CD4+ T-Cell Immunodeficiency Is More Dependent on Immune Activation Than Viral Load in HIV-Infected Children on Highly Active Antiretroviral Therapy

Resino, Salvador; Seoane, Elena; Gutiérrez, M. Dolores Gurbindo; León, Juan Antonio; Muñoz‐Fernández, María Ángeles

doi:10.1097/01.qai.0000222287.90201.d7

Cited by 26 publications

(22 citation statements)

References 34 publications

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“…As opposed to what occurs in adults, these results suggest that CD38 is a marker of cell immaturity rather than cell activation in CD4 + T cells in children [37,38]. Finding that its expression is high in naive CD4 + T cells [39], that it decreases over time [40] and that it increases in CD4 + T cells during immune reconstitution [37,38] all support this concept. Besides representing a marker of cell immaturity, CD38 in CD4 + T cells is likely to have multiple functional activities [37].…”

Section: Cd38supporting

confidence: 65%

Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapy

Anselmi

Vendrame

Rampon

et al. 2007

Clinical and Experimental Immunology

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Section: Cd38supporting

confidence: 65%

Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapy

Anselmi

Vendrame

Rampon

et al. 2007

Clinical and Experimental Immunology

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“…Among those, a state of immune activation is probably the most striking and might have consequences not always immediately identified, but may result in distinct immune responses, including those to vaccine antigens previously reported by our group (37) and by others (6), with a higher humoral immune response to rubella (37) and lower cellular response to BCG (6). Some have even linked the state of immune activation, even more so than the viral load, to the destruction of CD4+ T cells and progression to AIDS in children (38) and adults (39). Further studies must address whether these findings could have an impact on the cellular immune responses to self and foreign antigens and result in clinical consequences to children born to HIV-1-infected mothers.…”

Section: Discussionmentioning

confidence: 95%

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

Ono

Santos

Succi

et al. 2008

Braz J Med Biol Res

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The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8%. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1%, P < 0.001; CD8+, 70.9 vs 79.6%, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7%, P < 0.001; CD8+, 8.6 vs 4.8%, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.

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“…3,4 Although current vaccine approaches are aimed at inducing effective neutralising antibodies, an increasing number of reports is documenting the lack of clinical efficacy of such antibodies in influencing the immunopathogenic processes triggered by HIV. 5 Even non-infectious virions and shed viral proteins can induce partial activation and apoptosis of lymphocytes.…”

Section: Current Treatment Statusmentioning

confidence: 99%

Pathogenesis of HIV: non-specific immune hyperactivity and its implications for vaccines

Cadogan

Dalgleish

2008

Clinical Medicine

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-More than a decade ago, the pathogenesis of AIDS was reviewed in this journal, using the subtitle 'classical and alternative views', when evidence was accumulating that HIV could not cause AIDS simply through direct cytopathic mechanisms alone. Generalised immune activation after infection with HIV is now understood to be associated with and predictive of disease progression and probably represents the single most important difference between rapid progression and slow or non-progression. However, the fundamental source of this phenomenon remains undetermined. Do pathogenic events after acute infection promote an environment susceptible to increased hyperactivity or does inherent reactivity towards HIV in susceptible individuals ultimately influence these processes? New strategies aimed at eliminating HIV-induced immune activation are required, as is investigation into the clinical and immunological influence of antibodies that target HIV epitopes associated with disease and that are not necessarily neutralising. Therapeutic vaccines to prevent disease may be more practical and effective than classic prophylactic vaccination.

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CD4+ T-Cell Immunodeficiency Is More Dependent on Immune Activation Than Viral Load in HIV-Infected Children on Highly Active Antiretroviral Therapy

Abstract: Our data suggest that elevated immune activation could be responsible for CD4(+) depletion rather than HIV replication because immunologic status is associated directly to immune activation and not to VL levels in HIV-infected children on HAART.

Cited by 26 publications

References 34 publications

Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapy

Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapy

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

Pathogenesis of HIV: non-specific immune hyperactivity and its implications for vaccines

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