Maternal plasma and breastmilk viral loads are associated with HIV-1-specific cellular immune responses among HIV-1-exposed, uninfected infants in Kenya

Liu, Amy; Lohman-Payne, Barbara; Chung, Michael H.; Kiarie, James; Kinuthia, John; Slyker, Jennifer A.; Richardson, Barbra A.; Lehman, Dara A.; Farquhar, Carey; John‐Stewart, Grace

doi:10.1111/cei.12599

Cited by 8 publications

(4 citation statements)

References 49 publications

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“…These findings suggest that inflammation in HEU infants may be driven in part by exposure to HIV viremia, rather than exposure to an immunosuppressed intrauterine environment per se. Exposure to HIV products across the placenta is consistent with prior studies that have shown evidence of HIV-specific T-cell responses in HEU infants [ 16 ]. We hypothesize that exposure to HIV products modulates the developing immune system, either leading directly to infant inflammation or priming the immune system to generate exaggerated inflammatory responses to infection.…”

Section: Discussionsupporting

confidence: 87%

CMV acquisition and inflammation in HIV-exposed uninfected Zimbabwean infants

et al. 2016

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Cytomegalovirus (CMV) acquisition and inflammation were evaluated in 231 human immunodeficiency virus (HIV)–exposed uninfected (HEU) and 100 HIV-unexposed Zimbabwean infants aged 6 weeks. The HEU and HIV-unexposed infants had a similarly high prevalence of CMV (81.4% vs 74.0%, respectively; P = .14), but HEU infants had higher CMV loads (P = .005) and >2-fold higher C-reactive protein (CRP) concentrations (P < .0001). The CMV-positive HEU infants had higher CRP than the CMV-negative HEU infants; this association disappeared after adjusting for maternal HIV load. Overall, CMV acquisition is high in early life, but HEU infants have higher CMV loads and a proinflammatory milieu, which may be driven partly by maternal HIV viremia.

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Section: Discussionsupporting

confidence: 87%

CMV acquisition and inflammation in HIV-exposed uninfected Zimbabwean infants

et al. 2016

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“…Additionally, because of shared HLA alleles the transmitted virus may be preadapted to escape CD8+ T cells targeting HIV epitopes restricted by HLA alleles inherited from the mother further complicating pediatric HIV-1 infection ( 200 , 201 ). HIV-specific cellular immune responses are detected in exposed uninfected infants, but their role in influencing virus acquisition is uncertain ( 202 , 203 ).…”

Section: Factors Influencing Vertical Transmissionmentioning

confidence: 99%

Understanding Viral and Immune Interplay During Vertical Transmission of HIV: Implications for Cure

et al. 2021

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Despite the significant progress that has been made to eliminate vertical HIV infection, more than 150,000 children were infected with HIV in 2019, emphasizing the continued need for sustainable HIV treatment strategies and ideally a cure for children. Mother-to-child-transmission (MTCT) remains the most important route of pediatric HIV acquisition and, in absence of prevention measures, transmission rates range from 15% to 45% via three distinct routes: in utero, intrapartum, and in the postnatal period through breastfeeding. The exact mechanisms and biological basis of these different routes of transmission are not yet fully understood. Some infants escape infection despite significant virus exposure, while others do not, suggesting possible maternal or fetal immune protective factors including the presence of HIV-specific antibodies. Here we summarize the unique aspects of HIV MTCT including the immunopathogenesis of the different routes of transmission, and how transmission in the antenatal or postnatal periods may affect early life immune responses and HIV persistence. A more refined understanding of the complex interaction between viral, maternal, and fetal/infant factors may enhance the pursuit of strategies to achieve an HIV cure for pediatric populations.

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“…Fetal immune activation may result from direct exposure to HIV in utero ; notably, HEU infants have evidence of HIV-specific T-cell responses ( 27 , 28 ), suggestive of in utero sensitization. These responses are greater in infants born to mothers with high compared to low viral loads ( 29 ). Direct exposure to HIV or its components at a critical time of T-cell development in utero may contribute to the T-cell abnormalities described.…”

Section: Morbidity and Mortality Of Heu Infantsmentioning

confidence: 99%

HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era

et al. 2016

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The ZVITAMBO trial recruited 14,110 mother–infant pairs to a randomized controlled trial of vitamin A between 1997 and 2000, before the availability of antiretroviral therapy for HIV prophylaxis or treatment in Zimbabwe. The HIV status of mothers and infants was well characterized through 1–2 years of follow-up, leading to the largest cohort to date of HIV-exposed uninfected (HEU) infants (n = 3135), with a suitable comparison group of HIV-unexposed infants (n = 9510). Here, we draw on 10 years of published findings from the ZVITAMBO trial. HEU infants had increased morbidity compared to HIV-unexposed infants, with 50% more hospitalizations in the neonatal period and 30% more sick clinic visits during infancy, particularly for skin infections, lower respiratory tract infections, and oral thrush. HEU children had 3.9-fold and 2.0-fold higher mortality than HIV-unexposed children during the first and second years of life, respectively, most commonly due to acute respiratory infections, diarrhea/dysentery, malnutrition, sepsis, and meningitis. Infant morbidity and mortality were strongly related to maternal HIV disease severity, and increased morbidity remained until maternal CD4 counts were >800 cells/μL. HEU infants were more likely to be premature and small-for-gestational age than HIV-unexposed infants, and had more postnatal growth failure. Here, we propose a conceptual framework to explain the increased risk of infectious morbidity, mortality, and growth failure among HEU infants, hypothesizing that immune activation and inflammation are key drivers of both infection susceptibility and growth failure. Future studies should further dissect the causes of infection susceptibility and growth failure and determine the impact of ART and cotrimoxazole on outcomes of this vulnerable group of infants in the current era.

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Maternal plasma and breastmilk viral loads are associated with HIV-1-specific cellular immune responses among HIV-1-exposed, uninfected infants in Kenya

Cited by 8 publications

References 49 publications

CMV acquisition and inflammation in HIV-exposed uninfected Zimbabwean infants

CMV acquisition and inflammation in HIV-exposed uninfected Zimbabwean infants

Understanding Viral and Immune Interplay During Vertical Transmission of HIV: Implications for Cure

HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era

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