Low Immune Activation in Early Pregnancy Is Associated With Preterm But Not Small-for-gestational-age Delivery in Women Infected With Human Immunodeficiency Virus Initiating Antiretroviral Therapy in Pregnancy: A Prematurity Immunology in HIV-infected Mothers and their Infants Study (PIMS) Case-control Study in Cape Town, South Africa
Year: 2021
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Mechanisms underlying an association between human immunodeficiency virus (HIV) or antiretroviral therapy (ART) during pregnancy with risk of preterm delivery (PTD) and small-for-gestational-age (SGA) remain unclear. We explored the association between cellular immune activation and PTD or SGA in women with HIV initiating ART during or before pregnancy. METHODS: Women with HIV enrolled at median 15 weeks' gestation, were analyzed for immune markers, and matched on ART initiation timing (15 women initiated pre- and 15 during pregnancy). There were 30 PTD (delivery <37 weeks), 30 SGA (weight for age ≤10th percentile) cases, and 30 controls (term, weight for gestational age >25th percentile) as outcomes. Lymphocytes, monocytes, and dendritic cell populations and their activation status or functionality were enumerated by flow cytometry. RESULTS: PTD cases initiating ART in pregnancy showed decreased CD8+ T cell, monocyte, and dendritic cell activation; increased classical (CD14+CD16-) and intermediate (CD14+CD16+) monocyte frequencies; and decreased inflammatory monocytes (CD14dimCD16+) compared with SGA cases and term controls (all P < .05). Allowing for baseline viral load, the immune markers remained significantly associated with PTD but only in women initiating ART in pregnancy. Lower monocyte activation was predictive of PTD. TLR ligand-induced interferon-α and macrophage inflammatory protein-1β levels in monocytes were significantly lower in PTD women initiating ART in pregnancy. CONCLUSION: Low immune activation, skewing toward anti-inflammatory monocytes, and lower monocyte cytokine production in response to TLR ligand stimulation were associated with PTD but not SGA among women initiating ART in, but not before, pregnancy, suggesting immune anergy to microbial stimulation as a possible underlying mechanism for PTD in women initiating ART in pregnancy.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciab151
Institutions: University of KwaZulu-Natal, University of the Witwatersrand, National Institute for Communicable Diseases, University of Cape Town, Africa Health Research Institute, Institute of Infectious Disease and Molecular Medicine, Leibniz Institute of Virology (LIV), University of Southampton, Ragon Institute of MGH, MIT and Harvard, Max Planck Institute for Infection Biology, University College London
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,052
Funders: U.S. President’s Emergency Plan for AIDS Relief, Wellcome Trust, Government of the United Kingdom, National Research Foundation, South African Medical Research Council, New Partnership for Africa's Development, African Academy of Sciences, National Institutes of Health, Medical Research Council, Alliance for Accelerating Excellence in Science in Africa, Fogarty International Center, National Institute of Child Health and Human Development, Office of AIDS Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Strategies to optimize ART services for maternal&child health: the MCH-ART study, G2415674080, G2444244560, G2989112569, G3000957577, G3335251837, G4156438909, ART and risk of preterm delivery in a rural high HIV prevalence area, Sub-Saharan African Network for TB/HIV research Excellence (SANTHE), G5901762629, G6590892262, G6617178558, G6675272361, G6868616705, G7013806573, G7238354678, G8119020889, G8183321107, Fogarty Global Health Fellows Coordinating Center, G8445079486, G8488937646, G8547154903, Sub-Saharan African Network for TB/HIV research Excellence (SANTHE)
OpenAlex ID: W3130481801