Recalcitrant Pseudotumoral Anogenital Herpes Simplex Virus Type 2 in HIV-Infected Patients: Evidence for Predominant B-Lymphoplasmocytic Infiltration and Immunomodulators as Effective Therapeutic Strategy

Sbidian, É.; Battistella, Maxime; Goff, Jérôme Le; Lafaurie, Matthieu; Bézier, M.; Agbalika, F.; Simon, François; Bouscarat, F.; Cayuela, Jean‐Michel; Carcelain, Guislaine; Houhou, Nadira; Bagot, Martine; Molina, Jean Michel; Janier, M.; Bachelez, Hervé

doi:10.1093/cid/cit592

Cited by 54 publications

(69 citation statements)

References 38 publications

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“…In addition, viral resistance to nucleos(t)ide analog drugs has been observed in immunocompromised adults (17)(18)(19)(20)(21)(22), pediatric patients (23), and immunocompetent persons with herpetic stromal keratitis or uveitis (24)(25)(26). The emergence of drug-resistant and multidrug-resistant viruses has been linked to severe complications in immunocompromised individuals (27)(28)(29)(30). More effective suppression of HSV will require new drugs that will likely be used in combination with nucleos(t)ide analogs.…”

mentioning

confidence: 99%

Synthetic α-Hydroxytropolones Inhibit Replication of Wild-Type and Acyclovir-Resistant Herpes Simplex Viruses

Ireland

Tavis

D’Erasmo

et al. 2016

Antimicrob Agents Chemother

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cHerpes simplex virus 1 (HSV-1) and HSV-2 remain major human pathogens despite the development of anti-HSV therapeutics as some of the first antiviral drugs. Current therapies are incompletely effective and frequently drive the evolution of drug-resistant mutants. We recently determined that certain natural troponoid compounds such as ␤-thujaplicinol readily suppress HSV-1 and HSV-2 replication. Here, we screened 26 synthetic ␣-hydroxytropolones with the goals of determining a preliminary structure-activity relationship for the ␣-hydroxytropolone pharmacophore and providing a starting point for future optimization studies. Twenty-five compounds inhibited HSV-1 and HSV-2 replication at 50 M, and 10 compounds inhibited HSV-1 and HSV-2 at 5 M, with similar inhibition patterns and potencies against both viruses being observed. The two most powerful inhibitors shared a common biphenyl side chain, were capable of inhibiting HSV-1 and HSV-2 with a 50% effective concentration (EC 50 ) of 81 to 210 nM, and also strongly inhibited acyclovir-resistant mutants. Moderate to low cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC 50 ] of 50 to >100 M). Therapeutic indexes ranged from >170 to >1,200. These data indicate that troponoids and specifically ␣-hydroxytropolones are a promising lead scaffold for development as anti-HSV drugs provided that toxicity can be further minimized. Troponoid drugs are envisioned to be employed alone or in combination with existing nucleos(t)ide analogs to suppress HSV replication far enough to prevent viral shedding and to limit the development of or treat nucleos(t)ide analog-resistant mutants.

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mentioning

confidence: 99%

Synthetic α-Hydroxytropolones Inhibit Replication of Wild-Type and Acyclovir-Resistant Herpes Simplex Viruses

Ireland

Tavis

D’Erasmo

et al. 2016

Antimicrob Agents Chemother

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“…2017;6(2-3):68-71 or tumoral hypertrophic lesions as seen in HSV-2 infection in immunocompromised patients. Occasional cases of HSV-2 infection in HIV-infected patients have been reported in whom HSV-2 causes formation of mass or tumoral lesions in the anogenital regions [5,7,8]. While similar HSV-2 infection in the genital region has been reported in patients with other immunocompromised conditions such as common variable immunodeficiency and organ transplant recipients, such reports are extremely rare [6,9].…”

