Relationship of Virologic, Immunologic, and Clinical Parameters in Infants with Vertically Acquired Human Immunodeficiency Virus Type 1 Infection

Muñoz‐Fernández, María Ángeles; Obregón, Eva; Navarro, J.; Börner, Cristina; Gurbindo, María Dolores; Sampelayo, Teresa Hernández; Fernández‐Cruz, Eduardo

doi:10.1203/00006450-199610000-00014

Cited by 64 publications

(48 citation statements)

References 38 publications

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“…Between December 1984 and November 2000, 189 children who were born to HIV-1-infected mothers were diagnosed with vertical HIV-1 infection as previously described 16 and were followed from birth at the General University Hospital Gregorio Marañ ó n and Doce de Octubre Hospital in Madrid, Spain. HIV-1-infected infants were classified according to the Centers for Disease Control and Prevention guidelines.…”

Section: Study Subjectsmentioning

confidence: 99%

“…16,19 Briefly, peripheral blood mononuclear cells were isolated from blood by Ficoll-Hypaque density gradient centrifugation (Pharmacia, Uppsala, Sweden). Both viral culture and polymerase chain reaction assays were performed on the same sample.…”

Section: Virus Isolation and Determination Of Viral Phenotypementioning

confidence: 99%

“…20 We considered an isolate as syncytium-inducing (SI) when both formation of syncytia in MT-2 cell line under light microscopy and p24 antigen production in the culture supernatants were detected. 16 Moreover, as MT-2 cell line expresses CD4 receptor and CXCR4 (X4) coreceptor but not CCR5 (R5), this cell line may be useful to differentiate X4-using or SI from R5-using or non-SI strains. HIV BAL (R5 or non-SI) and HIV NL4.3 (X4 or SI) are routinely used as controls.…”

Section: Virus Isolation and Determination Of Viral Phenotypementioning

confidence: 99%

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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: Study Subjectsmentioning

confidence: 99%

Section: Virus Isolation and Determination Of Viral Phenotypementioning

confidence: 99%

Section: Virus Isolation and Determination Of Viral Phenotypementioning

confidence: 99%

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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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“…In vertically infected children, although little is known about viral load patterns, plasma viral load increases rapidly after birth, reaching a peak within the first 6 mo of age (37), thereafter followed by a decline during the first 5 y of life (38). Some authors (18,39) have reported that viral load during the first months of life may be a good surrogate marker of disease progression in perinatally infected infants. In our pediatric cohort, the initial viral burden determined during the first year of life was high without showing prognostic value; it was only after 6 mo of life that it tended to be associated with disease progression.…”

Section: Discussionmentioning

confidence: 99%

Relevance of Viral Phenotype in the Early AIDS Outcome of Pediatric HIV-1 Primary Infection

Kopka

2002

Pediatric Research

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“…VL was measured in 200 L plasma using a quantitative reverse PCR assay (Amplicor Monitor, Roche Diagnostics, Basel, Switzerland), with a sensitivity of 400 RNA copies/mL. T-lymphocyte subsets in peripheral blood were quantified by direct immunofluorescence using MAb of the T series and flow cytometry (FACScan, BD Biosciences, San Jose, CA, U.S.A.), as previously described (9).…”

Section: Patientsmentioning

confidence: 99%

Production of New T Cells by Thymus in Children: Effect of HIV Infection and Antiretroviral Therapy

Corrêa

Muñoz‐Fernández

2002

Pediatr Res

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The decrease in the number of CD4 ϩ T cells during HIV infection is the result of both peripheral destruction of cells by the virus and inadequate replacement of these cells. Aging and HIV infection lead to lower production of new T cells by the thymus, and, therefore, a complete restoration of the immune system is not generally achieved in infected adults after antiretroviral therapy. Because children have a completely functional thymus, we addressed the effects of HIV-1 infection on the production of new T cells in vertically infected children and whether the decrease of viral load after therapy results in a restoration of thymic function. To analyze the thymic function, T-cell receptor rearrangement excision circles were measured by quantitative PCR. Our results indicate that HIV-infected children have lower T-cell receptor rearrangement excision circle levels than age-matched uninfected children, likely due to an inhibitory effect of HIV on thymic function. Additionally, in some patients, the decrease in viral load after retroviral therapy allows the generation of new T cells by the thymus, thus recovering the normal number of CD4 cells. Depletion of CD4ϩ T cells is a hallmark of HIV infection (1). Experiments using human fetal thymus tissue implanted into SCID mice demonstrated that HIV can infect human thymocytes, leading to their death (2, 3). Therefore, the decrease in CD4 ϩ T cells in HIV-infected persons would be the result of two factors: peripheral CD4 ϩ T-cell depletion by the virus and insufficient replacement of the destroyed T cells (1).The thymus, the organ responsible for the maturation and selection of T cells, undergoes involution with age. It retains, however, a reduced ability to produce new T cells in adults (4). This thymic involution with age could be responsible for the rapid progression of HIV infection in older adults because of the difficulty of generating new T cells to replace CD4 ϩ T cells destroyed by the virus (5). In contrast, children have complete thymic function and, therefore, they have the capacity to regenerate all of the T-cell clones lost due to HIV infection, leading to a complete reconstitution of the immune system. Because T cells can have a very long life span, it is difficult to discriminate whether the "naive" T cells present in an individual are recently produced by the thymus or whether they arose from the division of cells formed in the first stages of life. Recently, Douek et al. (4) developed an assay that allows discrimination of the T cells of recent formation in the thymus from those of periphery expansion. This new assay was based on the mechanism by which the repertoire of the TCR is generated. In the genetic rearrangement of the regions V, D, and J that produce the ␣␤ TCR (6), the deletion of the TCRD locus forms some circles of DNA-denominated signal joint TREC (7,8). These circles are episomal and do not replicate during mitosis. Thus, TREC will be present only in recently produced cells by the thymus and not in those derived from the division or di...

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Relationship of Virologic, Immunologic, and Clinical Parameters in Infants with Vertically Acquired Human Immunodeficiency Virus Type 1 Infection

Cited by 64 publications

References 38 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

Relevance of Viral Phenotype in the Early AIDS Outcome of Pediatric HIV-1 Primary Infection

Production of New T Cells by Thymus in Children: Effect of HIV Infection and Antiretroviral Therapy

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