Maternal HIV Infection as a Risk Factor for Primary Epstein-Barr Virus Infection in Kenyan Infants

Human immunodeficiency virus (HIV) infection is known to be associated with EBV shedding in saliva suggesting an increased risk of EBV transmission to infants born to mothers with HIV at an earlier age. In this study we investigated (i) whether maternal HIV status was a risk factor for EBV in blood at delivery or for shedding in saliva and breast milk of 6- and 10-weeks post-partum mothers, (ii) if there was a difference in EBV strains shed between HIV+ and HIV- mothers, and (iii) if maternal HIV status was a determinant of EBV viral load in their infants. Samples were collected as part of a prospective cohort study that followed HIV-positive (HIV+) and HIV-negative (HIV-) pregnant women in Western Kenya through delivery and post-partum period. EBV viral load in blood was found to be significantly higher in mothers with HIV (p-value = 0.04). Additionally, a statistically significant difference was observed between EBV viral load in saliva samples and HIV status where HIV+ mothers had a higher EBV viral load in saliva at 6-weeks post-partum compared to HIV- mothers (p-value < 0.01). The difference in EBV shedding in breast milk was not found to be statistically significant. Furthermore, no difference in frequency of EBV strain was attributable to HIV- or HIV+ mothers. Interestingly, we found that infants born to HIV+ mothers had a higher EBV viral load at the time of their first EBV detection in blood than infants born to HIV- mothers and this was independent of age at detection. Overall, our study suggests that HIV infected mothers shed more virus in saliva than HIV-negative mothers and infants born to HIV+ mothers were at risk for loss of control of primary EBV infection as evidenced by higher EBV viral load following primary infection.

Fetal-maternal surgery for spina bifida in a HIV-infected mother

INTRODUCTION: In select cases, in utero surgery for MMC leads to better outcomes than postnatal repair. However, maternal HIV infection constitutes a formal exclusion criterion due to the potential of vertical HIV transmission. Encouraged by a previous case of a successful fetal spina bifida repair in a Hepatitis Bs antigen positive woman, a plan was devised allowing for fetal surgery. CASE REPORT: In utero MMC repair was performed although the mother was HIV-infected. To minimize the risk of in utero HIV transmission, the mother was treated by HAART throughout gestation as well as intravenous zidovudine administration during maternal-fetal surgery. The mother tolerated all procedures very well without any sequelae. The currently 20 month-old toddler, is HIV negative and has significantly benefitted from fetal surgery. DISCUSSION/CONCLUSION: This case shows that maternal HIV is not a priori a diagnosis that excludes fetal surgery. Rather, it might be a surrogate for moving towards personalized medicine and away from applying too rigorous exclusion criteria in the selection of candidates for maternal-fetal surgery.

Placental Heterogeneity in Stillbirth and Its Relations to Maternal Exogenous Characteristics

Introduction: Heterogeneous patterns of placental lesions in stillbirth signal important variations in placental histopathology that may be diagnostic in stillbirth. We explore placental heterogeneity and its associations with maternal characteristics (including HIV) using latent class analysis. Methods: Placental and maternal data and slides were assessed retrospectively for 122 confirmed stillbirths (gestational age ≥ 28 weeks) delivered at a major South African academic hospital between January 2016–July 2018. The slides were reviewed by 2 pathologists and classified using the Amsterdam Consensus Classification System. Latent class analyses were conducted on raw data. Results: We identify 5 latent placental classes in stillbirth based on similarity in patterns of observed diagnostic criteria and their associations with maternal characteristics. Three classes bear similarity to generalized patterns of placental injury identified previously. Our study shows that intrauterine infection was the commonest histopathological condition associated with stillbirth in our setting. Novel findings include 2 classes, distinguished by high placental RPH and maternal HIV, respectively, and the non-emergence of a class distinguished by VUE. Conclusion: The size and content of the latent classes and their similarity/dissimilarity to the more generalized patterns identified previously suggest potential new avenues for investigation and theory development concerning the role of the placenta in stillbirth and the impact of HIV.

Association Between Maternal HIV Stigma Among South Indian Mothers Living with HIV and the CD4 Count of Children Living with HIV

HIV stigma takes a multidimensional toll on a mother’s ability to care for herself and subsequently may impact her ability to care for her child, particularly when mother and child are seroconcordant. A cross-sectional analysis was conducted to examine the association between maternal HIV stigma and child CD4 count in rural India. We assessed 108 mother–child dyads and found that a one-unit increase in community stigma fear decreased child CD4 count by 352 cells (95% CI = − 603, − 102), highlighting the need to develop a better understanding of the consequences of HIV-related stigma on the compounded burden of care in households where mother and child both live with HIV.

