Foscarnet-resistant Herpes Simplex Research Articles

Successful treatment of aciclovir and foscarnet resistant Herpes simplex virus lesions with topical imiquimod in patients infected with human immunodeficiency virus type 1

Aciclovir (ACV)-resistant Herpes simplex virus type-2 (HSV-2) infections are observed commonly in patients also infected with HIV-1. The use of foscarnet (FOS) in these patients may also lead to resistance. This situation can become a difficult therapeutic challenge. Four cases of patients infected with HIV and with mucocutaneous HSV-2 resistant to ACV and FOS are reported. These patients were treated successfully with topical 5% imiquimod. Imiquimod treatment also appeared to delay the time to recurrence of HSV lesions.

Oral topical cidofovir: novel route of drug delivery in a severely immunosuppressed patient with refractory multidrug‐resistant herpes simplex virus infection

We present a case of serious treatment-refractory acyclovir- and foscarnet-resistant herpes simplex virus (HSV) type-1 orolingual infection that responded to oral cidofovir rinses after failure of acyclovir and foscarnet therapy. The use of 3% cidofovir in a saline rinse for refractory mucosal HSV infection appears promising but needs prospective evaluation.

Genotypic Characterization of the DNA Polymerase and Sensitivity to Antiviral Compounds of Foscarnet-Resistant Herpes Simplex Virus Type 1 (HSV-1) Derived from a Foscarnet-Sensitive HSV-1 Strain

Foscarnet is widely used for the treatment of acyclovir-resistant herpesvirus infections, and foscarnet-resistant herpesvirus infections are a serious concern in immunocompromised patients. Twenty-seven single-plaque isolates of herpes simplex virus type 1 (HSV-1) resistant to foscarnet were selected from foscarnet- and acyclovir-sensitive HSV-1 strain TAS by exposure to foscarnet, and the DNA polymerase genes were analyzed. The sensitivities of these mutants to foscarnet, cidofovir, S2242, acyclovir, ganciclovir, and penciclovir were determined. A single amino acid substitution, double amino acid substitutions, and a combination of a single amino acid substitution with a deletion or insertion of amino acid residues in the viral DNA polymerase were demonstrated in 21, 4, and 2 isolates, respectively. Of the 27 isolates, an amino acid substitution of serine for asparagine at amino acid position 724 in the DNA polymerase (724 S-N) was detected in 8 isolates. An amino acid substitution in conserved region II was demonstrated in these eight isolates as well as four other isolates. The mutation in the DNA polymerase responsible for resistance to foscarnet was located between the pre-IV region and conserved region V, especially within conserved region II. All the isolates were sensitive or hypersensitive to cidofovir and ganciclovir. Seven, 5, and 15 of the 27 isolates were also sensitive to S2242, acyclovir, and penciclovir, respectively. Thus, most of the foscarnet-resistant HSV-1 isolates were sensitive or hypersensitive to cidofovir and ganciclovir.

Novel mutations in the thymidine kinase and DNA polymerase genes of acyclovir and foscarnet resistant herpes simplex viruses infecting an immunocompromised patient.

Mutations in the thymidine kinase (TK) and DNA polymerase (pol) genes of herpes simplex virus (HSV) may confer resistance to antiviral drugs, particularly in the context of immunosuppression induced by infection with the human immunodeficiency virus (HIV). To characterise the HSV type 2 (HSV-2) TK and DNA pol genes in an immunocompromised patient with clinical resistance to both acyclovir and foscarnet. The TK and DNA pol genes of isolates obtained over a 2-year period from an AIDS patient with severe genital herpes infection were characterised both phenotypically and genotypically. HSV strains that were acyclovir resistant/foscarnet sensitive, acyclovir sensitive/foscarnet sensitive and acyclovir resistant/foscarnet resistant were isolated during this time. The TK gene of all the acyclovir resistant isolates contained a large 969 bp deletion which extended into a downstream untranslated region. The foscarnet resistance was associated with an S725G mutation in a conserved region (region II) of the herpesvirus DNA pol gene. Clinical and virological suppression of the infection was not always associated with subsequent reactivation with wild-type virus. Mutations of the nature we describe have not previously been reported occurring simultaneously in HSV strains isolated from patients treated with acyclovir and foscarnet.

