Thesis (Ph.D.)--University of Washington, 2019Daily, oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is a highly efficacious HIV prevention strategy for key populations at high risk of HIV, including women, in sub-Saharan Africa. However, open-label studies and demonstration projects have reported that young women have difficulty adhering to PrEP over time, which limits its effectiveness as a prevention option. PrEP projects are now exploring modifiable barriers to adherence among women to maximize its public health benefit as it is being rapidly rolled out worldwide. Mental health factors, including depression, traumatic stress symptoms, and stigma, are highly prevalent among women at high risk of HIV acquisition and are barriers to medication use and health promotion behaviors. However, there has been little consideration until now of how such factors might also influence PrEP adherence among women in sub-Saharan Africa. The aims in this dissertation attempt to fill this research gap by: 1) exploring the impact of depressive symptoms on PrEP adherence among women; 2) examining the mechanisms by which depressive symptoms influence PrEP adherence; 3) describing the broader context of HIV-related stigma and empowerment on PrEP use; and 4) integrating depression screening into HIV care delivery to improve mental health and HIV outcomes. Two studies have examined the influence of depression on PrEP adherence and found that depressive symptoms have a negative effect on daily PrEP use for transgender women and men who have sex with men. Ours is the first study to examine links between depression and PrEP adherence among cisgender women in sub-Saharan Africa. We used marginal structural models to estimate the association between depressive symptoms and PrEP adherence while adjusting for time-varying confounding by sexual behavior, stigma, and social support. We found that probable depression was significantly associated with poor PrEP adherence among women, but not men, suggesting that mental health and depression experiences have differential impact on HIV prevention behaviors by gender. This work also led to questions about the mechanism of this association and whether there were important mediators of the relationship between depression and PrEP adherence that could explain at least some of this total effect. We conducted a mediation analysis using marginal structural models to estimate the controlled direct effect of depression on PrEP adherence, after accounting for the potentially mediating influence of HIV-related stigma, social support, and optimism about PrEP effectiveness. We found a significant negative direct influence of depression on PrEP adherence but this relationship was not strongly mediated by other psychosocial factors. Future research is needed to explore additional potential mediators of this relationship and identify areas for intervention. Qualitative research methods allow us to explore narratives around PrEP use, experiences of stigma, and concerns about mental health that are not captured by quantitative data. We analyzed serial in-depth interview data from a cohort of young women using PrEP to understand the broader context around their pill-taking, mental health, and relationships. In this study, we found that women described experiences of HIV-related stigma when they began taking PrEP which influenced their ability to take PrEP and their feelings about themselves. However, over time, women became more empowered to use PrEP and combat HIV-related stigma by becoming “ambassadors” of PrEP in their communities. This work highlights the potential for empowerment-based interventions to improve PrEP adherence and reduce community stigma and the richness of serially collected qualitative data. In Aims 1-3, we found evidence of a strong negative impact of depression on PrEP adherence and high rates of depression among women at risk of HIV. This work suggests that integrated depression screening and treatment with HIV prevention service delivery could improve mental health outcomes and PrEP effectiveness for women. To support the design of future integrated interventions, we conducted cognitive interviews assessing comprehensibility and acceptability of a widely used depression screening tool in the context of a PrEP delivery intervention among pregnant and postpartum women in Thika, Kenya. We found that the tool was largely acceptable and well-understood, but several minor changes to item wording and instructions would improve symptom screening and linkage to mental health care. These changes are part of our recommendations for the future use of this tool. The collective results presented in this dissertation illustrate the negative influence of depression and related psychosocial factors on consistent PrEP use for women, opportunities for stigma-reduction and empowerment-based intervention approaches to improve mental health symptoms and PrEP use in this population, and the potential to administer depression screening within the context of HIV prevention service delivery. This work contributes to a better understanding of the links between mental health and HIV risk for women and highlights the importance of integrating mental health and empowerment-based interventions with PrEP delivery to improve mental health screening and treatment and PrEP effectiveness for women in sub-Saharan Africa
