Placental Immunologic Differences by Maternal HIV Status in Pune, India
Overview
This study from the PRACHITi cohort in Pune, India, found that maternal HIV infection is associated with decreased placental FcRn expression and increased placental CD8+ T-cell abundance, regardless of viral suppression. These immunologic alterations may contribute to poorer infant outcomes despite effective antiretroviral therapy and absence of mother-to-child HIV transmission.
Background
Globally, 1.4 million pregnant women live with HIV, most receiving antiretroviral therapy (ART) during pregnancy. While ART reduces mother-to-child transmission, infants exposed to HIV but uninfected (iHEU) have higher risks of infections and immune alterations compared to unexposed infants. The placenta mediates maternal-fetal immune interactions, and HIV-associated placental inflammation can impair antibody transfer via the neonatal Fc receptor (FcRn). It remains unclear if ART-mediated viral suppression normalizes placental immune function and FcRn expression.
Data Highlights
Parameter
Women with HIV (n=18)
Women without HIV (n=24)
P Value
Median gestational age at delivery (weeks)
38.3 (IQR 37.5–39.1)
38.3 (IQR 37.5–39.1)
Not specified
Median CD4 count at entry (cells/mm3)
455 (IQR 281–640)
Not applicable
Not applicable
Median CD4 count at delivery (cells/mm3)
429 (IQR 317–686)
Not applicable
Not applicable
Number with undetectable viral load (≤40 copies/mL)
10
Not applicable
Not applicable
Median viral load if detectable (copies/mL)
151 (IQR 118.15–539,334)
Not applicable
Not applicable
Relative placental FcRn expression (median)
0.54
0.84
0.01
Placental CD8+ T-cell abundance
Significantly higher
Lower
Significant
Key Findings
Placental FcRn expression was significantly lower in women living with HIV compared to HIV-negative women (median 0.54 vs 0.84, P = .01).
Lower FcRn expression was not correlated with maternal CD4 count or viral load levels.
Women with HIV had significantly increased placental CD8+ T-cell infiltration regardless of viral suppression status.
All women living with HIV were on combined ART, with over half achieving viral suppression.
Placental immune dysregulation persisted despite ART and viral suppression, suggesting incomplete reversal of HIV-associated placental inflammation.
Clinical Implications
These findings highlight that maternal HIV infection can alter placental immune environment and antibody transfer mechanisms even when viral replication is controlled by ART. Clinicians should be aware that infants exposed to HIV in utero may remain at increased risk for infectious morbidity due to impaired placental function. Strategies to monitor and support immune health in these infants are warranted.
Conclusion
Maternal HIV infection is associated with decreased placental FcRn expression and increased CD8+ T-cell infiltration, independent of viral suppression, potentially contributing to adverse infant outcomes. Further research is needed to understand mechanisms and improve interventions for infants exposed to HIV.
References
PRACHITi Cohort Study, Pune, India -- Differences in Placental Immunology Associated with HIV
by Jyoti S Mathad, Mallika Alexander, Ramesh Bhosale, Shilpa Naik, Lisa Marie Cranmer, Vandana Kulkarni, Sydney Busch, Andrea Chalem, Emily Gitlin, Jun Lei, Anguo Liu, Jin Liu, Yang Liu, Rupak Shivakoti, Amita Gupta, Irina Burd
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