Maternal HIV drug resistance is associated with vertical transmission and is prevalent in infected infants

Background We aimed to assess if maternal HIV drug resistance is associated with an increased risk of HIV vertical transmission and to describe the dynamics of drug resistance in HIV-infected infants. Methods A case-control study of PROMISE study participants. “Cases” were mother-infant pairs with HIV vertical transmission during pregnancy or breastfeeding and “controls” were mother-infant pairs without transmission matched 1:3 by delivery date and clinical site. Genotypic HIV drug resistance analyses were performed on mothers’ and their infants’ plasma at or near the time of infant HIV diagnosis. Longitudinal analysis of genotypic resistance was assessed in available specimens from infants, from diagnosis and beyond, including ART initiation and last study visits. Results Our analyses included 85 cases and 255 matched controls. Maternal HIV drug resistance, adjusted for plasma HIV RNA load at infant HIV diagnosis, enrollment CD4 count, and antepartum regimens, was not associated with in utero/peripartum HIV transmission. In contrast, both maternal plasma HIV RNA load and HIV drug resistance were independent risk factors associated with vertical transmission during breastfeeding. Furthermore, HIV drug resistance was selected across infected infants during infancy. Conclusions Maternal HIV drug resistance and maternal viral load were independent risk factors for vertical transmission during breastfeeding, suggesting that nevirapine alone may be insufficient infant prophylaxis against drug-resistant variants in maternal breast milk. These findings support efforts to achieve suppression of HIV replication during pregnancy and suggest that breastfeeding infants may benefit from prophylaxis with a greater barrier to drug resistance than nevirapine alone.

Maternal HIV and syphilis are not syndemic in Brazil: Hot spot analysis of the two epidemics

While the annual incidence of HIV diagnosis in pregnancy in Brazil remains relatively stable, rates of maternal syphilis increased over six-fold in the past decade. We hypothesized that maternal HIV and syphilis are two distinct epidemics. Data on all cases of maternal HIV or syphilis detected in pregnancy between January 1, 2010 to December 31, 2018 were requested from the Brazilian Ministry of Health. In order to evaluate how the epidemics evolved over the time period, ArcGIS software was used to generate spatiotemporal maps of annual rates of detection of maternal HIV and syphilis in 2010 and 2018. We utilized Euclidean-distance hot spot analysis to identify state-specific clusters in 2010 and 2018. From 2010 to 2018, there were 66,631 cases of maternal HIV, 225,451 cases of maternal syphilis, and 150,414 cases of congenital syphilis in Brazil. The state of Rio Grande do Sul had the highest rate of maternal HIV detection in both 2010 and 2018. Hot spots of maternal HIV were identified in the three most Southern states in both 2010 and 2018 (99% confidence, z-score >2.58, p <0.01). While syphilis incidence >30 per 1,000 live births in 2018 in four states, only the two coastal states of Rio de Janeiro and Espirito Santo in Southeastern Brazil were significant hot spots (90% confidence, z-score 1.65–1.95, p <0.10). Contrary to the general assumption, HIV and syphilis epidemics in Brazil are not syndemic in pregnant women. There is a spatial cluster of maternal HIV in the South, while syphilis is increasing throughout the country, more recently on the coast. Focusing on maternal HIV hot spots in the Southern states is insufficient to curtail the maternal and congenital syphilis epidemics throughout the country. New strategies, including ongoing hot spot analysis, are urgently needed to monitor, identify and treat maternal syphilis.

Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study

Background Maternal HIV increases the risk of adverse birth outcomes including preterm birth, fetal growth restriction, and stillbirth, but the biological mechanism(s) underlying this increased risk are not well understood. We hypothesized that maternal HIV may lead to adverse birth outcomes through an imbalance in angiogenic factors involved in the vascular endothelial growth factor (VEGF) signaling pathway. Methods In a case–control study nested within an ongoing cohort in Zambia, our primary outcomes were serum concentrations of VEGF-A, soluble endoglin (sEng), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFLT-1). These were measured in 57 women with HIV (cases) and 57 women without HIV (controls) before 16 gestational weeks. We used the Wilcoxon rank-sum and linear regression controlling for maternal body mass index (BMI) and parity to assess the difference in biomarker concentrations between cases and controls. We also used logistic regression to test for associations between biomarker concentration and adverse pregnancy outcomes (preeclampsia, preterm birth, small for gestational age, stillbirth, and a composite of preterm birth or stillbirth). Results Compared to controls, women with HIV had significantly lower median concentrations of PlGF (7.6 vs 10.2 pg/mL, p = 0.02) and sFLT-1 (1647.9 vs 2055.6 pg/mL, p = 0.04), but these findings were not confirmed in adjusted analysis. PlGF concentration was lower among women who delivered preterm compared to those who delivered at term (6.7 vs 9.6 pg/mL, p = 0.03) and among those who experienced the composite adverse birth outcome (6.2 vs 9.8 pg/mL, p = 0.02). Median sFLT-1 concentration was lower among participants with the composite outcome (1621.0 vs 1945.9 pg/mL, p = 0.04), but the association was not significant in adjusted analysis. sEng was not associated with either adverse birth outcomes or HIV. VEGF-A was undetectable by Luminex in all specimens. Conclusions We present preliminary findings that HIV is associated with a shift in the VEGF signaling pathway in early pregnancy, although adjusted analyses were inconclusive. We confirm an association between angiogenic biomarkers and adverse birth outcomes in our population. Larger studies are needed to further elucidate the role of HIV on placental angiogenesis and adverse birth outcomes.