Early Prognostic Indicators in Primary Perinatal Human Immunodeficiency Virus Type 1 Infection: Importance of Viral RNA and the Timing of Transmission on Long-Term Outcome

Re, Dickover; Dillon, Maryanne; Leung, Ka Man; Krogstad, Paul; Plaeger, Susan; Kwok, Shirley; Christopherson, Cindy; Deveikis, Audra; Keller, Margaret; Er, Stiehm; Yj, Bryson

doi:10.1086/515637

Cited by 81 publications

(49 citation statements)

References 30 publications

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“…Indeed, in our study, most children who were infected in utero had relatively low levels of HIV-1 RNA at birth, as compared with initial positive HIV-1 RNA VL obtained in children who were infected later. This finding is consistent with previous studies conducted in industrialized countries (where a proportion of infants and their mothers during pregnancy received ARV treatment) 11,12 and in Africa as well. For instance, among 135 untreated children from Malawi, Biggar et al 24 obtained a median level in 24 cord blood-positive samples of 4.89 log 10 copies/mL, significantly lower than levels in the first positive samples of 52 cord blood-negative perinatally infected children (median: 5.55 log 10 copies/ mL).…”

Section: Discussionsupporting

confidence: 93%

“…36 Despite the vast differences between subSaharan Africa and industrialized countries (in terms of viral, immunologic, environmental, and nutritional factors, and route of exposure including the additional risk linked to breastfeeding and access to ARV therapy), our findings corroborate and extend in a striking manner studies performed previously in the developed world 11,12,16,17 that observed a unique pattern of viral replication in infected children. In adults, during the period of primary infection, HIV-1 RNA copy number initially rises to high peak levels, rapidly followed by a 2-to 3-log 10 decrease until reaching a steady-state plateau (the virologic "setpoint") within approximately 6 to 9 months after the acquisition of HIV infection.…”

Section: Discussionsupporting

confidence: 80%

“…The mother's HIV-1 RNA level at delivery was also an independent prognostic factor for the pediatric risk of developing AIDS or death, in agreement with previous studies. 11,40 More surprising, although we were not able to identify significant differences in HIV-1 RNA levels between boys and girls at a given age, progression to AIDS or death seemed to be significantly different by sex and was more rapid for girls than for boys. In adults, lower HIV-1 RNA VLs have been described for women than for men, but the implications of these findings on disease progression remain unclear.…”

Section: Discussionmentioning

confidence: 73%

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Pediatric Viral Human Immunodeficiency Virus Type 1 RNA Levels, Timing of Infection, and Disease Progression in African HIV-1-Infected Children

Raffi

Sakarovitch²,

Msellati³

et al. 2003

Pediatrics

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ABSTRACT. Objective. To describe plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in African HIV-1-infected children in relation to the timing of infection and disease progression.Methods. A retrospective cohort study was conducted of 80 children who were born to HIV-1-positive mothers and clinically followed from birth to 18 months of age in the ANRS 049 Ditrame project, Abidjan, Cô te d'Ivoire (West Africa). The diagnosis and timing of pediatric HIV-1 infection were determined prospectively according to HIV-1 DNA polymerase chain reaction results. A total of 364 HIV-1 RNA viral load (VL) measurements were assessed retrospectively. Kaplan-Meier analyses and proportional hazards models were used to evaluate the prognostic value of pediatric VL and covariates for HIV disease progression or death.Results. Mean initial positive VL was significantly lower among children who were infected in utero (4.94 log 10 /mL, n ‫؍‬ 12) than in children who were infected later (5.6 -6.1 log 10 /mL, n ‫؍‬ 68). In the first 6 months after diagnosis, HIV-1 RNA levels peaked (>6 log 10 /mL), regardless of timing of infection. Then, a slow decline (overall slope, ؊0.076 log 10 copies/mL/mo) was observed until 18 months of age. A 1 log 10 higher value of the pediatric peak VL (risk ratio [

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 73%

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Pediatric Viral Human Immunodeficiency Virus Type 1 RNA Levels, Timing of Infection, and Disease Progression in African HIV-1-Infected Children

Raffi

Sakarovitch²,

Msellati³

et al. 2003

Pediatrics

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“…The remaining infected children display a later onset of symptoms but nevertheless die within 5 to 10 years. Interestingly, most of these long-surviving children maintain a persistently high viremia and normal CD4 ϩ lymphocyte levels for many months following infection (1,10,35); this clinical picture sharply contrasts with the rapid clearance of HIV-1 viremia that is typical of adult infection. The sustained high-level viremia in infected children may result from persistent viral replication within the progressively expanding lymphoid cell mass (24), including the thymus, which represents the principal source of T lymphopoiesis during early life (15).…”

mentioning

confidence: 99%

Induction of Simian AIDS in Infant Rhesus Macaques Infected with CCR5- or CXCR4-Utilizing Simian-Human Immunodeficiency Viruses Is Associated with Distinct Lesions of the Thymus

