FAMILY MATTERS: Relationship dynamics among couples affected by HIV during pregnancy, and neurodevelopment of HIV-exposed uninfected infants in sub-Saharan Africa

Relationship dynamics among couples affected by HIV during pregnancy, and neurodevelopment of HIV-exposed uninfected infants in sub-Saharan Africa Michelle A Bulterys Chair of the Supervisory Committee:Dr. Grace John-Stewart Departments of Epidemiology, Global Health and Pediatrics Introduction: Caregiver wellbeing is closely linked to child health and neurodevelopmental outcomes. Families affected by HIV in sub-Saharan Africa (SSA) may face increased risk of poverty, parental relationship dissolution, and poorer child neurodevelopment, but these associations are poorly understood. Pregnant women living with HIV (PWLHIV) in sub-Saharan Africa (SSA) are especially vulnerable to adverse consequences of disclosure of their HIV serostatus, including separation, financial hardship, and poor mental and physical health outcomes. The integration of quantitative and qualitative research methods is urgently needed to better understand the predictors and consequences of separation among couples affected by HIV. Perinatal HIV exposure can increase risk of neurodevelopmental delay in children, irrespective of child HIV acquisition. Thanks to remarkable strides in prevention of mother-to-child transmission (PMTCT), there are now nearly 16 million children who are HIV-exposed uninfected (CHEU), with an additional one million CHEU born every year in SSA. It is crucial to identify caregiver-related factors associated with child neurodevelopment to ensure CHEU thrive in a manner comparable to their HIV-unexposed peers. Methods: This dissertation aimed (Chapter I) to identify factors associated with relationship dissolution between Ugandan PWLHIV and their male partners among couples enrolled in a randomized clinical trial and recommend strategies to increase male partner testing and knowledge of HIV serostatus, employing mixed methods using a convergent parallel design, (Chapter II) to compare one-year neurodevelopment between Kenyan children with and without perinatal HIV exposure in a prospective longitudinal cohort, and identify caregiver factors associated with poor child neurodevelopment using multivariate linear mixed effects models, and (Chapter III) to synthesize latest literature in a commentary about the biologic and social mechanisms through which maternal HIV could impact child neurodevelopment, and to suggest research and advocacy directions to fill knowledge gaps for CHEU. Results: (Chapter I) Separation during pregnancy and postpartum was frequent (23%) among the 500 pregnant Ugandan women living with HIV, and was associated with being in unmarried, non-cohabitating, shorter relationship duration (<1 year), polygamous relationships, as well as HIV non-disclosure and experience of verbal abuse. Participants discussed how HIV serodifferent status, financial burdens, and strong gender expectations led to relationship conflict. Separation was discussed as both a negative and positive outcome depending on couples’ circumstances, in terms of mental health, treatment continuation, financial security, and experience with IPV. (Chapter II) At one-year evaluation among Kenyan infants, CHUU (N=715) and CHEU (N=416) had comparable neurodevelopment scores across all tested domains. Among all children, after adjusting for confounders selected a priori and clustering by site, lower child neurodevelopment scores were significantly associated with male sex, having a deceased or absent father, and maternal report of IPV. Among CHEU, in utero exposure to efavirenz (EFV)-based regimens during pregnancy was associated with lower gross motor scores compared to DTG-based regimens. (Chapter III) Latest evidence from a scoping literature review suggests that perinatal HIV and ART exposure can biologically influence child neurodevelopment through altered immune function, structural brain integrity, systemic inflammation, and growth faltering. There are limited data on the roles that social and behavioral factors play in promoting child neurodevelopment among families affected by HIV in SSA. Conclusion: Relationship dissolution commonly occurs among couples affected by HIV, for a myriad of reasons. It is imperative to improve counseling messaging and better support people living with HIV who may experience IPV, relationship conflict, and separation from their partners, particularly during the vulnerable periods of pregnancy and postpartum. Additionally, IPV and paternal absence in the first year of life were significantly associated with poorer child neurodevelopment, regardless of maternal HIV status, and will require harmonized approaches to address and mitigate risk of delays. Despite evidence that CHEU have unique biologic and social factors that may influence their brain maturation, immune system, and overall health and wellbeing, we did not find a statistically significant difference in 1-year neurodevelopment between CHEU and CHUU. The lack of neurodevelopmental difference between CHEU and CHUU in this cohort, despite several sociodemographic differences, could be potentially attributable to the wider spread and more prolonged use of newer maternal DTG-based ART regimens during pregnancy and breastfeeding; prior studies have been unable to assess these improved regimens which are better able to sustain viral suppression and improve maternal health, so additional research is needed to validate this finding. There is an urgent need for rigorous, multidisciplinary research to identify modifiable aspects of biologic and household exposures that impact child neurodevelopment, as well as clear referral pathways for children, caregivers, and providers in need of additional support.