Scand J Infect Dis 33: 398–399, 2001 LETTER TO THE EDITOR
Varicella-zoster Virus Meningitis andCerebrospinal Fluid HIV RNAOSWALD MOLING1, PATRIZIA ROSSI2, GIOVANNI RIMENTI1,CLAUDIO VEDOVELLI1 and PETER MIAN1
From the 1Di×ision of Infectious Diseases and 2Laboratory of Microbiology, Ospedale Generale, Bolzano, Italy
Sir,We read with interest the report by De La Blanchardiere et al.
(1), who described a large number of cases of neurological compli-cations of varicella-zoster virus (VZV) infection in adults with HIVinfection before the highly active antiretroviral therapy period.Neurological complications of VZV infection occurred in the ab-sence of rash in 29% of these cases. In such circumstances thediagnosis is dif� cult, but detection of VZV DNA in the cere-brospinal � uid (CSF) using the PCR technique allows con� rmationof a suspected diagnosis. Neurological complications of VZVinfection are reported to be more severe and more frequent inimmunocompromised adult patients, including those with HIVinfection. Conversely, does VZV infection of the central nervoussystem (CNS) promote HIV meningitis or HIV infection of thebrain?
We treated a 36-y-old previously asymptomatic HIV-infectedand antiretrovirally naive patient with VZV meningitis and tho-racic herpes zoster with acyclovir 30 mg:kg for 2 weeks. All themajor symptoms, including fever, headache and neck stiffness,disappeared within a few days but, during the course of thedisease, a rise in the HIV RNA level in the CSF from 1500 to20,000 copies:ml was observed (see Table I). HIV copy numberswere determined using a commercially available quantitative PCRassay (Amplicor HIV Monitor, Roche Diagnostic Systems). A CSFcontrol examination of the asymptomatic patient 2 weeks laterrevealed a further rise in HIV RNA to 49,800 copies:ml. At thistime antiretroviral therapy with zidovudine, lamivudine and nevi-rapine was started.
Just as immune activation due to immunization or infection cantemporarily increase HIV viremia, so the VZV infection of themeninges might have stimulated the HIV replication in the CSF of
the patient. This might have been mediated locally by pro-in� am-matory cytokines and by activation of CD4 T lymphocytes, whichis required for HIV to replicate. In addition, the in� ammatorymeningeal process might have increased traf� cking of monocytesand T lymphocytes into the CSF. Experiments have shown thatseveral herpes viruses can activate HIV gene expression in vitro,and this was proposed to play a role in vivo (2). There is stilldebate as to whether systemic non-CNS or CNS tissues can beconsidered the predominant source of HIV particles present in theCSF during the different stages of HIV infection (3). In the presentcase the stable plasma HIV RNA levels, compared to the higherand increasing CSF HIV RNA levels, indicate that HIV replicationwas restricted to the CNS.
High levels of HIV RNA in the CSF have been shown tocorrelate with neurologic symptoms in primary (4) and advancedHIV infection (5, 6). In 1 report high CSF HIV RNA concentra-tions (cut-off value 3 log10) correlated well with AIDS dementiacomplex severity, but CSF HIV RNA was also increased incryptococcal meningitis (5). In contrast, in the histopathologicalanalysis of Cinque et al. (6), high CSF HIV RNA levels (cut-offvalue 4.5 log10) were associated with HIV encephalitis regardless ofthe presence of opportunistic brain diseases. In addition, patientswith neurologic manifestations of primary HIV infection werereported to have an increased risk of disease progression (4).Because of these � ndings the rise in CSF HIV RNA to 49,800copies:ml observed in our patient was considered suf� cient indica-tion to start antiretroviral treatment, despite the low plasma HIVRNA level of 2860 copies:ml and the CD4 T-cell count of 351:mm3.
This case stimulates several questions. In the absence of overtneurological symptoms do high CSF HIV RNA levels predict
Table I. Laboratory � ndings in CSF and blood
Days after admission
0 7 11 28
Cerebrospinal � uidWhite cells (½106:l) 200 a 320 a 152 a 146 b
1.572.96Total protein (g:l) 1.533.95113Chloride (mmol:l) 118 119 121
VZV DNA Positive Negative NegativeHIV RNA (copies:ml) 1,500 2,500 20,000 49,800
BloodCD4 (T cells:mm3) 390 351
2,860HIV RNA (copies:ml) 2,600
a Predominantly polymorphonuclear granulocytes.b Predominantly lymphocytes.
© 2001 Taylor & Francis. ISSN 0036-5548
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Scand J Infect Dis 33 VZV meningitis in HIV infection 399
brain disease and justify preventive antiretroviral treatment?Should high CSF viral load, when combined with low plasma viralload, prompt further CSF investigations, e.g. search for immuneactivation parameters or nerve and glial cell marker proteins? Dominor neurological symptoms, e.g. slowed reaction time, reducedmemory or concentration capacity and a depressive state, in long-term non-progressors or other patients with low plasma viral loadwarrant a CSF examination?
REFERENCES
1. De La Blanchardiere A, Rozenberg F, Caumes E, Picard O,Lionnet F, Livartowski J, et al. Neurological complications ofvaricella-zoster virus infection in adults with human immuno-de� ciency virus infection. Scand J Infect Dis 2000; 32: 263–9.
2. Grif� ths PD. Herpesviruses and AIDS. Scand J Infect Dis Suppl1996; 100: 3–7.
3. Major EO, Rausch D, Marra C, Clifford D. HIV-associateddementia. Science 2000; 288: 440–2.
4. Tambussi G, Gori A, Capiluppi B, Balotta C, Papagno L,Morandini B, et al. Neurological symptoms during primaryhuman immunode� ciency virus (HIV) infection correlate withhigh levels of HIV RNA in cerebrospinal � uid. Clin Infect Dis2000; 30: 962–5.
5. Brew BJ, Pemberton L, Cunningham P, Law MG. Levels ofhuman immunode� ciency virus type 1 RNA in cerebrospinal� uid correlate with AIDS dementia stage. J Infect Dis 1997; 175:963–6.
6. Cinque P, Vago L, Ceresa D, Mainini F, Terreni MR, VaganiA, et al. Cerebrospinal � uid HIV-1 RNA levels: correlation withHIV encephalitis. AIDS 1998; 12: 389–94.
O. Moling, MD, DiØision of Infectious Diseases, Ospedale GeneraleVia Lorenz Bohler 5, IT-39100 Bolzano, Italy. E-mail: [email protected]
Submitted August 28, 2000; accepted December 6, 2000
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