Repeatedly positive human immunodeficiency virus type 1 DNA polymerase chain reaction in human immunodeficiency virus-exposed seroreverting infants

Three human immunodeficiency virus type 1 (HIV-1)exposed children who had repeatedly positive DNA polymerase chain reaction (PCR) tests for HIV in ≥:5 samples before seroreversion to HIV-negative status are reported. The children belong to a cohort of 210 infants who were born to HIV-infected mothers and were tested at intervals of 1 to 3 months by HIV viral culture, PCR, and p24 antigen; only the PCR was positive in ≥5 samples in the children reported here. Their clinical features were indistinguishable from other seroreverters. All three children had a transient drop in CD4:CD8 ratio to <1.0. The transiently positive DNA PCR in HIV-exposed infants may indicate either that HIV infection was eliminated by a strong host immune response or that infection was caused by an attenuated/defective strain of virus

Immunophenotypic analysis of HIV‐infected children: Alterations within the first year of life, changes with disease progression, and longitudinal analyses of lymphocyte subsets

Perinatal infection with human immunodeficiency virus (HIV) results in tremendous activation of the pediatric immune system. An important component of understanding the pathogenesis of this disease is to characterize and quantify antigenic indicators of activation within the peripheral lymphocyte population. We measured T‐lymphocyte activation and maturation antigens in a cohort of 112 HIV‐infected children treated with antiretroviral therapy according to the current standard of care. Changes in expression of CD95, HLA‐DR, and CD45RO were evident in 22 HIV‐infected children younger than 1 year of age. A comparison of phenotypic profiles of children in mild, moderate, and severe immune categories revealed perturbations of CD28, CD38, CD45RA, CD45RO, CD95, and HLA‐DR. Finally, a novel analysis of 56 HIV‐infected children based on the repeated collection of data over time (median of seven observations over 33 months) demonstrated a strong negative correlation between the percentage CD4 and the percentage of CD45RO, CD95, and HLA‐DR on both CD4 and CD8 cells. Our data implicate persistent immune activation, beginning within the first year of life, as a major driving force in the pathogenesis of perinatally acquired HIV disease. Cytometry (Comm. Clin. Cytometry) 46:157–165, 2001. © 2001 Wiley‐Liss, Inc

Immunophenotypic Analysis of Peripheral Blood Mononuclear Cells Undergoing In Vitro Apoptosis After Isolation From Human Immunodeficiency Virus–Infected Children

Abstract Lymphocytes of human immunodeficiency virus (HIV)-infected individuals undergo accelerated apoptosis in vitro, but the subsets of cells affected have not been clearly defined. This study examined the relationship between lymphocyte phenotype and apoptotic cell death in HIV-infected children by flow cytometry. Direct examination of the phenotype of apoptotic lymphocytes was accomplished using a combination of surface antigen labeling performed simultaneously with the Tdt mediated Utp nick end-labeling (TUNEL) assay. In comparison to live cells, apoptotic lymphocytes displayed an overrepresentation of CD45RO and HLA-DR expressing cells, while CD28 and CD95 expressing cells were underrepresented. Lymphocytes expressing CD4, CD8, and CD38 were equally represented in apoptotic and live populations. When percent lymphocyte apoptosis follow- ing culture was examined independently with lymphocyte subsets in fresh blood, apoptosis was negatively correlated with the percentage of CD4 cells, but not with specific CD4 T-cell subsets. Although not correlated with the percentage of total CD8 cells, apoptosis was positively correlated with specific CD8 T-cell subsets expressing CD45RO and CD95 and negatively correlated for CD8 T cells expressing CD45RA. These results provide direct evidence that a population of activated lymphocytes with the memory phenotype lacking the costimulatory molecule CD28 are especially prone to undergo apoptosis. The findings related to CD95 expression in fresh and apoptotic cells implicate Fas-dependent and Fas-independent pathways of apoptosis in HIV disease in children

Distribution of CCR5Δ32 in Human Immunodeficiency Virus-Infected Children and Its Relationship to Disease Course

Homozygosity for a 32-bp deletion in the CCR5 gene (CCR5Δ32) has been shown to confer resistance to infection with the macrophage-tropic strain of human immunodeficiency virus (HIV) type 1. We examined the distribution of CCR5Δ32 in 47 children (age range, 1.5 to 19 years), of whom 43 were infected with HIV, by the perinatal route (n = 41) or by the intravenous route (n = 2). The infected patients were classified as rapid progressors (RP) (n = 7) (CDC category C3 or death by 2 years of age), non-rapid progressors (NRP) (n = 17) (survival for ≥8 years after infection), or intermediate (n = 19). CCR5Δ32 heterozygosity was found in two HIV-infected children, both NRP. None of the subjects were homozygous for CCR5Δ32, and the remaining children had no evidence of CCR5Δ32. The presence of CCR5Δ32 heterozygosity in 4.8% of this, predominantly non-Caucasian population is consistent with the published distribution of the mutation. The finding that CCR5Δ32 was present only in NRP and not in any RP is in agreement with previous reports suggesting that heterozygosity for CCR5Δ32 may confer limited protection from disease progression

CD95 Expression and Apoptosis during Pediatric HIV Infection: Early Upregulation of CD95 Expression

Pediatric HIV infection is characterized by a progressive decline in CD4 T lymphocytes and faster disease progression than is typically seen in adults. Apoptosis, possibly mediated through the CD95 antigen, has been proposed as a mechanism for cell loss which eventually leads to immune dysfunction. In this study of peripheral blood lymphocytes from HIV-infected children, classified according to CDC immunologic categories, we found that the percentage of CD4 and CD8 T cells expressing CD95 and the percentage of lymphocytes undergoing apoptosis were increased in children with HIV infection and were greater in children from immunologic Category III as compared to those in Category I. Most striking was our observation that an increased percentage of CD95-positive cells appeared as early as 3 months of age, at a time when these children did not have elevated levels of apoptosis. These data demonstrate early upregulation of CD95 expression in HIV-infected infants, an abberation which may have profound implications for the pathogenesis of perinatally acquired HIV disease