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Journal of Antimicrobial Chemotherapy Advance Access published September 23, 2010
or possible neoplasm, and extensive workup showed no evidence of vascular abnormality or CNS vasculitis. The patient had no riskfactors for HIV infection and past medical history was unremark- able. The patient was transferred to our institution for further Upon admission, the patient presented with slurred speech, dif- ficulty verbalizing their thoughts and right-sided weakness.
Laboratory results included a normal white blood cell count, Amila Patel1*, Julie Patel2 and Judy Ikwuagwu1 with normal neutrophil and slightly depressed lymphocytecounts. MRI revealed multiple white matter lesions throughout the brain, consistent with a demyelinating process. A brain The Methodist Hospital, 6565 Fannin Street, DB1-09, Houston, biopsy confirmed characteristic findings of PML, with enlarged TX 77030, USA; 2The Methodist Hospital, 6550 Fannin Street, oligodendroglial nuclei and intranuclear ground glass-type Suite 1115, Smith Tower, Houston, TX 77030, USA inclusions. In situ hybridization for JC viral genome sequences *Corresponding author. Tel: +1-813-745-6373; was positive and the JC viral load was reported as 3600 copies/mL.
Because of the PML diagnosis, HIV screening, T cell subset cell count and immunoglobulin tests were carried out. Serological Keywords: JC virus, immunodeficiency, cidofovir tests by ELISA and PCR analysis were negative for HIV-1, HIV-2and human T-lymphotropic virus-1 and -2, and immunoglobulin studies were normal (IgG total 974 mg/dL, IgG1 501 mg/dL, We present the case of a patient with progressive multifocal leu- IgG2 217 mg/dL, IgG3 64 mg/dL, IgG4 4 mg/dL, IgA 350 mg/dL koencephalopathy (PML), caused by the human polyoma virus and IgM 210 mg/dL). Initial T cell counts were markedly decreased JC, who was found to have a CD4+ count of 87 cells/mm3 and at 87 and 111 cells/mm3. Based upon these results, a diagnosis was subsequently diagnosed with idiopathic CD4+ lymphocyto- of PML with ICL was made and the challenge of creating an appro- penia (ICL). To our knowledge, this is the first reported case on the use of multiple agents targeted against both PML and ICL.
After a discussion of potential options and a review of pub- A patient presented at an outside hospital with progressive lished literature, as described in the accompanying review right-sided weakness, numbness, mouth droop and speech article,therapy was initiated with three main goals: (i) to loss. At that time, the patient was diagnosed with an ischaemic decrease JC virus levels; (ii) to increase CD4+ cell counts; and cerebrovascular accident and was started on appropriate (iii) to prevent other opportunistic infections. Because the avail- therapy. Despite physical therapy, the patient continued to able options for the treatment of PML are limited and published deteriorate and was re-evaluated after 2 months. Magnetic res- data are based on case reports, it was decided to provide a com- onance imaging (MRI) at that time revealed progression of stroke bination of agents shown to be active against JC virus. The 14/1 21/1 28/1 4/2 11/2 18/2 25/2 4/3 11/3 18/3 25/3 1/4 Figure 1. Patient trend in viral load and CD4+ count. *Assay unable to detect viral load below a lower limit of 100 DNA copies/mL.
# The Author 2010. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
For Permissions, please e-mail: [email protected] patient was started on cidofovir [5 mg/kg intravenous (iv) CMX001 treatment, neurological function stabilized and the ×2 weeks], risperidone (2 mg orally every 12 h) and mefloquine patient has not had any further decline since that time.
(250 mg orally ×3 days, then weekly). An investigational oral A recent swallowing study showed improvement and our agent for the treatment of PML, CMX001, was given to the patient is now tolerating a pureed diet.
patient after the initial 2 weeks of iv cidofovir. The patient also This was the first case report to demonstrate the use of mul- received an investigational interleukin-7 (CYT107) to increase tiple agents, including investigational medications, as a possible their CD4+ cell counts. Initiation of this therapy was delayed therapeutic strategy in the treatment of PML with ICL. The until viral loads decreased, in order to avoid immune reconstitu- patient’s clinical symptoms are slowly improving and the tion syndrome. Finally, the patient was given appropriate prophy- reduction in viral load over 8 weeks of therapy is promising, but laxis with dapsone (100 mg orally daily), according to CDC long-term evaluation will be necessary. In addition, further con- recommendations for a CD4+ count of ,200 cells/mm3.
trolled studies are important to determine whether these Four weeks after the initiation of therapy for JC virus with ris- approaches are effective against the two rare and debilitating peridone, iv cidofovir and mefloquine, the patient’s serum viral load was 3456 copies/mL. The patient’s neurological functionwas declining, as their left hand started becoming weaker andthey had difficulty swallowing and speaking. Repeat MRI showed a new area of dysfunction in the right portion of the brain that correlated with weakness in the left hand and persist-ent presence of demyelination in multiple areas of the brain. It isimportant to note that, at this point, iv cidofovir was discontin-ued after two doses. In addition, we noticed a drop in the patient’s haemoglobin and, with a suspicion for haemolytic anaemia, both mefloquine and dapsone were discontinued.
CMX001 was then initiated and, 1 week later, the serum viralload had decreased to 1700 copies/mL. Subsequent values were 800, 100 and 100 copies/mL at 3, 5 and 7 weeks 1 Patel A, Patel J, Ikwuagwu J. Treatment of progressive multifocal after CMX001 initiation, respectively. Changes in CD4+ counts and viral loads over time are shown in Figure By day 7 of J Antimicrob Chemother 2010; in press.

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