Prevention and pathogenesis of vertically acquired HIV infection in a high-income setting

• Author / Creator

  Choudhury, Bipasha

• Background

  Human immunodeficiency virus (HIV) continues to be a major public health issue globally. An estimated 150,000 infants are infected annually through vertical transmission (VT). The prevention of vertical transmission of HIV can be mitigated through HIV screening in pregnancy; however, prevention remains challenging for mothers who seroconvert after the antenatal screening, later in pregnancy, or while breastfeeding. Despite public health interventions, VT, although rare, continues to occur in these groups and may be difficult to prevent entirely with current strategies. Moreover, children living with HIV (CLWH) face lifelong exposure to HIV and may be at risk of developing premature cardiovascular disease (CVD) despite achieving viral suppression with combination antiretroviral therapy (cART).
  Endothelial activation is one mechanism that may increase the risk of CVD.

  This thesis has two objectives: (1) to describe pregnancy outcomes and the prevalence of risk factors for HIV transmission in HIV-serodiscordant couples (chapter 2); and (2) to examine the correlation between markers of the pathologic pathways involved in endothelial activation in CLWH (chapter 3).

  Methods

  In chapter 2, we report a case of maternal primary HIV infection during the postpartum period and VT to a nursing infant in our high-income setting. We then document a case series of 47 serodiscordant pregnant couples identified through a nurse-led public health program to follow HIV serodiscordant couples.

  In chapter 3, we present the results of a cross-sectional study with the measurement of selected biomarkers of microbial translocation, systemic inflammation, and endothelial activation in the Early Pediatric Initiation-Canadian Child Cure Cohort (EPIC4), a well-characterized cohort of CLWH across Canada with detailed longitudinal clinical and laboratory data.

  Results

  In chapter 2, we found that no cases of HIV seroconversion occurred in 47 HIV-serodiscordant couples. However, high viral load (VL) among some seropositive males was observed during the period of pregnancy and breastfeeding. Among HIV-infected male partners, 15 had a detectable viral load (VL) during their partner’s pregnancy, with median (IQR) peak VL of 3,800 (IQR 370-14,000) copies/mL, and 16 males had a detectable VL during breastfeeding, with median (IQR) peak VL was 5,000 (210-30,000).

  In chapter 3, in a sample of 90 CLWH, we found that 16% of Angiopoietin-2 (Ang2), 15% of soluble vascular endothelial growth factor-1 (sVEGFR1), and 23% of soluble endoglin (sEng) levels were elevated relative to healthy historic controls. Pairwise rank-correlations between the three markers of endothelial activation were statistically significant (ρ = 0.69, ρ = 0.61, and ρ = 0.65, p<0.001 for all correlations respectively). An endothelial activation index (EAI), derived by factor analysis of the three endothelial biomarkers, correlated with inflammatory markers tumor necrosis factor (TNF, ρ = 0.47, p<0.001) and interleukin-6 (IL-6, ρ = 0.60, p<0.001). The EAI also correlated with a marker of gut barrier injury, intestinal fatty acid-binding protein (I-FABP1, ρ = 0.67, p<0.001). Current or past treatment with ritonavir-boosted lopinavir (LPV/r) was associated with endothelial activation (OR 5.0 (95%CI 1.7-17), p=0.0020).

  Conclusions

  This thesis addresses VT of HIV in a high-risk group (serodiscordant couples) and one of its consequences for CLWH (endothelial activation). These findings may contribute to continuing efforts to eliminate VT of HIV in Canada and may help understand and prevent long-term cardiovascular complications in CLWH.

• Subjects / Keywords

  • HIV in high-income setting

• Graduation date

  Fall 2020

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-74xm-vc34

• License

  Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.