Clinical and virologic characterization of acyclovir-resistant varicella-zoster viruses isolated from 11 patients with acquired immunodeficiency syndrome.

We studied the clinical resistance to acyclovir of infections with varicella-zoster viruses (VZV) in patients with acquired immunodeficiency syndrome, and we correlated it to virologic analyses. Eleven patients with VZV infections (treated with acyclovir, 30 mg/kg/day, given intravenously, or 4 g/day, given orally) were included in the study because of the failure of 10 days of acyclovir therapy. Susceptibility of VZV isolates to acyclovir was tested using a plaque reduction assay to determine the 50% inhibitory concentration (IC(50)) of acyclovir and the SI(50) (IC(50) of the patient isolate/IC(50) of the reference strain) to acyclovir. The thymidine kinase (TK) gene, which supports the resistance, was sequenced on amplified products. Only 3 patients had a significant increase in the IC(50), as compared with the IC(50) of the reference strain (SI(50) of > or =4), and a mutation in the TK gene. For the other 8 patients, the clinical resistance was not confirmed by the virologic results: the SI(50) was < 4, and no mutation was detected in the TK gene. Because no acyclovir-resistant strain appeared during a shorter period of time, we suggest an increase in the duration of the treatment to 21 days before acyclovir resistance is suspected.

[Efficacy of cidofovir in an HIV infected patient with an acyclovir and foscarnet resistant herpes simplex virus infection]. / Efficacité du cidofovir dans un herpès cutané résistant à l'aciclovir et au foscarnet chez un malade séropositif pour le VIH.

BACKGROUND: We report the case of an AIDS patient, whose persistant HSV2 ulceration was clinically and phenotypically resistant to acyclovir and foscarnet. Only five clinical isolates of simultaneous acyclovir and foscarnet resistance have been previously described. CASE REPORT: This patient, without history of opportunistic infection, was hospitalized for a recurrent scrotal ulceration resistant to several antiviral treatment such as acyclovir, valacyclovir or foscarnet. The CD4 count was stable at 150/mm(3) and the HIV viral load was below detection level. The last recurrence appeared rapidly under valacyclovir therapy which had been introduced after 65 days of foscarnet therapy. Thus, the patient received a new dose of foscarnet. After initial efficacy, the ulceration increased once again. HSV2 phenotypic determination was done and detected, at that time, a double resistance to acyclovir and foscarnet. Healing was obtained with intravenous cidofovir. DISCUSSION: Foscarnet and acyclovir resistance in an HSV2 isolate is rare. This report presents several particularities. First, whereas the earlier published patients with an acyclovir and foscarnet resistant strain were widely immunocompromised, this was not the case for our patient. Secondly, in contrast with most precedent observations in which acyclovir-resistant strain disappeared after foscarnet therapy, in our case the acyclovir resistant strain remained after foscarnet therapy. Finally, few reports concerned the clinical efficacy of cidofovir in HSV infection. In this case, we proved that intravenously cidofovir was highly and rapidly effective on acyclovir and foscarnet resistant strains.

[Varicella-zoster virus]. / Virus varicelle-zona.

Varicella-zoster virus, an ubiquitous human pathogen, causes vesicular rash during varicella, the primary infection of the host and zoster corresponding to reactivation. The symptoms could be various, nervous systems and lung being involved. Usually mild, varicella could be severe in immunocompromised patients, during pregnancy for the mother and the foetus, for the newborn and also for adults. Post herpetic neuralgia in old patient is the main complication of zoster. Various methods for virological diagnosis (culture, cytology, serology, PCR) with different sensibilities and specificities depending mainly of sample type are available. Various antiviral drugs are available, acyclovir being the reference one.

Paraneoplastic pemphigus with circulating antibodies directed exclusively against the pemphigus vulgaris antigen desmoglein 3.

A patient with follicular B-cell lymphoma presented with erythroderma associated with cutaneous and mucosal blisters. Histologic and direct immunofluorescence analysis of lesional skin showed a typical pattern of paraneoplastic pemphigus (PNP). Interestingly, indirect immunofluorescence on rat bladder was negative and immunoblot analysis of the patient's serum on epidermal extracts demonstrated antiepidermal antibodies that only recognized the pemphigus vulgaris antigen desmoglein 3, with no antibodies directed against the different proteins of the plakin family. To our knowledge this has never been reported in the literature. It exemplifies the overlap between pemphigus vulgaris and PNP and the pathogenic role of anti-desmoglein 3 antibodies in PNP. Moreover, it underscores the need to consider clinical, histologic, and immunologic features for the diagnosis of PNP.