Reyes¹,

Canfield

Esser

et al. 2004

J Virol

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Newborn rhesus macaques were infected with two chimeric simian-human immunodeficiency virus (SHIV) strains which contain unique human immunodeficiency virus type 1 (HIV-1) env genes and exhibit distinct phenotypes. Infection with either the CCR5-specific SHIV SF162P3 or the CXCR4-utilizing SHIV SF33A resulted in clinical manifestations consistent with simian AIDS. Most prominent in this study was the detection of severe thymic involution in all SHIV SF33A -infected infants, which is very similar to HIV-1-induced thymic dysfunction in children who exhibit a rapid pattern of disease progression. In contrast, SHIV SF162P3 induced only a minor disruption in thymic morphology. Consistent with the distribution of the coreceptors CXCR4 and CCR5 within the thymus, the expression of SHIV SF162P3 was restricted to the thymic medulla, whereas SHIV SF33A was preferentially detected in the cortex. This dichotomy of tissue tropism is similar to the differential tropism of HIV-1 isolates observed in the reconstituted human thymus in SCID-hu mice. Accordingly, our results show that the SHIV-monkey model can be used for the molecular dissection of cell and tissue tropisms controlled by the HIV-1 env gene and for the analysis of mechanisms of viral immunopathogenesis in AIDS. Furthermore, these findings could help explain the rapid progression of disease observed in some HIV-1-infected children.

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“…P revious studies of HIV-1-infected infants have shown either the presence or absence of HIV-1 RNA at birth, and the magnitude and duration of early viremia are predictive of the long-term clinical outcome (1,2). The long-term survivors of perinatal HIV-1 infection are a special group of chronically infected children and adolescents critical to enhanced understanding of perinatal HIV-1 infection.…”

mentioning

confidence: 99%

Pediatric HIV-1–Specific Cytotoxic T-Lymphocyte Responses Suggesting Ongoing Viral Replication Despite Combination Antiretroviral Therapy

et al. 2007

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Human immunodeficiency virus-1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses are common in infected adults and usually exhibit rapid decay after combination antiretroviral therapy (ART). CTLs develop later in the first year of life, and the fate of HIV-1-specific responses in perinatally infected children after ART is less well described. HIV-1-specific CTL responses were measured in 17 perinatally infected children and adolescents (ages 3-20 y) receiving combination ART. Seven had prolonged viral suppression (Ͻ400 copies/mL) for 2.5-5.3 y and 10 had persistent viremia (median, 77,550 copies/mL). HIV-1-specific CTL responses were tested by interferon (IFN)-␥ enzyme-linked immunospot (ELISpot) assays using 53 overlapping peptide pools spanning the entire HIV-1 proteome. HIV-1-specific CTL responses were detected in 14 of 17 individuals. Responses to one to four viral proteins were found in eight of 10 individuals with persistent viremia and six of seven with prolonged viral suppression. The magnitude and breadth of CTL responses were similar between groups. HIV-1-specific CTL responses were present in the majority of perinatally infected subjects, irrespective of viremia at evaluation. Because ART-treated infected adults usually have rapid decay of responses, these data suggest viral replication below the limits of detection is more persistent in combination ART-treated perinatally infected pediatric subjects. The long-term clinical implications of these findings remain to be determined. (Pediatr Res 61: 692-697, 2007)

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Early Prognostic Indicators in Primary Perinatal Human Immunodeficiency Virus Type 1 Infection: Importance of Viral RNA and the Timing of Transmission on Long-Term Outcome

Cited by 81 publications

References 30 publications

Pediatric Viral Human Immunodeficiency Virus Type 1 RNA Levels, Timing of Infection, and Disease Progression in African HIV-1-Infected Children

Pediatric Viral Human Immunodeficiency Virus Type 1 RNA Levels, Timing of Infection, and Disease Progression in African HIV-1-Infected Children

Induction of Simian AIDS in Infant Rhesus Macaques Infected with CCR5- or CXCR4-Utilizing Simian-Human Immunodeficiency Viruses Is Associated with Distinct Lesions of the Thymus

Pediatric HIV-1–Specific Cytotoxic T-Lymphocyte Responses Suggesting Ongoing Viral Replication Despite Combination Antiretroviral Therapy

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