Rocha, Cristiane M MD*†; Machado, Daisy M MD†; Sucupira, Maria Cecilia MD†; Succi, Regina C MD†
*Casa de Saude Santa Marcelina São Paulo, Brazil; †Universidade Federal de São Paulo São Paulo, Brazil
To the Editor:
The aim of the present study was to analyze the HIV-1 viral load in cerebrospinal fluid (CSF) of infected children with and without neurologic symptoms and to establish its relation to HIV-1 plasma viral load and antiretroviral therapy.
This study was approved by the Universidade Federal de São Paulo (UNIFESP) Ethics Committee. The cohort was divided into 2 groups: group 1 comprising antiretroviral-naive patients (10 patients) and group 2 comprising patients on antiretroviral therapy (9 patients). All consecutive HIV-1-infected patients underwent lumbar puncture after receiving local anesthesia with lidocaine 2.5%/prilocaine 2.5% topical cream and provided blood samples during 2003. A longitudinal study was performed on patients, and a second sample of blood and CSF was taken after 4 weeks or more (Table 1). In group 1, patients were prescribed therapy within 24 hours of the first lumbar puncture procedure. Five patients did not undergo a second lumbar puncture procedure, because their parents had decided against it. For virologic investigation, the blood and CSF samples were measured for HIV-1 RNA concentration using AMPLICOR (Roche) with a lower cutoff concentration of 400 copies/mL. For statistical analysis, the categoric variables at baseline were analyzed using the Fisher exact test, along with the independent and paired t test or the Mann-Whitney rank sum test. No significant statistical differences were observed between groups 1 and 2 considering gender, AIDS status, or clinical features.
All antiretroviral-naive patients had a detectable CSF viral load. Five (55.6%) of 9 patients from group 2 had an undetectable CSF viral load despite being more severely compromised. None had an undetectable plasma viral load together with a detectable CSF viral load. The CSF viral load concentration was 2.1 ± 0.6 log10 copies/mL higher in group 1 (Student t test, P = 0008). All patients had a decreased CSF viral load on second examination, most markedly in naive patients. All but 1 subject (patient 9 in group 2) had a normal CSF cytobiochemical examination. The CD4 cell level was similar for both groups, despite the fact that they had immunologic differences (P = 0.0021). The blood CD4 cell counts had no correlation with the detectable CSF viral load (P = 0.6).
Four patients had no neurologic abnormalities, and the remaining 15 cases (78.9%) had some criteria for encephalopathy (Centers for Disease Control and Prevention, 1994). During the follow-up period, 6 patients had no progression, whereas 9 improved up until the end of the study.
Of 19 patients enrolled, 12 (63.2%) underwent cerebral magnetic resonance imaging (MRI) and 9 (75%) had some abnormality: cortical atrophy (3 cases), periventricular hypersignal in T2 (2 cases), hydrocephaly (1 case), demyelination (2 cases), and corpus callosum atrophy (1 case).
In our study, the HIV-1 was detected from CSF in all patients not on treatment and in 4 (44.4%) of 9 patients undergoing treatment. This finding is concordant with those of other authors,1-7 who have reported the presence of HIV-1 during all stages of disease, because the central nervous system (CNS) has particular characteristics that make it a chronic sanctuary, protecting the virus against antiretroviral therapy and enabling its replication.
Of 14 of 19 patients from whom CSF was collected during the course of a second examination, 2 patients had an undetectable CSF HIV viral load and 12 had decreased CSF HIV RNA. Of these 12 patients, 7 received highly active antiretroviral therapy (HAART), and in 66.6%, the CSF HIV viral load later became undetectable, suggesting that antiretroviral therapy is the significant factor for decreasing the HIV load in the CNS, in line with other authors' findings.4,8-14 We observed a decreased CSF HIV viral load in 3 patients (patients 4 and 7 in group 1 and patient 9 in group 2) in only 5 months.
Our results highlight the importance of the difference between plasma and CSF compartments in our pediatric group, along with the integrity of the blood-brain barrier (BBB), as shown by the normal results of CSF biochemistry in all patients, probably attributable to HAART, which reduced traffic of lymphocytes across the BBB and improved immunologic responses, as occurs in adult patients.5,7,11,13-17,20
In the present work, we observed that only 44.4% of patients had a detectable CSF HIV viral load and 33.3% had undetectable HIV in plasma (group 2), probably because this group was more severely immunologically compromised and had more comorbidities, perhaps calling for a longer treatment period to demonstrate a decline in the HIV-1 viral load. We did not observe a statistical correlation between the CD4 cell count versus the plasma HIV load, the CD4 cell count versus the CSF HIV load (P = 0.603), or neurologic findings, given the small sample. Patient 4 (group 2) had cryptococcal meningitis as the first manifestation of AIDS 1 year previously, however, and had a high plasma HIV load, low CD4 cell count, and undetectable CSF HIV load without any neurologic symptomatology, along with excellent cognitive school performance. Therefore, we concluded the independence of the CD4 cell count and plasma HIV load.
The neurologic conditions with a high CSF HIV viral load include dementia and pediatric progressive encephalopathy.7,10-13,19-21 None of our patients worsened clinically during the present study. All those who had any symptoms of encephalopathy improved or became stable, independent of the CD4 cell count.
In contrast to some authors,2,3,6,13,18 we did not observe any abnormalities on CSF cytobiochemistry profiles in either group on examination, except those previously discussed.
The authors conclude that HIV-1 was present in the CSF of infected pediatric patients not receiving antiretroviral therapy even though they had no neurologic manifestations. In general, the study group remained stable from a clinical and neurologic standpoint in 33.3% of cases, whereas approximately 52% improved with regard to encephalopathy signs, mirroring results reported by other authors.20,21 The viral load in the CSF was lower than in the blood, although CSF viral load decay with antiretroviral therapy and plasma CD4 cell counts did not have any influence on this load.
Cristiane M. Rocha, MD*†
Daisy M. Machado, MD†
Maria Cecilia Sucupira, MD†
Regina C. Succi, MD†
*Casa de Saude Santa Marcelina São Paulo, Brazil
†Universidade Federal de São Paulo São Paulo, Brazil
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21. Rocha C, Gouvêa A, Machado D, et al. Manifestações neurológicas em crianças e adolescentes infectados e expostos pelo HIV-1. Arq Neuropsiquiatr
© 2007 Lippincott Williams & Wilkins, Inc.