Development of drug-resistant herpes simplex virus infection after haploidentical hematopoietic progenitor cell transplantation

AbstractAn unusually high incidence of acyclovir- and foscarnet-resistant herpes simplex virus (HSV) infection was noted after lymphocyte-depleted blood hematopoietic progenitor cell (HPC) transplantation from HLA-haploidentical family donors. Fourteen adults with hematologic malignancies underwent blood HPC transplantation from haploidentical family donors. Pheresis products were stringently depleted of T and B cells by immunomagnetic adsorption, and patients received no immunosuppression after transplantation. HSV reactivation occurred in all 7 evaluable HSV-1– or HSV-2–seropositive patients, at a median of 40 days after transplantation. Susceptibility testing of clinically resistant viral isolates demonstrated acyclovir resistance in all 5 cases tested. Second-line therapy produced only partial responses, and in vitro evidence of foscarnet resistance developed rapidly in all 3 patients treated with foscarnet. Healing of lesions coincided with T-cell recovery. The prolonged immunodeficiency associated with stringent lymphocyte depletion of the graft appears to strongly predispose to emergence of drug-resistant HSV. Furthermore, immune reconstitution is necessary for eradication of infection.

Treatment of an acyclovir and foscarnet-resistant herpes simplex virus infection with cidofovir in a child after an unrelated bone marrow transplant

Herpes simplex virus (HSV) causes serious problems in immuno-compromised patients such as those receiving a bone marrow transplant (BMT) for a hematological malignancy. Resistance to acyclovir (ACV) is a growing major concern. Foscarnet is a non-thymidine kinase-dependent agent, but the emergence of ACV and foscarnet-resistant HSV requires a new therapeutic approach. We describe a girl treated with cidofovir for a life-threatening ACV-resistant HSV infection after an unrelated BMT for a relapse of an acute myeloblastic leukemia (AML).

The in vitro activity of cidofovir against acyclovir-resistant and foscarnet-resistant herpes simplex virus (HSV) isolates : S. Safrin, E. Abarbarchuk, E. Palacios. The Herpes Virus Research Laboratory, San Francisco General Hospital, San Francisco CA

The in vitro activity of cidofovir against acyclovir-resistant and foscarnet-resistant herpes simplex virus (HSV) isolates : S. Safrin, E. Abarbarchuk, E. Palacios. The Herpes Virus Research Laboratory, San Francisco General Hospital, San Francisco CA

136 Evaluation of the in vitro activity of SP-303 against clinical isolates of acyclovir-resistant and foscarnet-resistant herpes simplex virus (HSV) : S. Safrin, L. Phan, T. Elbeik. University of California, San Francisco CA

136 Evaluation of the in vitro activity of SP-303 against clinical isolates of acyclovir-resistant and foscarnet-resistant herpes simplex virus (HSV) : S. Safrin, L. Phan, T. Elbeik. University of California, San Francisco CA

20 Foscarnet-resistant herpes simplex virus (HSV) infections in patients with AIDS: S. Safrin, S. Kemmerly, B. Plotkin, T. Smith, N. Weissbach, D. De Veranez, L. Phan, D. Cohn. University of California, San Francisco CA; Ochsner Medical Institution, New Orleans LA; Minor & James Medical Center, Seattle WA; University of Washington, Seattle WA; St. Vincent's Health Center, Erie PA; Sutphin Medical

20 Foscarnet-resistant herpes simplex virus (HSV) infections in patients with AIDS: S. Safrin, S. Kemmerly, B. Plotkin, T. Smith, N. Weissbach, D. De Veranez, L. Phan, D. Cohn. University of California, San Francisco CA; Ochsner Medical Institution, New Orleans LA; Minor & James Medical Center, Seattle WA; University of Washington, Seattle WA; St. Vincent's Health Center, Erie PA; Sutphin Medical