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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.
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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 ,
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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