Cerebrospinal fluid viral load is related to cortical atrophy and not to intracerebral calcifications in children with symptomatic HIV disease

Brouwers, Pirn; Civitello, Lucy; DeCarli, Charles; Wolters, Pamela L.; Sei, Shizuko

doi:10.3109/13550280009018303

Cited by 28 publications

(12 citation statements)

References 18 publications

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“…21,35,36 The suppression of HIV-1 replication is dependent on the presence of a relatively small number of HIV-1-specific CD8 ϩ Tlymphocyte clones, and it is possible that the duration of the neurologically asymptomatic phase for any given child may depend mostly on the magnitude of specific CD8 ϩ T-lymphocyte responses. 37 Thus, a decrease of CD8 ϩ T-lymphocytes would diminish the host capacity to control viral infection, as reported in animal models, 38 enabling infected macrophages to cross the blood-brain barrier. Compatible with this, HIV-1-infected macrophages by HIV-1-specific CTLs have been reported to be less effectively destroyed than HIV-1-infected CD4 ϩ Tlymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Low Blood CD8+ T-Lymphocytes and High Circulating Monocytes Are Predictors of HIV-1-Associated Progressive Encephalopathy in Children

et al. 2003

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ABSTRACT. Objective. Human immunodeficiency virus type 1 (HIV-1)-associated progressive encephalopathy (PE) is a common and devastating complication of HIV-1 infection in children, whose risk factors have not yet been clearly defined. Regardless of the age of presentation, PE shortens life expectancy. Paradoxically, as survival of patients has been prolonged as a result of the use of antiretroviral therapy, the prevalence of PE has increased. Therefore, a predictive marker of PE emergence is critical. The objective of this study was to determine in an observational study whether any immunologic (CD4 ؉ and CD8 ؉ T-lymphocyte counts, monocyte counts) or virologic (viral load [VL], biological characteristics of viral isolates) marker might be predictive of PE and whether any particular marker may be involved in the timing of clinical onset of PE.Methods. A total of 189 children who were vertically infected with HIV-1 were studied retrospectively, 58 of whom fulfilled criteria of the American Academy of Neurology for PE. T-lymphocyte subsets and monocytes in peripheral blood were quantified by flow cytometry. HIV-1 RNA was measured in plasma using a quantitative reverse transcriptase polymerase chain reaction assay. Demographic, clinical, and viro-immunologic characteristics in infants were compared with control groups using logistic regression. Proportions were compared using the 2 test or Fisher exact test. For each child, immunologic and virologic markers were analyzed in parallel closely before clinical onset of PE and closely after PE onset and compared by using the Student t test for paired samples.Results. Overall, mortality of 58 HIV-1-infected children who developed PE was significantly higher than of children who did not develop this complication. Blood CD8 ؉ T-lymphocytes <25% in the first months of life suggested a relative risk of progressing to PE 4-fold higher than those with CD8 ؉ >25% (95% confidence interval: 1.2-13.9) and remained statistically significant after adjustment for treatment. When we compared the PE-positive group with the acquired immunodeficiency syndrome (AIDS)/PE-negative group (children who developed clinical category C and without neurologic manifestations) in a cross-sectional study within 12 months before PE or AIDS diagnosis, respectively, the %CD8 ؉ T-lymphocytes were significantly lower in the PE-positive group. Normalized absolute counts of CD8 ؉ T-lymphocytes with respect to seroreverting children were significantly lower in the group of children with encephalopathy with respect to the AIDS/PE-negative group (data not shown). It is interesting that a statistically significant increase was observed in circulating monocyte percentages and absolute counts shortly before the first neurologic symptoms compared with values after PE was established and with those from HIV-1-infected controls. With respect to AIDS-related events, PE was strongly associated with anemia and lymphoid interstitial pneumonitis in the PE-positive group with respect to a group of children with AIDS but w...

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Section: Discussionmentioning

confidence: 99%

Low Blood CD8+ T-Lymphocytes and High Circulating Monocytes Are Predictors of HIV-1-Associated Progressive Encephalopathy in Children

et al. 2003

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“…One hypothesis posits that infected microglia, macrophages and activated astrocytes release a number of neurotoxins that then produce the observed diffuse neuronal damage (Kaul et al, 2001;Gonzalez-Scarano and Martin-Garcia, 2005). This then results in a number of motor and cognitive problems, with particularly severe consequences in children (Belman, 1997;Brouwers et al, 2000;Tamula et al, 2003). In the peripheral nervous system (PNS), HIV-1 replicates in macrophages that infiltrate peripheral nerves and is commonly associated with severe sensory neuropathies and pain (Luciano et al, 2003), and these symptoms may actually be enhanced by the antiviral drugs used for combating HIV-1 infection (HAART) (Sharma et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

HIV-1, chemokines and neurogenesis

Tran

Miller

2005

neurotox res

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HIV-1 infection of the brain results in a large number of behavioural defecits accompanied by diverse neuropathological signs. However,it is not clear how the virus produces these effects or exactly how the neuropathology and behavioural defecits are related. In this article we discuss the possibility that HIV-1 infection may negatively impact the process of neurogenesis in the adult brain and that this may contribute to HIV-1 related effects on the nervous system. We have previously demonstrated that the development of the dentate gyrus during embryogenesis requires signaling by the chemokine SDF-1 via its receptor CXCR4. We demonstrated that neural progenitor cells that give rise to dentate granule neurons express CXCR4 and other chemokine receptors and migrate into the nascent dentate gyrus along SDF-1 gradients.

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“…Other virological factors associated with HIV-associated CNS disease were detectable p24 antigen in mothers and infants [9], elevated plasma HIV RNA loads in the first year of life [5], and, for later-onset encephalopathy, high HIV RNA loads in CSF [9,14,15].…”

Section: H I V / a I D S M A J O R A R T I C L Ementioning

confidence: 99%

Early Immunological Predictors of Neurodevelopmental Outcomes in HIV‐Infected Children

Mekmullica¹,

Brouwers²,

Charurat³

et al. 2009

CLIN INFECT DIS

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Cerebrospinal fluid viral load is related to cortical atrophy and not to intracerebral calcifications in children with symptomatic HIV disease

Cited by 28 publications

References 18 publications

Low Blood CD8+ T-Lymphocytes and High Circulating Monocytes Are Predictors of HIV-1-Associated Progressive Encephalopathy in Children

Low Blood CD8+ T-Lymphocytes and High Circulating Monocytes Are Predictors of HIV-1-Associated Progressive Encephalopathy in Children

HIV-1, chemokines and neurogenesis

Early Immunological Predictors of Neurodevelopmental Outcomes in HIV‐Infected Children

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