is possible that a very rare isolate resistant to acyclovir was missed but one that was still sensitive to penciclovir as a consequence of mutant HSV polymerase. Nevertheless, results from this study are consistent with those published previously 14–18 and confirm the low incidence of antiviral resistance in this patient population.…”

Section: Discussionsupporting

confidence: 93%

“…These findings support previous observations that HSV resistance to penciclovir and other antiviral nucleoside analogues continues to be rare accounting for just 0.1–0.7% of isolates from immunocompetent patients even following prolonged therapy 14–18 . In a longitudinal susceptibility program involving 11 multinational clinical trials using chronic suppressive treatment with penciclovir or famciclovir in immunocompetent and immunocompromised patients, there was no evidence of reduced penciclovir sensitivity in viral isolates obtained during or after treatment 16 .…”

Section: Discussionsupporting

confidence: 91%

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Single-day famciclovir for the treatment of genital herpes: follow-up results of time to next recurrence and assessment of antiviral resistance

Bodsworth¹,

Fife

Koltun

et al. 2009

Current Medical Research and Opinion

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Background Episodic therapy of genital herpes is usually recommended for patients with infrequent symptomatic recurrences and where transmission is not a concern. While shorter courses are as effective as standard 5-day regimens, it is unknown whether abbreviated therapy has detrimental effects on natural history and the development of antiviral resistance. Objectives To assess time to next recurrence and development of antiviral resistance in patients with recurrent genital herpes treated with either single-day famciclovir (1 g twice-daily) or 3-day valacyclovir (500 mg twice-daily). Methods Longer-term, follow-up data on the time to next recurrence and antiviral sensitivity were collected from a previously reported multicenter, multinational, double-blind, parallel group study in which 1179 immunocompetent adults were randomized 1:1 to receive either single-day famciclovir or 3-day valacyclovir. Treatment was self-initiated within 6 hours of a recurrence. Swabs for viral culture and sensitivity testing were collected for two sequential recurrences. Results The median time to next recurrence from treatment initiation was 33.5 days for famciclovir and 38.0 days for valacyclovir. No drug resistance to penciclovir, the active metabolite of famciclovir, was observed at baseline nor did any develop by the time of the next recurrence. Limitations The study had no placebo arm, typing of viral isolates was not performed and viral resistance testing was restricted to penciclovir only. Conclusion Treatment with single-day famciclovir for recurrent genital herpes did not shorten the time to the next recurrence. Drug resistance to penciclovir continues to be a rare event in immunocompetent patients.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Single-day famciclovir for the treatment of genital herpes: follow-up results of time to next recurrence and assessment of antiviral resistance

Bodsworth¹,

Fife

Koltun

et al. 2009

Current Medical Research and Opinion

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“…Treatment resistance should be considered in patients CCrl Creatinine clearance; PE Phenytoin equivalents; SE Status epilepticus who are not responding as expected to standard treatment, or when there is evidence of clinical worsening, though it can be difficult to determine whether this represents treatment failure or the natural course of the illness. Three primary mechanisms of viral resistance to aciclovir have been described: absent or decreased levels of thymidine kinase, decreased phosphorylation of aciclovir by thymidine kinase, and decreased affinity of viral DNA polymerase for aciclovir triphosphate [114,115].…”

Section: Antiviral Medicationmentioning

confidence: 99%

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

2016

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Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be lifesaving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

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“…32 Researchers have reported acyclovir resistance in 4%-7%, in HIV positive, patients. 33 However, all our patients showed complete healing with acyclovir irrespective of HIV status. HIV co-infected patients took significantly longer to heal as given in Table 1.…”

Section: Healing With Acyclovirmentioning

confidence: 62%

Genital herpes and HIV status: a clinical study

2017

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Background: Genital herpes (GH) is a sexually transmitted infection (STI) increases risk of human immunodeficiency virus (HIV) infection. Some risk factors like age, sex, previous genital ulcerative disease (GUD), number of sex partners and clinical presentations like number and size of erosions, number of episodes, inter-episode duration, healing period with acyclovir & co-STDs are studied with reference to HIV status.Methods: This is a longitudinal, observational study comparing 25 patients each in HIV positive and negative groups of GH between 15-60 years of age in both genders. Chi square test (or Fisher’s exact test) for nominal data and ‘t’ test for continuous data was used in case of association. Mann Whitney U test was used for comparison of mean ranks and median.Results: Adolescents were 18%. HIV positivity was significantly associated with age group above 45 years, multiple sex partners, average number of episodes & the duration between them and number of erosions (p <0.05). Healing period with acyclovir in HIV positive patients was significantly longer than in HIV negative patients. Secondary syphilis a co-STD had significant association with HIV positivity. Though previous GUD alone was not associated with HIV positivity significantly; however GUD in patients with multiple sexual partners showed significant association with HIV. Conclusions: High proportion of adolescents amongst GH patients is notable. Adolescents & older patients above 45 years should not be neglected in STD & HIV awareness. Risk factors must be interviewed with patients. Clinical parameters & risk factors, differs with HIV status.

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Resistance of Herpes Simplex Virus Infections to Nucleoside Analogues in HIV‐Infected Patients

Cited by 118 publications

References 89 publications

Single-day famciclovir for the treatment of genital herpes: follow-up results of time to next recurrence and assessment of antiviral resistance

Single-day famciclovir for the treatment of genital herpes: follow-up results of time to next recurrence and assessment of antiviral resistance

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

Genital herpes and HIV status: a clinical study

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