Section: Discussionmentioning

confidence: 99%

“…Reactivation of HSV-1 occurs with various trigger factors and usually forms red macules on the mucocutaneous junction of the lips which rapidly become vesicular, then form pustular scabs and ulcers. HSV-1 may form atypical lesions in immunocompromised patients; however, it is extremely rare that it forms mass, tumoral, or hypertrophic lesions as occasionally seen in the anogenital regions of patients infected with human immunodeficiency virus (HIV) due to HSV type 2 (HSV-2) infection [2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Hypertrophic Herpes Simplex Virus Type 1 Infection in a Patient With Acute Myeloid Leukemia

et al. 2017

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A 64-year-old woman had a transformation from polycythemia vera to acute myeloid leukemia. While she was treated with azacitidine and prednisolone, a nodule at the left angle of the mouth developed, which was biopsied and diagnosed with hypertrophic herpes simplex virus type 1 (HSV-1) infection. The nodule resolved completely with aciclovir. While HSV type 2 virus occasionally forms mass or tumoral lesions in immunocompromised, especially acquired immunodeficiency syndrome, patients, it is extremely rare that HSV-1 infection leads to similar lesions. The hematological conditions and the therapies given may have contributed to the rare manifestation of HSV-1 infection.

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“…However, HSV infection can also present as hypertrophic or tumorous lesions [3, 5, 8–10]. The largest series has been published by Sbidian and coworkers, who described the clinical characteristics of ten HIV-infected patients with pseudotumors associated with HSV-2.…”

Section: Discussionmentioning

confidence: 99%

“…No coinfection with HSV-1 was observed in this series. Histopathologic exam of the lesions in each case showed a moderately dense dermal polytypic plasma cell infiltrate [3]. …”

Section: Discussionmentioning

confidence: 99%

Leflunomide in the Treatment of a Pseudotumoral Genital Herpes Simplex Virus Infection in an HIV Patient

Roger¹,

Anstead

2017

Case Reports in Infectious Diseases

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The patient is a 52-year-old African American man with a past medical history of HIV infection (on antiretroviral therapy, CD4 count 399 cells/µL, and undetectable HIV viral load) and recurrent genital herpes. While on valacyclovir, the patient presented with four tumorous lesions on the perineum and scrotum. A biopsy specimen stained positively with HSV-1 and HSV-2 immunostains and displayed a lymphoplasmacytic infiltrate. The patient received foscarnet and imiquimod for two weeks with minimal improvement. Based on the previous activity of leflunomide, which has both antiviral and immunomodulatory properties, in cytomegalovirus and herpes simplex infections, leflunomide 20 mg orally twice daily was started. The patient received 23 days of foscarnet, 14 days of topical imiquimod, and 11 days of leflunomide with approximately 80% reduction in the size of the perineal lesion. After nine months on leflunomide there was complete regression of the large perineal lesion and only two small ulcerations remained on the scrotum. Pseudotumoral herpes lesions in HIV patients represent an immune reconstitution event and are poorly responsive to the usual anti-herpes agents. This report demonstrates the successful use of leflunomide in the treatment of an HIV patient with pseudotumoral herpes. Thalidomide has also been used with some success.

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Recalcitrant Pseudotumoral Anogenital Herpes Simplex Virus Type 2 in HIV-Infected Patients: Evidence for Predominant B-Lymphoplasmocytic Infiltration and Immunomodulators as Effective Therapeutic Strategy

Cited by 54 publications

References 38 publications

Synthetic α-Hydroxytropolones Inhibit Replication of Wild-Type and Acyclovir-Resistant Herpes Simplex Viruses

Synthetic α-Hydroxytropolones Inhibit Replication of Wild-Type and Acyclovir-Resistant Herpes Simplex Viruses

Hypertrophic Herpes Simplex Virus Type 1 Infection in a Patient With Acute Myeloid Leukemia

Leflunomide in the Treatment of a Pseudotumoral Genital Herpes Simplex Virus Infection in an HIV Patient

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