The THRIVE Study: Protocol for a longitudinal case-control study on the role of stress and genital immunity in sexual trauma and HIV susceptibility among adolescent girls and adult women (Preprint)

BACKGROUND The relationship between sexual violence and HIV risk has been extensively documented through social and behavioral research; by contrast, the explanatory underlying biological mechanisms are poorly understood. OBJECTIVE The purpose of the THRIVE Study is to examine the impact of sexual trauma due to sexual violence on HIV susceptibility through dysregulation of: (a) soluble inflammatory and anti-inflammatory/anti-HIV biomarkers in the female genital tract and (b) the hypothalamic-pituitary-adrenal axis, among adolescent girls and adult women. METHODS The THRIVE study is a longitudinal case-control study conducted in San Diego, California, USA among a racially diverse sample. Cases are adolescent girls (aged 14-19) or adult women (aged 20-45) who have experienced forced vaginal penetration perpetrated by a male within the past 15 days. Controls are adolescent girls or adult women who have engaged in consensual vaginal sex with a male within the past 15 days. At baseline, 1- and 3-month follow-up study visits, participants undergo: (1) a urine-based pregnancy test, (2) venipuncture blood draw for HIV, C-reactive protein, adrenocorticotropic hormone and progesterone testing, (3) a 45-minute interviewer-administered computer survey, and (4) cervicovaginal lavage to measure pro-inflammatory and anti-inflammatory/anti-HIV soluble immune biomarkers. After each study visit, participants self-collect saliva specimens (upon waking, 30-minutes post-waking, and 45-minutes post-waking) at home for three consecutive days, which is later assayed for cortisol and dehydroepiandrosterone sulfate. Participants receive compensation at each study visit and for the return of saliva specimens, plus a list of local medical and support services. Study procedures utilize trauma-informed care methods, given the sensitive nature of the study and enrollment of women in the acute phase post-sexual trauma. All research staff and investigators adhere to ethical principles and guidelines in the conduct of research activities. Data will be analyzed for descriptive and inferential analysis. RESULTS Presently, recruitment of participants is ongoing. Publication of first results is expected by late 2021. CONCLUSIONS The THRIVE Study will deliver foundational knowledge on how sexual trauma due to sexual violence increases susceptibility to HIV acquisition via alterations in cervicovaginal immune regulation and the psychobiology of the stress responses. Findings will inform future research on mechanistic models of in-vitro and in-vivo injury and cervicovaginal wound healing processes, which may lead to non-vaccine biomedical HIV prevention products for girls and women. CLINICALTRIAL