No abstract

Experimental evidence and pathological observation indicate that human cytomegalovirus (HCMV) has a tropism for cells of the nervous system, including both neuronal and glial cells. As demonstrated in animal models, after a viremic phase, the virus may reach the brain, where it may cause mild infection or severe encephalitis. The nervous system is one of the principal target organs in congenital HCMV infections and in HCMV-infected AIDS patients. In the former case, mortality is high and neurological sequelae, such as mental retardation, are frequent; in the latter it may lead to a progressively wasting encephalopathy and death within a few weeks. The diagnosis of the nervous system manifestations due to HCMV can now rely upon the detection of HCMV DNA in cerebrospinal fluid by means of polymerase chain reaction. However, the current antiviral treatments of these complications are of limited effect.

SUMMARYPlasma levels of soluble CD27 (sCD27) are elevated in diseases characterized by T cell activation and are used as a marker of immune activation. We assessed the usefulness of determining plasma sCD27 as a marker for monitoring immune activation in HIV-1-infected patients treated with highly active antiretroviral therapy (HAART). A first cross-sectional examination of 68 HIV-1-infected and 18 normal subjects showed high levels of sCD27 in HIV-1 infection; plasma sCD27 was correlated to HIV-1 viraemia and inversely correlated to CD4 + T cell count. Twenty-six HIV-1-infected patients undergoing HAART were studied at baseline and after 6, 12, 18 and 24 months of therapy. Seven additional patients under HAART were analysed at baseline, during and after interruption of therapy. In the total population, HAART induced a significant and progressive reduction, but not a normalization, of plasma levels of sCD27 after 24 months. A full normalization of plasma sCD27 was observed in the virological responders (undetectable HIV-1 RNA at months 18 and 24) and also in patients with moderate immunodeficiency at baseline (CD4 + T cell count >200 cells/mm 3 ). Changes in plasma neopterin paralleled the changes in sCD27 but only baseline sCD27 levels were predictive of a greater increase in CD4 + T cell count during the follow-up. Discontinuation of therapy resulted in a rapid increase of sCD27 plasma levels associated with viraemia rebound and drop in CD4 + T cell count. Our findings suggest that plasma sCD27 may represent an alternative and simple marker to monitor immune activation during potent antiretroviral therapy. HIV-1-induced immune activation can be normalized by HAART in successfully treated patients where the disease is not advanced.

A duplex polymerase chain reaction (PCR) assay for DNA from herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) was applied to cerebrospinal fluid (CSF) from 918 human immunodeficiency virus (HIV) -infected patients with neurological symptoms. HSV-1 or HSV-2 (HSV-1/2) DNA was found in 19 patients (2%). For the 258 patients for whom a diagnosis was confirmed at autopsy, the sensitivity and specificity of PCR analysis for the diagnosis of HSV-1/2 encephalitis were 100% and 99.6%, respectively. Three patients with CD4/ cell counts of §170/mL had HSV-1 central nervous system (CNS) infections (two) or HSV-2 meningitis (one). Sixteen patients with CD4/ cell counts of õ40/mL had HSV-1 CNS infections (two) or mixed HSV-1/2 and cytomegalovirus encephalitis (14). The response to antiviral treatment, which was assessed clinically and by CSF PCR analysis, was variable in the patients with the highest CD4/ cell counts and poor in those with more severe immunosuppression. CSF PCR analysis is of value for the diagnosis and follow-up of treatment of HSV-1/2 CNS infections in HIV-infected patients.Herpes simplex virus (HSV) encephalitis is one of the most diagnosed in vivo by means of brain biopsy [19, 20], virus isolation from CSF [20, 21], or, in a single case, by PCR common encephalitides occurring in immunocompetent patients [1]. It is usually caused by HSV type 1 (HSV-1), and analysis of CSF [22]. In the present study, a duplex PCR assay for DNA from its diagnosis primarily relies on the detection of viral DNA in CSF by means of PCR analysis [2 -4]. Several studies have HSV-1 and HSV-2 was applied to CSF samples taken from a large series of HIV-infected patients with neurological sympdemonstrated that this procedure is highly reliable, rapid, and minimally invasive in comparison with brain biopsy, which has toms to identify HSV-1/2 CNS infections. Various aspects of these infections were examined, including the following: the for years been considered the gold standard for the diagnosis of herpes encephalitis. Furthermore, because of the excellent prevalence of HSV-1/2 genomes in CSF; the diagnostic potential of CSF PCR analysis by comparing results of CSF PCR sensitivity of PCR analysis, a spectrum of clinical syndromes caused by infection of the nervous system due to either HSVanalysis with neuropathological findings; the clinical modalities of presentation; the effects of antiviral treatments on virological 1 or HSV type 2 (HSV-2) has been identified, including forms with an atypical course or unusual localization [4,5].and clinical parameters; the presence of HSV-1/2 genomes in blood; and the presence of an intrathecal immune response to A number of cases of HSV-1 or HSV-2 (HSV-1/2) CNS infections have also been described in HIV-infected individuals the infection. [6 -22]. These cases were characterized by the atypical topography and histology of the lesions, and most of them werePatients and Methods associated with cytomegalovirus (CMV) encephalitis [6, 8 -12, 15 -18, 22]. Most of the reported cases were identified Pati...

The objective was to evaluate the frequency of human herpesvirus 6 (HHV-6) DNA detection in the CSF of patients infected with HIV and its relation to brain disease and systemic HHV-6 infection.Nested polymerase chain reaction (PCR) was used to analyse CSF samples from 365 consecutive HIV infected patients with neurological symptoms. When available, plasma and brain tissues from patients whose CSF was HHV-6 positive were also studied.HHV-6 was found in the CSF of eight of the 365 patients (2.2%): two had type A and four type B; the HHV-6 variant could not be defined in the remaining two. All eight patients had neurological symptoms and signs related to concomitant opportunistic brain diseases, including cytomegalovirus (CMV) encephalitis in five patients whose CSF was also positive for CMV-DNA. Opportunistic infections but no other unexplained lesions were also found in the brain of all of the four patients who underwent neuropathological examination. Both HHV-6 and CMV were also detected in the plasma of respectively five and seven of seven patients whose CSF was HHV-6 positive.In conclusion, HHV-6 type A or B DNA was infrequently found in the CSF of HIV infected patients, in association with both CMV brain infection and systemic HHV-6 replication. However, no certain relation between HHV-6 and brain disease was found. (J Neurol Neurosurg Psychiatry 1999;67:789-792)