Cytomegalovirus viraemia is associated with poor growth and T-cell activation with an increased burden in HIV-exposed uninfected infants

Garcia-Knight, Miguel; Nduati, Eunice; Hassan, Amin S.; Nkumama, Irene; Etyang, Timothy J.; Hajj, Naseem J.; Gambo, Faith; Odera, Denis; Berkley, James A.; Rowland‐Jones, Sarah; Urban, Britta C.

doi:10.1097/qad.0000000000001568

Cited by 19 publications

(24 citation statements)

References 62 publications

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“…HIV-exposed infants may be at higher risk of congenital CMV than HIV-unexposed infants ( 17 , 18 ). In HIV-exposed, uninfected infants, CMV infection may contribute to immune activation ( 11 , 19 , 20 ) and increase the risk of postnatal HIV infection ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Human Immunodeficiency Virus and Cytomegalovirus Infection on Infant Responses to Vaccines: A Review

2018

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The success of prevention of mother to child transmission programs over the last two decades has led to an increasing number of infants who are exposed to human immunodeficiency virus (HIV), but who are not themselves infected (HIV-exposed, uninfected infants). Although the morbidity and mortality among HIV-exposed, uninfected infants is considerably lower than that among HIV-infected infants, they may remain at increased risk of infections in the first 2 years of life compared with their HIV-unexposed peers, especially in the absence of breastfeeding. There is some evidence of immunological differences in HIV-exposed, uninfected infants, which could play a role in susceptibility to infection. Cytomegalovirus (CMV) may contribute to the increased immune activation observed in HIV-exposed, uninfected infants. Infants born to HIV-infected women are at increased risk of congenital CMV infection, as well as early acquisition of postnatal CMV infection. In infants with HIV infection, CMV co-infection in early life is associated with higher morbidity and mortality. This review considers how HIV infection, HIV exposure, and CMV infection affect infant responses to vaccination, and explores possible immunological and other explanations for these findings. HIV-infected infants have lower vaccine-induced antibody concentrations following tetanus, diphtheria, pertussis, hepatitis B, and pneumococcal vaccination, although the clinical relevance of this difference is not known. Despite lower concentrations of maternal-specific antibody at birth, HIV-exposed, uninfected infants respond to vaccination at least as well as their HIV-unexposed uninfected peers. CMV infection leads to an increase in activation and differentiation of the whole T-cell population, but there is limited data on the effects of CMV infection on infant vaccine responses. In light of growing evidence of poor clinical outcomes associated with CMV infection in HIV-exposed, uninfected infants, further studies are particularly important in this group. A clearer understanding of the mechanisms by which maternal viral infections influence the developing infant immune system is critical to the success of maternal and infant vaccination strategies.

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Section: Introductionmentioning

confidence: 99%

The Effect of Human Immunodeficiency Virus and Cytomegalovirus Infection on Infant Responses to Vaccines: A Review

2018

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“…Neurodevelopmental outcomes were also worse in HEU children [38], possibly due to exposures to other maternal infections during pregnancy [39,40] including coinfection with cytomegalovirus (CMV) [41][42][43][44].…”

Section: Introductionmentioning

confidence: 99%

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

Duri

Gumbo²,

Munjoma

et al. 2020

BMC Infect Dis

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Background Commencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+), has greatly improved maternal-infant health. Thus, large and increasing numbers of HIV-infected women are on ART during pregnancy, a situation concurrently increasing numbers of HIV-exposed-uninfected (HEU) infants. Compared to their HIV-unexposed-uninfected (HUU) counterparts, HEU infants show higher rates of adverse birth outcomes, mortality, infectious/non-communicable diseases including impaired growth and neurocognitive development. There is an urgent need to understand the impact of HIV and early life ART exposures, immune-metabolic dysregulation, comorbidities and environmental confounders on adverse paediatric outcomes. Methods Six hundred (600) HIV-infected and 600 HIV-uninfected pregnant women ≥20 weeks of gestation will be enrolled from four primary health centres in high density residential areas of Harare. Participants will be followed up as mother-infant-pairs at delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Clinical, socio-economic, nutritional and environmental data will be assessed for adverse birth outcomes, impaired growth, immune/neurodevelopment, vertical transmission of HIV, hepatitis-B/C viruses, cytomegalovirus and syphilis. Maternal urine, stool, plasma, cord blood, amniotic fluid, placenta and milk including infant plasma, dried blood spot and stool will be collected at enrolment and follow-up visits. The composite primary endpoint is stillbirth and infant mortality within the first two years of life in HEU versus HUU infants. Maternal mortality in HIV-infected versus -uninfected women is another primary outcome. Secondary endpoints include a range of maternal and infant outcomes. Sub-studies will address maternal stress and malnutrition, maternal-infant latent tuberculosis, Helicobacter pylori infections, immune-metabolomic dysregulation including gut, breast milk and amniotic fluid dysbiosis. Discussion The University of Zimbabwe-College of Health-Sciences-Birth-Cohort study will provide a comprehensive assessment of risk factors and biomarkers for HEU infants’ adverse outcomes. This will ultimately help developing strategies to mitigate effects of maternal HIV, early-life ART exposures and comorbidities on infants’ mortality and morbidity. Trial registration ClinicalTrial.gov Identifier: NCT04087239. Registered 12 September 2019.

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“…Maternal coinfection with HIV, even when mitigated by antiretroviral treatment, is associated with higher CMV viral loads in plasma, saliva, cervix and breast milk, and a greater risk of both congenital and postnatal CMV transmission [4][5][6][7]. Numerous studies have highlighted the negative health impacts of CMV on both HIV-infected and HIV-exposed uninfected (HEU) infants and children [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants

Pang

Slyker

Roy

et al. 2020

Preprint

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Cytomegalovirus (CMV) is the most congenital infection (cCMVi), and is particularly common among infants born to HIV-infected women. Studies of cCMVi pathogenesis are complicated by the presence of multiple infecting maternal CMV strains, especially in HIV-positive women, and the large, recombinant CMV genome. Using newly-developed tools to reconstruct CMV haplotypes, we demonstrate anatomic CMV compartmentalization in five HIV-infected mothers, and identify the possibility of congenitally-transmitted genotypes in three of their infants. A single CMV strain was transmitted in each congenitally-infected case, and all were closely related to those that predominate in the cognate maternal cervix. Compared to non-transmitted strains, these congenitally-transmitted CMV strains showed statistically significant similarities in 19 genes associated with tissue-tropism and immunomodulation. In all infants, incident superinfections with distinct strains from breast milk were captured during follow-up. The results represent potentially important new insights into the virologic determinants of early CMV infection.

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Cytomegalovirus viraemia is associated with poor growth and T-cell activation with an increased burden in HIV-exposed uninfected infants

Cited by 19 publications

References 62 publications

The Effect of Human Immunodeficiency Virus and Cytomegalovirus Infection on Infant Responses to Vaccines: A Review

The Effect of Human Immunodeficiency Virus and Cytomegalovirus Infection on Infant Responses to Vaccines: A Review

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants

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